2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650

Nuclear Medicine and Biology,
August 2014, Volume 41, Issue 7, Pages 545‐650
Abstracts for Symposium on Technetium and
Other Radiometals in Chemistry and Medicine
(TERACHEM 2014), September 10‐13, 2014

14.10.2014 Nuclear Medicine and Biology, August 2014, Volume 41, Issue 7, Pages 545-650
11
Human whole-body biodistribution and dosimetry of a new PET tracer, [ C]ketoprofen methyl
ester, for imagings of neuroinflammation
Akihito Ohnishi, Michio Senda, Tomohiko Yamane, Masahiro Sasaki, Tomoko Mikami, Tomoyuki
Nishio, Yasuhiko Ikari, Hiroyuki Nishida, Miho Shukuri, Tadayuki Takashima, Aya Mawatari, Hisashi
Doi, Yasuyoshi Watanabe, Hirotaka Onoe
p594–599
Published online: April 14, 2014
Preview Abstract Full-Text HTML PDF
99m 3
A study on nitroimidazole- Tc(CO) complexes as hypoxia marker: Some observations
towards possible improvement in in vivo efficacy
Madhava B. Mallia, Suresh Subramanian, Anupam Mathur, H.D. Sarma, Sharmila Banerjee
p600–610
Published online: April 24, 2014
“The quantification with FDG as seen by a physician.” Nucl Med Biol 2013;40:720–30
Luigi Mansi
p611–612
Published online: May 1, 2014
Abstracts for Symposium on Technetium and Other Radiometals in Chemistry and Medicine
(TERACHEM 2014), September 10-13, 2014
Organometallic technetium chemistry; past, present and future
Roger Alberto, Henrik Braband, Michael Benz, Michael Felber, Sebastian Imstepf
p613
Hide Preview Abstract Full-Text HTML PDF
Routinely applied, metallodrugs are coordination compounds and rarely of organometallic nature, Cardiolite® being
the most mentionable exception. Over the last decade, bioorganometallic chemistry grew to a prosperous field to
which Tc and Re chemistry contributed essential results [1]. The “aquo-ion” [ 99m
Tc(OH ) (CO) ] +
2 3 3
opened a realm of
chemistry, fundamental and imaging oriented and in line with the concepts of bioorganometallic chemistry of stable
elements. Contributions of many groups, in support of this statement, will be highlighted.
99(m) 3 + 99(m) 4 −
Synthesis of fac-{ TcO } complexes: Activation of [ TcO ] by phosphonium cations
Henrik Braband, Michael Benz, Roger Alberto
p613
X
http://www.nucmedbio.com/issue/S0969-8051(13)X0014-9 3/14

The reaction of high-valent fac-{ 99m
TcO +
3
} complexes with alkenes via (3 + 2)-cycloaddition is an innovative
approach for the synthesis of radioconjugates [1-3]. Recent developments, based on the interaction of
phosphonium salts with the robust [ 99(m)
TcO 4
] −
anion in neutral water, led to a simple procedure for the synthesis of
[ 99m
TcO (tacnR)] +
3
type complexes (tacnR = 1,4,7-triazacyclononane or derivatives). Due to this new approach fac-
{ 99m
TcO } complexes are now available in high yields and purity for stereoselective labeling of biomolecules.
3
+
99m 111
Imaging carbon nanotube-mediated drug delivery with Tc and In
Sam Groveman, Simone Alidori, Lynn Francesconi, David A. Scheinberg, Michael R. McDevitt
p613–614
Carbon nanotubes (CNT) are potentially versatile drug delivery platforms due to their large aspect ratio which
allows for amplification of drug and imaging effects. Furthermore, this nanomaterial exhibits distinctive fibrillar
pharmacology. When covalently functionalized, CNT can accommodate a numerous amount of different molecular
components designed for theranostic purposes. It was demonstrated that antibodies, peptides, oligonucleotides,
and other drugs can be appended covalently and non-covalently to CNT.
Higher carbonyl cores of Tc and Re bioconjugates: Prospects and limitations
A.E. Miroslavov, G.V. Sidorenko, A.A. Lumpov, M.Yu. Tyupina, D.N. Suglobov
p614
Although [M(CO) + 99m 186,188
3 (H 2 O) 3
] cations (M = Tc or Re) are convenient precursors for tethering Tc or Re to
biomolecules, introduction of M(CO) 3
core into a biomolecule requires bulky tridentate chelators or a combination of
mono- and bidentate coordination units, which can negatively affect the native properties of the biomolecule. To
minimize this influence, we suggested technetium and rhenium penta- and tetracarbonyl cores in combination with
mono- (isocyanide) and bidentate (dithiocarbamate, xanthate) ligating units, respectively.
99m
Synthesis and biological evaluation of TcO-MNXT as a novel tumor hypoxia imaging agent
Zhenxiang Li, Xuebin Wang, Junbo Zhang
p614
In the development of hypoxia imaging agents, nitroimidazole derivatives are enzymatically reduced and
accumulated in hypoxic regions, therefore most labeled probes for tumor hypoxia have been based on
nitroimidazole analogues. In order to find a novel ideal hypoxia imaging agent, MNXT (metronidazole xanthate) was
synthesized and radiolabeled with 99m Tc-GH to form the 99m
TcO–MNXT complex. The radiochemical purity of the
TcO–MNXT complex was over 90%, as measured by TLC. It was stable over 6 h at room temperature.
99m
99m
X
X
X
X

3 99m
[CpM(CO) ] (M = Re, Tc) labeled phenylbenzothiazoles as imaging agents for Aβ plaques
Jianhua Jia, Mengchao Cui, Boli Liu
p614
99m
The complexes of [CpM(CO) 3
] (M = Re, Tc) conjugating the phenylbenzothiazole were synthesized and
evaluated to detect amyloid-β (Aβ) deposition in the brain. The rhenium complexes 1–4 were proved to have
medium affinity for Aβ aggregates (K = 142, 76, 64 and 24 nM, respectively) by in vitro binding assays. 99m
1–42 i
Tc
complexes clearly marked Aβ plaques on brain sections of Tg mice by in vitro autoradiography, which confirmed the
sufficient affinities for Aβ plaques (Fig. 1). However, they did not show admirable property in respect of initial brain
uptake (<0.5% ID/g), which hinders the further development of these tracers as SPECT probes for diagnosis of AD.
Synthesis and evaluation of single amino acid chelate (SAAC) tetrazine derivatives for
bioorthogonal conjugation with Re/ 99m
Tc
John F. Valliant, Ramesh Patel, Alyssa Vito
p614–615
The inverse electron demand [4 + 2] Diels–Alder cycloaddition reaction between radiolabeled 1,2,4,5-tetrazines and
biomolecule-derived strained alkenes has recently been used to create molecular imaging probes that generate
exquisite target-to-non-target ratios [1]. The advantage of this pretargeting strategy is that short-lived radioisotopes
can be used to image the distribution of biomolecules such as antibodies that have slow pharmacokinetics. The
work to be presented involves the preparation of isostructural 99m
Tc and Re complexes of ligands derivatized with
tetrazines which can be used to tag trans-cyclooctene modified biomolecules.
3 99m
Enhancing chemical properties and stability of M(CO) (M = Re, Tc) complexes through
ligand donor modifications
Paul D. Benny, Thomas R. Hayes, Patrice A. Lyon
p615
While a number of chelates and strategies have been developed for the organometallic precursor fac-
[M(OH ) + 99m
2 3 (CO) 3
] (M = Re, Tc), a unique challenge remains to improve the overall function and performance of
these complexes formed for in vitro and in vivo applications. The versatile nature of the M(CO) +
3
core resides in the
facile preparation and exchange of the aquo ligands with mono-, bi- or tridentate ligands. However, the overall
stability and lipophilic nature of the CO ligands inherently impact the pharmacodynamic behavior and in vivo
clearance properties of M(CO) complexes.
3
(V) 2 + 99
Synthesis of water stable {M O } -N-heterocyclic carbene complexes (M = Re, Tc)
Michael Benz, Henrik Braband, Roger Alberto
p615
X
X
X

Recently, the scope of N-heterocyclic carbenes (NHCs) has been extended from catalytic application to the field of
bioinorganic chemistry and metals in medicine. In this context, the NHC chemistry of technetium came into our
research focus. However, 99 Tc–NHC complexes are scarce [1]. While {Re (V)
O } +
2
complexes, which contain
monodentate NHCs, are hydrolytically stable, the corresponding {Tc (V)
O 2
} +
–NHC complexes show rapid hydrolysis
in the presence of trace amounts of H 2
O [2]. We present novel synthetic pathways for the synthesis of water stable
{M (V)
O } –NHC complexes [3].
2
+
Tc-labelling of surface localised SNAP-tag sites on a Gram positive bacterium
99m
Ramla Awais, Bethany Mills, Jeni Luckett, Paul Williams, Phil Hill, Alan Perkins, Philip Duncanson,
Vaughan Griffiths
p615
6
SNAP-tag is a protein based on human O -alkylguanine-DNA alkyltransferase (hAGT) that can bind specifically and
covalently to substrates bearing an O 6
-benzylguanine unit. It has proved possible to express this protein in the
Gram positive bacteria Staphylococcus aureus and to specifically anchor it to the bacterial cell wall via Sortase A,
thus providing a potential strategy for selectively labelling these modified bacteria. As preliminary data showed that
the surface-localized SNAP tags are accessible to fluorescent probes bearing an O 6
-benzylguanine unit in vitro we
have investigated the possibility of developing analogous radioligands.
Tc-labeled biotin conjugate in a tumor “pretargeting” approach with monoclonal antibody
99m
bevacizumab
N. Kiza, G. Makris, D. Papagiannopoulou, T. Tsotakos, D. Mastellos, C. Tsoukalas, P. Bouziotis
p615–616
Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor
angiogenesis. Bevacizumab is designed to directly bind to VEGF extracellulary to prevent interaction with VEGF
receptors. Given the drawbacks of radiolabeled monoclonal antibodies (mAbs) such as slow blood clearance and
unspecific binding to normal tissues, antibody pretargeting is an approach which combines the desirable properties
of high tumor uptake of antibodies with rapid pharmacokinetics and fast whole-body clearance of radioactivity.
99m
Characterization of Tc-caspofungin as fungal infection agent and assessment of potential
influence of pretreatment
Laura Reyes, Leticia Fernández, Mónica Vilche, Patricia Oliver, Ana Rey, Mariella Terán
p616
Reliable clinical interpretation of scintigraphic images for the diagnosis of fungal infections is not always simple
because of low specificity and sensitivity of the available radiopharmaceuticals [1]. Our group studies potential
99m
X
X
X
X

99m
99m
radiopharmaceuticals for infection diagnosis, in this particular case characterization of Tc–caspofungin–
tricarbonyl complex and the influence of pretreatment with caspofungin is evaluated. Tc–caspofungin–tricarbonyl
complex was obtained by water molecules substitution of fac-[Tc(I)(H 2 O) 3 (CO) 3
] +
precursor with caspofungin
(MERCK) [2].
99m
Imidazole stabilized [2 + 1] Re(I)/ Tc(I) complexes as isostructural nuclear and optical probes
Abdolreza Yazdani, Tamil Selvi Pitchunmony, Laura Banevicius, Shannon Czorny, John F. Valliant
p616
The synthesis, stability and photophysical properties of [2 + 1] Re(I)/Tc(I) complexes of bipyridine and a series of
triazole and imidazole derivatives were investigated as a means of identifying complexes suitable for use in creating
targeted isostructural optical/nuclear molecular imaging probes. To prepare the desired complexes,
[Re(CO) 3 (H +
2 O) 3
] was combined with 2,2′-bipyridine (bipy) to give [Re(CO) 3
(bipy)Br] which in turn was converted to
the desired complexes through the treatment with functionalized triazoles and imidazoles and heating the mixture to
reflux overnight.
Labelling PAMAM dendrimers with Tc-99m via HYNIC
L. Kovacs, M. Tassano, M. Cabrera, M. Fernández, R. Anjos, P. Cabral, W. Porcal
p616–617
Dendrimers are branched macromolecules with a well-defined structure, very low polydispersity and high
functionality. Poly(amidoamine) (PAMAM) dendrimers are the most studied class of dendrimers for biomedical
purposes. In the present study, PAMAM G4 dendrimer conjugated with hydrazinonicotinamide (HYNIC), an efficient
bifunctional chelator, was characterized and optimized. The conjugated dendrimer was labeled with 99m
Tc using
tricine coligand and the stability of the labeled complex was evaluated.
188
Re radiotherapy facilitated by virus expressing the human sodium iodide symporter
Justin Ady, Justin Belin, Sam Groveman, Yuman Fong, Lynn Francesoni
p617
Rhenium-188 emits a beta with a maximum energy of 2.12 MeV, and can be easily and relatively inexpensively
obtained from portable 188 W/ 188 Re generators as sodium perrhenate (Na 188
ReO 4
). This makes rhenium an
attractive option for use in radio-cancer therapies. The human sodium iodide symporter (hNIS) transports NaI
across cell membranes, but it has been shown that hNIS can also transport perrhenate (ReO −
4
). hNIS, which is
expressed primarily in the thyroid glands, has facilitated radiotherapy for thyroid cancer for over sixty years.
99m
Determination of optimized conditions for Tc-labeled rifampicin preparation for
tuberculosis imaging applications
X
X
X

Ali Badbarin, Amir R. Jalilian, Fariba Johari Daha, Mitra Athari-Alaf
p617
Developing new infection imaging agents is a mandate in the detection of resistant species in the clinic due to the
mortality of various new strains of bacteria including Mycobacterium tuberculosis. Various conditions were
optimized for the rapid and efficient labeling of rifampicin antibiotic with Tc-99m for ultimate use in infection imaging.
Radiochemical purities were checked by ITLC using methyl ethyl ketone, normal saline on Whatman No. 1 paper.
Time, temperature, ligand concentration, stannous ion amount, pH etc.
99m
Novel Tc-labelled estrogen derivative as potential agent for estrogen receptors imaging
L. Bauzán, S. Fernández, S. Dematteis, H. Cerecetto, J. Giglio, A. Rey
p617
With the objective to develop a potential radiopharmaceutical for estrogen receptors imaging we have prepared and
evaluated an ethinylestradiol derivative labelled with 99mTc.
99m
[ Tc(N)PNP]-scaffold for SPECT of multidrug resistance: Early in-vitro study
C. Bolzati, V. Gandin, N. Morellato, N. Salvarese, C. Marzano, D. Carpanese, L. Meléndez-Alafort, A.
Rosato
p618
Tc(N)-DBODC(PNP5) [DBODC = bis(N-ethoxyethyl)dithiocarbamato; PNP5 =
99m
bis(dimethoxypropylphosphinoethyl)ethoxyethylamine] is a cationic mixed-compound, originally investigated as
myocardial imaging agent, identified as suitable scaffold to devise 99m
Tc-agents for SPECT of multidrug resistance
(MDR).
99m
Aptamer-HYNIC- Tc: A molecular imaging agent of PTK7
Victoria Calzada, Marcelo Fernández, Joel González, María Moreno, Alejandro Chabalgoity, Hugo
Cerecetto, Pablo Cabral, Thomas Quinn
p618
Aptamers are single-stranded oligonucleotides that recognize molecular targets with high affinity and specificity.
The unique molecular recognition properties of aptamers are being developed to image protein tyrosine kinase-7
(PTK7), a member of the receptor tyrosine kinase family, over expressed on many cancers. In this work, a DNA
aptamer against PTK7 was coupled with HYNIC(Tricine) and radiolabeled with technetium-99m. Physicochemical
and biological controls were assayed in acute lymphoblastic leukemia CCRF-CEM cells.
X
X
X
X

Thiocarbamoylbenzamidines for bioconjugation of Re and Tc
Juan Daniel Castillo Gómez, Nguyen Hung Huy, Ulrich Abram, Nicola Beindorff, Winfried Brenner
p618
Thiocarbamoylbenzamidines are suitable ligand systems for Re and Tc [1,2]. However, no studies regarding their
suitability for bioconjugation with 99m
Tc have been published so far. We have designed different complexes of Re
and 99
Tc with thiocarbamoylbenzamidines, which possess propargylic or carboxylic groups available for
bioconjugation. 1
H-NMR studies of the click-coupling products with model molecules show the disappearance of the
propargylic signal and the formation of the triazole ring as confirmed by X-Ray crystal analysis.
99m
Biological evaluation of two glucose derivatives radiolabeled with Tc as potential cancer
imaging agents
Rosina Dapueto, Marcelo Fernández, Rodrigo Aguiar, María Moreno, Camila Machado, Fabio
Marques, Juan P. Gambini, Roger Chammas, Pablo Cabral, Williams Porcal
p618–619
99m 18
The aim of this work is to develop two glucose derivatives radiolabeled with Tc in order to obtain FDG analogs
for SPECT. Both derivatives were designed to contain an IDA-like chelator for complexation with 99m
Tc attached to
glucose anomeric carbon (C1) or C2. Radiolabeling with 99m
Tc of compounds was accomplished by direct labeling
with high radiochemical purity controlled by HPLC. Complexes also probed to be highly stable in time until 5 hours
of radiolabeling and hydrophilic according to LogP values.
99m 2 3 3 +
Radiolabeling and biological evaluation of amphotericin using fac-[ Tc(I)(H O) (CO) ]
Leticia Fernández, Laura Reyes, Mariella Terán
p619
Mycoses are fungal infections that usually do not cause serious illness; nevertheless severe immunosuppression
may compromise the patient's life. Infection identification and its discrimination from inflammation are a challenging
dilemma. The implications of prompt diagnosis on the appropriate management of infectious foci's are vital for the
patient's evolution. Nuclear medicine can be an alternative using a suitable radiotracer to detect infection sites [1].
99m
Development of a Tc(I)-tricarbonyl complex as potential agent for hypoxia imaging
S. Fernández, J. Gigio, H. Cerecetto, A. Rey
p619
99m
Herein, we present the development of a Tc complex bearing the 5-nitroimidazol-1-yl moiety, with recognized
hypoxic selectivity, as a potential radiopharmaceutical for imaging tumour hypoxia.
X
X
X
X

A novel Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptide with enhanced melanoma
uptake
Haixun Guo, Yubin Miao
p619
The purpose of this study was to examine the melanoma targeting and imaging properties of 99m
Tc-labeled lactam
bridge-cyclized HYNIC-Aoc-Nle-CycMSH hex
{hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-
Arg-Trp-Lys]-CONH 2 } peptide. Methods: HYNIC-Aoc-Nle-CycMSH hex
was synthesized using fluorenylmethyloxy
carbonyl (Fmoc) chemistry. The melanocortin-1 (MC1) receptor binding affinities of the peptide were determined in
B16/F1 melanoma cells. The melanoma targeting and imaging properties of 99m
Tc(EDDA)-HYNIC-AocNle-
CycMSH were determined in B16/F1 melanoma-bearing C57 mice.
hex
99m
Synthesis and preliminary evaluation of Tc-labelled monomeric, dimeric and tetrameric
folate derivatives
Zhide Guo, Manli Song, Pu Zhang, Chang Liu, Xianzhong Zhang
p620
The aim of this study is to develop a new strategy for developing multimeric molecule probes used for SPECT
imaging. Thus, multimeric concept has been used to synthesise FR-targeting imaging probes (monomeric, dimeric
and tetrameric folate derivatives). The novel folate derivatives were radiolabelled with 99m
Tc using tricine and
trisodium triphenylphosphine-3,3′,3″-trisulfonate (TPPTS) as coligands, and resulted in three 99m
Tc-complexes
( 99m
Tc-HYNIC-D -PEG-FA , Tc-HYNIC-D -PEG-FA , Tc-HYNIC-D -PEG-FA ).
0 1
99m
1 2
99m
2 4
Theoretical study of Re and Tc DMSA complexes
Daniel Hernández-Valdés, Alejandro Blanco-González, Zalua Rodríguez-Riera, Ulises Jaúregui-Haza,
Luis Ducat-Pages, Luis Pizarro-Lou
p620
Meso-2,3-dimercaptosuccinic acid (DMSA) is used in nuclear medicine as ligand for the preparation of
radiopharmaceuticals for diagnostic and therapy. DMSA has been the subject of numerous investigations during the
past three decades and lots of new and significant information on the chemistry and pharmacology of DMSA
complexes have emerged. In comparison to other ligands the structure of many DMSA complexes is unclear up to
today. The structures and applications of DMSA complexes are strictly dependent on the chemical conditions of
their preparation, especially pH and the ratio of components.
Computational study of Re and Tc tricarbonyl complexes
Daniel Hernández Valdés, Zalua Rodríguez Riera, Ulises Jáuregui Haza, Claude Picard, Eric Benoist
p620
X
X
X

The development of novel radiopharmaceuticals in nuclear medicine based on the M(CO) 3
(M = Tc, Re) complexes
has attracted great attention. The versatility of this core and the easy production of the fac-[M(CO) (H O) ]
+
3 2 3
precursor could explain this interest. The main characteristics of these carbonyl complexes are a high substitution
stability of the three CO ligands and a corresponding lability of the coordinated water molecules, yielding, via easy
exchange of a variety of mono-, bi-, and tridentate ligands, complexes of very high kinetic stability.
99m
Preparation and biological evaluation of a Tc labelled fibroblast activation protein inhibitor
P. Iveson, R. Ahmad, M. Bapat, M. Morrison, A. Olsson, A. Meijer
p620
99m
The synthesis, Tc labelling and biological evaluation of a tetraamine derivatised fibroblast activation protein
(FAP) inhibitor (GEH200200) are reported. In vitro studies using the analogous rhenium complex showed good
affinity for FAP (IC 9 mM) and >3000 selectivity for FAP over DPP-IV. 99m
50
Tc-GEH200200 was formed rapidly in
high yield at room temperature. HPLC purified 99m
Tc-GEH200200 was used for in vivo studies in naïve rats.
Metabolism studies showed that 80% of the parent 99m
Tc-GEH200200 was still present in plasma at 60 min p.i.
99m 3
Tc(CO) -labeled 2-phenylbenzothiazoles as Aβ imaging agents for the detection of CAA
Jianhua Jia, Mengchao Cui, Boli Liu
p620–621
Cerebral amyloid angiopathy (CAA) is related to the deposition of β-amyloid (Aβ) on blood vessel walls of brain. To
specifically detect Aβ in CAA, 99m
Tc/Re complexes were prepared and evaluated. 24 displayed high affinity for Aβ
aggregates (K i
= 42 nM). The high affinity of [ 99m
Tc]24 for Aβ was certified by in vitro autoradiography on brain
sections of Tg and AD. Interestingly, [ 99m
Tc]24 could only label Aβ in blood vessels (white triangle) but not Aβ in
parenchyma (gray arrow) of the AD brain (Fig.
99m
Synthesis and biodistribution of TcO-TRYDTC as a novel potential tumor imaging agent
Jingjing Zhu, Qiran Hu, Jin Du, Xuebin Wang, Junbo Zhang
p621
There has been an increasing interest on a wide range of radiolabeled amino acids, because they are the
substrates of various amino acids transport systems, which can be upregulated in certain tumors. L-tyrosine is a
natural amino acid and its molecular structure has an active amine group, thus making it possible to react with
carbon disulfide in NaOH solutions to produce the corresponding dithiocarbamate. In this study, tyrosine
dithiocarbamate (TYRDTC) ligand was successfully synthesized and then radiolabeled with [ 99m TcO] 3+
core to
produce 99m
TcO-TYRDTC with high radiochemical purity.
X
X
X
X

99m 3
Synthesis and biodistribution of Tc(CO) -G12N3 as a potential agent for tumor imaging
Teli Liu, Xuebin Wang, Junbo Zhang
p621
Carbohydrates, especially glucose, are the main energy resource of living beings. It accumulates in some metabolic
vigorous cells and tissues transported by glucose transporters (GLUTs). As for tumor imaging, 99m
Tc labeled
glucose derivatives are considered to be of great interest. In order to get a good tumor imaging agent, we
synthesized a new glucose analogue (G12N3) by ‘click chemistry’ with glucose-azide and alkyne-[12]aneN 3
(a
macrocyclic polyamine). The G12N3 ligand for labeling with 99m Tc through the formation of a 99m
Tc(CO) 3
complex
was successfully synthesized.
99m 3
Synthesis and biodistribution of Tc(CO) -CPADG as a promising tumor imaging agent
Yue Wang, Jingjing Zhu, Xiaoqing Song, Xuebin Wang, Junbo Zhang
p621
18 18
[ F]fluorodeoxyglucose, [ F]FDG, is the most widely used positron emission tomography (PET)
radiopharmaceutical all over the world. However, the high costs related to its production and the need for a
cyclotron nearby are realistic limitations. Therefore, using 99m
Tc to label glucose analogues is still the major focus of
radiopharmaceuticals research. Up to now, the [ 99m
Tc(CO) 3
] +
core has become a valuable alternative to the state of
the art 99m Tc labeling techniques, thus encouraging us to synthesize the 99m
Tc(CO) 3
complex for finding a good
tumor imaging agent.
99m 5
Tc-gastrins: Impact of (Glu) -chain and NEP-inhibition on pharmacokinetics
A. Kaloudi, B.A. Nock, E. Lymperis, E.P. Krenning, M. de Jong, T. Maina
p622
99m 99m 99m
1
Gastrin-based Tc-radiotracers, like [ Tc]SG6 = [( Tc-N 4
)Gln ]gastrin, show higher metabolic stability and
CCK2R-positive tumor targeting compared to des-(Glu) 99m 99m
5
-truncated analogs, such as [ Tc]DG4 = [( Tc-
N 4
)DGlu 10
]gastrin(10–17). However, the (Glu) 5
-chain is implicated in high renal uptake. We herein compare the
effect of neutral endopeptidase (NEP) inhibition by phosphoramidon (PA) on the bioavailability and
pharmacokinetics of [ 99m Tc]SG6 and [ 99m
Tc]DG4 in mice. Blood collected 5 min post-injection (pi) of either
[ 99m Tc]SG6 or [ 99m
Tc]DG4 in mice without or with PA (300 μg) coinjection was analyzed by HPLC.
99m 99m
Imaging of VEGF expression with Tc(I) and Tc(V) bevacizumab conjugates
N. Kiza, C. Tsoukalas, T. Tsotakos, S. Xanthopoulos, M. Paravatou-Petsotas, G. Kastis, P. Bouziotis
p622
X
X
X

Vascular endothelial growth factor (VEGF) is considered to be a major angiogenic factor responsible for the
development of tumor vasculature. 99m
Tc is the most popular radionuclide for clinical imaging because it has ideal
nuclear properties. The aim of this study was to image VEGF expression with 99m
Tc-labeled anti-VEGF antibody
(bevacizumab) non-invasively.
Metastatic melanoma targeting property of a novel Tc-99m-labeled HYNIC-conjugated lactam
bridge-cyclized alpha-MSH peptide
Liqin Liu, Yubin Miao
p622
The purpose of this study was to determine the metastatic melanoma targeting property of the novel 99m
Tc(EDDA)-
HYNIC-AocNle-CycMSH hex
{hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-
CONH 2 } peptide that we have identified. Methods: HYNIC-Aoc-Nle-CycMSH hex
was synthesized using
fluorenylmethyloxy carbonyl (Fmoc) chemistry. The melanocortin-1 (MC1) receptor binding affinities of the peptide
were determined in B16/F10 melanoma cells. The melanoma targeting and imaging properties of 99m
Tc(EDDA)-
HYNIC-AocNle-CycMSH hex
were determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57
mice.
99m
Synthesis and biodistribution of Tc-HYNIC-DG as a novel potential tumor imaging agent
Liqin Liu, Manchen Zhao, Zhuo Wang, Yuanyan Qin, Xuebin Wang
p622–623
In this study, a conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with the D-glucosamine hydrochloride
(DG) was synthesized though a multiple-step reaction. The structure of ligand HYNIC-DG was confirmed by 1
HNMR
and MS. HYNIC-DG could be labeled successfully and efficiently with 99m
Tc using N-[2-hydroxy-1,1-
bis(hydroxymethyl)ethyl]glycine (tricine) and ethylenediamine-N,N′-diacetic acid (EDDA) as co-ligands to form
Tc-HYNIC-DG in high yields (>95%). The partition coefficient and electrophoresis results indicated it was very
99m
hydrophilic and electronegative.
Copolymer based radiotracers for liver ASGP-R targeted SPECT imaging
Chang Liu, Zhide Guo, Pu Zhang, Xianzhong Zhang
p623
Asialoglycoprotein receptor (ASGP-R) is a well-known cell surface receptor specific for liver, present in normal
mammalian hepatocyte membrane. Detection of its number and activity is an excellent method for evaluating the
status and function of liver [1]. Copolymer based radiotracers with controllable ratio of targeting moiety (VLA) were
developed as potential ASGP-R targeted imaging agents. P(VLA-co-VNI) were synthesized by free-radical
copolymerization and lyophilized for Tc instant kit labeling with high yield and 99m RCP (>99%) [2].
X
X
X
X

99m
New GRPR-antagonists mimicking [ Tc]Demobesin 1
T. Maina, A. Nikolopoulou, R. Cescato, D. Charalambidis, B. Waser, E. Ketani, J.C. Reubi, B.A. Nock
p623
99m 99m 99m
We have previously reported on the GRPR-antagonist [ Tc]Demobesin 1, [ Tc]DB1 ( Tc-[N4′-dig-
DPhe 6 ,Leu-NHEt 13
]BBN(6–13)), which shows superior biological profile, and in particular a higher uptake in PC-3
xenografts in mice, than analogous agonist-based 99m
Tc-radioligands. We now present a small library of
[ 99m Tc]DB1 mimics by performing strategic structural modifications in: a) the spacer ([ 99m Tc]DB2, [ 99m
Tc]DB7 and
[ 99m Tc]DB8), b) the C-terminus ([ 99m Tc]DB9 and [ 99m Tc]DB10) and c) the peptide chain ([ 99m
Tc]DB11 and
[ 99m
Tc]DB12).
99m 3 +
New [ Tc(CO) (NSN)] chelate conjugated to a somatostatin receptor-seeking peptide
George Makris, Lauren Radford, Fabio Gallazzi, Silvia Jurisson, Heather Hennkens, Dionysia
Papagiannopoulou
p623
99m
Chelating Tc to a somatostatin receptor (SSTR)-seeking peptide may allow targeted delivery of this attractive
diagnostic radionuclide to neuroendocrine cancers that over-express SSTRs. We present here the synthesis of a
novel tridentate bifunctional chelator, 3-(2-aminoethylthio)-3-(1H-imidazol-4-yl)propanoic acid L, its pyrrolidine
amide derivative Lpyr, and the Lsst 2 -ANT bioconjugate, where the SSTR-seeking peptide sst 2 -ANT (4-NO 2
-Phe-c(
DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH ) is linked to L via the N-terminus.
2
Select All View Abstracts | Export Citations | Email a Colleague | Add to Reading List
1 2 3 Next >
X
X
Copyright © 2014 Elsevier Inc. All rights reserved. | Privacy Policy | Terms & Conditions | About Us | Help & Contact
The content on this site is intended for health professionals.
Advertisements on this site do not constitute a guarantee or endorsement by the journal, Association, or publisher of the quality or value of such product or of the claims made for it by its
manufacturer.

RSS Feeds Mobile
Welcome, Konstantin German
Claim Subscription | Subscribe | My Account | Logout
Articles & Issues For Authors Journal Info SRS Subscribe More Periodicals
All Content Search Advanced Search
Volume 41, Issue 7, p545-650
< Previous Next >
August 2014
Alert me when new issues and articles are available via Email Alert or RSS Feed .
< Prev 1 2 3 Next >
Select All
Search within this issue
View Abstracts | Export Citations | Email a Colleague | Add to Reading List
Browse By Issue
2010 - present
Vol. 41
Issue 7, August 2014, p545-650
List of Issues
Go
Enlarge Cover
99m 3
Synthesis and biological evaluation of novel bone-seeking [Re/ Tc(CO) ] complexes
George Makris, Ioannis Pirmettis, Minas S. Papadopoulos, Dionysia Papagiannopoulou
p623–624
99m 186 188
Radiolabelled bisphosphonates such us Tc-MDP and Re/ Re-ΗΕDP bind to bone matrix carrying γ or β
radiation and are used for bone imaging or bone pain palliation, respectively. In our work we describe the synthesis,
characterization and biological evaluation of novel complexes of the type fac-[Re/ 99m
Tc(CO) 3 3
(κ -L)], Re/ 99m
TcL1,
Re/ 99m TcL2, Re/ 99m
TcL3. Ligands L1–L3 were synthesized by incorporating a different tridentate chelator on the
bone-seeking pharmacophore 1-(3-aminopropylamino)ethane-1,1-diyldiphosphonic acid, di-(2-picolyl)amine in L1,
iminodiacetic acid in L2 and 2-picolylamine-N-acetic acid in L3.
99m
X
http://www.nucmedbio.com/issue/S0969-8051(13)X0014-9?page=1 1/15

99m
New Tc-radioimmunoconjugates for pancreatic carcinoma detection
Laura Meléndez-Alafort, Cristina Bolzati, Gaia Zuccolotto, Giulio Fracasso, Nicola Salvarese, Marco
Colombatti, Antonio Rosato
p624
Pancreas carcinoma is responsible for more than 30% of tumor-related death because it is notoriously difficult to
diagnose; thus, new diagnostic approaches are imperatively needed. Recently, prostate stem cell antigen (PSCA)
and mesothelin demonstrated high expression and wide distribution in pancreatic cancer, but not in normal
pancreas. This research aims to develop new radioimmunoconjugates (RICs) for pancreatic cancer detection based
on monoclonal antibodies (mAb) to PSCA and mesothelin, which are heavily overexpressed in this tumor histotype.
Development and preliminary biological study of radiopharmaceutical for radiosynovectomy
labelled by 188
Re
O.E. Klementyeva, A.O. Malysheva, G.E. Kodina, N.A. Taratonenkova, M.V. Zhukova
p624
Radiosynovectomy is a therapy used to relieve pain and inflammation from rheumatoid arthritis and related
diseases. Progression of the disease leads to the destruction of the joint or loss of function. In this study the 188
Re-
Sn suspension was synthesized and characterized according to its physico-chemical properties and biological
behavior in rabbits.
Synthesis of novel rhenium and technetium N 2 O 2
schiff base complexes
K.M. Reinig, D.A. Rotsch, L.L. Radford, E.M. Weis, A.B. Taylor, C.L. Barnes, S.S. Jurisson
p624
Technetium-99m Schiff base complexes, more commonly known as the “Q-series”, have been considered for use
as single photon emission computed tomography (SPECT) imaging agents. Rhenium is often a structural analogue
to technetium and has isotopes ideal for radiotherapy and imaging, therefore Re- and Tc-Schiff base chemistry has
been investigated.
99m 123/131
Synthesis of Tc analogue of I-mIBG for possible use in neuroendocrine tumor
imaging
Navin Sakhare, Soumen Das, Anupam Mathur, V.V. Murhekar, R. Krishna Mohan, G. Prabhakar, S.S.
Sachdev
p624–625
123 131
Introduction: Radio-iodine ( I/ I) labeled meta-iodobenzylguanidine (mIBG) is a popular radiopharmaceutical
used worldwide for diagnosis of neuroendocrine tumors, particularly adrenal medullae related tumors. However,
123 131
X
X
X
X

123 131
limited availability of I and non-ideal diagnostic nuclear characteristics of I necessitate the need for a rationale
substitute. 99m
Tc has been the clinical choice due to its ideal nuclear characteristics and easy availability. Hence, an
attempt has been made to synthesize a 99m
Tc analogue of mIBG using '4 + 1' labeling approach and subsequently
evaluating its efficacy for the aforementioned application.
III
Tc -based mixed complexes for the design and the development of new SPECT tracers
N. Salvarese, N. Morellato, A. Dolmella, L. Meléndez-Alafort, D. Carpanese, A. Rosato, F. Refosco,
C. Bolzati
p625
The trivalent state is the most stable oxidation state of technetium and rhenium, however, none of the
radiopharmaceuticals currently in clinical use contains the metal in this oxidation state. We present here a general
procedure for the preparation of a series of six-coordinated mixed ligand [ 99/99m Tc III
(PS) (L n
2
)] compounds, (PS =
phosphino-thiolate; L n = dithiocarbamate) to design a new class of Tc III
-imaging agents.
99m
Biodistribution of 80 nm iron oxide nanoparticles labeled with Tc in Balb/c mice
Saeed Shanehsazzadeh, Afsaneh Lahooti
p625
Introduction: Recently ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs) have been widely
used for medical applications. One of their important applications is using these particles as MRI contrast agent.
The aim of this study was to evaluate the biodistribution of dextran coated iron oxide NPs labeled with 99m
Tc with
80 nm hydrodynamic size via intravenous injection in Balb/c mice.
99m 3 +
(2-Hydroxyphenyl)diphenylphosphine as fac-[Re/ Tc(CO) ] -ligand
A. Shegani, C. Triantis, F. Tisato, V. Peruzzo, B. Nock, T. Maina, C. Raptopoulou, V. Psycharis, I.
Pirmettis, M. Papadopoulos
p625–626
1 2
2
Mixed ligand fac-[ML L (CO) 3
] (M = Tc(I), Re(I)) complexes, containing a monoanionic bidentate L and a
monodentate ligand L 1
, are particularly interesting for the development of new radiopharmaceuticals. Coupling of a
vector to one ligand and tuning of pharmacokinetics with the other provide unique design versatility. In this work we
have studied (2-hydroxyphenyl)diphenylphosphine (POH) as a ligand to the fac-[Re/ 99m
Tc(CO) 3
] +
-fragment. In
equimolar amounts, POH readily reacts with the [NEt 4 ] 2 [ReBr 3 (CO) 3 ] precursor to afford fac-[Re(PO)(H 2 O)(CO) 3
],
1.
99m 3 +
Neutral fac-[Re(I)/ Tc(I)(CO) ] -complexes with the new PO/L-donor system
A. Shegani, C. Triantis, F. Tisato, V. Peruzzo, B. Nock, T. Maina, C. Raptopoulou, V. Psycharis, I.
X
X
X

p626
We have recently investigated potential means toward neutral mixed-ligand fac-[ML 1 L 2
(CO) 3
] (M = Tc(I), Re(I))
complexes, containing the (2-hydroxyphenyl)-diphenylphosphine (PO − ) ligand (L 2
). For such purposes, the fac-
[Re/ 99m
Tc(PO)(H 2 O)(CO) 3
] precursor (1) has been synthesized after reaction of equimolar amounts of POH with
[NEt 4 ] 2 [ReBr 3 (CO) 3 ]. In this work, we have further investigated the substitution of labile H 2
O-molecule in 1 by a
monodentate ligand L 1
, such as imidazole (im), isocyanide (isc) and pyridine (py).
3 99m
Mixed pharmacophore fac-[M(OO)(isc)(CO) ] (M = Re, Tc) complexes
Charalampos Triantis, Marina Sagnou, Barbara Mavroidi, Maria Paravatou-Petsotas, Ioannis
Pirmettis, Minas Papadopoulos, Maria Pelecanou
p626
99m
Tricarbonyl fac-[M(OO)(isc)(CO) 3
] (M = Re, Tc) complexes with the β-diketones acetylacetone or curcumin as
the OO bidentate ligands and cyclohexyl isocyanide as the monodentate ligand give stable neutral complexes [1].
Herein, two new fac-[Re(OO)(isc)(CO) 3
] complexes of acetylacetone and curcumin are presented with the N-(4-
benzothiazol-2-yl-phenyl)-3-isocyano-propionamide as the isc monodentate ligand. In these complexes the 2-(4′-
aminophenyl)benzothiazole pharmacophore, known for its anticancer as well as β-amyloid binding properties, is
introduced adequately distanced from the tricarbonyl core to allow for interaction with putative binding sites or
tissues.
99m 2
New cis-[Re/ Tc(NO)(P)(isc)(CO) ] mixed ligand complexes
C. Triantis, A. Shegani, C. Raptopoulou, V. Psycharis, M. Pelecanou, I. Pirmettis, M. Papadopoulos
p626
99m
The synthesis and characterization of new dicarbonyl cis-[Re/ Tc(NO)(P)(isc)(CO) 2
] complexes, where the
bidentate ligand is quinaldic acid (NO) and the monodentate ligands are triphenylphosphine (P) and cyclohexyl
isocyanide (isc), are described. Reaction of the [NEt 4 ] 2 [ReBr 3 (CO) 3
] precursor with quinaldic acid results in the
formation of the aqua complex fac-[Re(NO)(H 2 O)(CO) 3
], 1, which reacts readily at room temperature with equimolar
quantity of cyclohexyl isocyanide to produce the mixed “2 + 1” ligand complex fac-[Re(NO)(isc)(CO) ], 2.
3
New trans-cis-[Re(NO)(isc) 2 (CO) 2 ] and [Re(NO)(isc) 3
(CO)] mixed ligand complexes
C. Triantis, A. Shegani, C. Raptopoulou, V. Psycharis, M. Pelecanou, I. Pirmettis, M. Papadopoulos
p626–627
+
Our interest in new mixed ligand systems for the tricarbonyl fac-[Re(CO) 3
] core has led us to investigate the
quinaldic acid/isocyanide combination. We present herein the synthesis and characterization of the mixed ligand
X
X
X
X

complexes fac-[Re(NO)(isc)(CO) 3 ], trans-cis-[Re(NO)(isc) 2 (CO) 2 ], and [Re(NO)(isc) 3
(CO)], where NO is the
bidentate ligand quinaldic acid and isc is the monodentate ligand cyclohexyl isocyanide. Reaction of the
[NEt 4 ] 2 [ReBr 3 (CO) 3 ] precursor with quinaldic acid results in the formation of the aqua complex fac-[Re(NO)(H 2
O)
(CO) 3
] which reacts readily at room temperature with equimolar quantity of cyclohexyl isocyanide to produce the “2
+ 1” mixed ligand complex fac-[Re(NO)(isc)(CO) ].
3
99m 2 3
Phosphite, phosphine, and arsine as ligands for fac-[Re/ Tc(quin)(H O)(CO) ]
C. Triantis, A. Lazopoulos, A. Panagiotopoulou, C. Raptopoulou, V. Phycharis, M. Pelecanou, I.
p627
99m
+ 99m
In order to investigate new mixed ligand systems for the fac-[Re/ Tc(CO) 3
] core, the fac-[Re/ Tc(quin)(H 2
O)
(CO) 3
] precursor – containing the NO bidentate quinaldic acid (quinH) – was synthesized and reacted with
phosphites, phosphines and arsines as monodentate L ligands. Specifically, in this work, we present the synthesis
and characterization of the new fac-[Re(quin)(L)(CO) 3
] complexes where L is trimethylphosphite,
tris(hydroxymethyl)phosphine, or triphenylarsine. Reaction of the precursor fac-[Re(quin)(H 2 O)(CO) 3
], 1, with the
each of the L ligands in methanol resulted in the formation of the corresponding mixed ligand complex fac-[Re(quin)
(L)(CO) ], 2–4 in high yield.
3
A new kind of imaging agent for myocardial fatty acids metabolism
Tian Xue, Xiang Li, Jianping Liu, Huabei Zhang
p627
Thiophene group was introduced at the ω-position of the long fatty acids with an expectation to increasing the
retention time and uptake in the heart and reducing the blood bottom. 99m Tc-CpTODTPM, 99m
Tc-CpTODTBM,
99m 99m
Tc-CpTOHTPM, Tc-CpTOHTBM and their references CpTReODTPM, CpTReODTBM, CpTReOHTPM,
CpTReOHTBM were designed and synthesized respectively through a traditional method–double ligand transfer
reaction. The radiolabeling yields of these compounds were from 10% to 15%. The stability for these compounds
was very good, they existed in their original form when they are put in SD rat serum for 3 h at 37 °C and NS at room
temperature for 3 h.
Introduction of a hydrocarbon beta-ala linker reduced the renal uptake of Tc-99m-labeled Arg-
Ala-Asp-conjugated alpha-MSH peptide
Jianquan Yang, Yubin Miao
p627
It is highly desirable to reduce the high renal uptake of 99m Tc-RAD-Lys-(Arg 11
)CCMSH (92.97 ± 21.72% ID/g at 2 h
post-injection) which we reported previously. The purpose of this study was to examine whether the replacement of
the Lys linker with a βAla linker could decrease the renal uptake of 99m Tc-RAD-βAla-(Arg 11
)CCMSH. Methods: The
3,4,10 7 11 11
X
X
X

3,4,10 7 11
11
RAD motif {cyclic(Arg-Ala-Asp-DTyr-Asp)} was coupled to [Cys , D-Phe , Arg ]α-MSH 3–13
{(Arg )CCMSH} via
a βAla linker to generate the novel RAD-βAla-(Arg 11
)CCMSH peptide.
99m
Synthesis and preclinical evaluation of novel Pteroy-lys derivatives labeled with Tc for FR-positive
tumor imaging
Qian Yu, Yuan Chen, Chun Zhang, Yingfang He, Jie Lu
p627–628
99m
Introduction: The purpose of this study was to develop novel Tc-labeled folate receptor targeting tumor imaging
agents with optimal characteristics.Methods: Two novel HYNIC-conjugated Pteroyl-lys derivatives with hydrophilic
linkers, HYNIC-penta-lys-Pteroyl, 1, and HYNIC-GlyGly-lys-Pteroyl, 2, were designed, synthesized and radiolabeled
with 99m Tc using Tricine/TPPTS as coligands. Biological evaluations of the two 99m
Tc-labeled complexes were
performed with FR-positive KB cell lines and athymic nude mice bearing KB tumors.
Single-domain antibodies: Next-generation targeting vectors for molecular imaging
Kristof Zarschler, Katja Zscheppang, Franz Kapplusch, Nils Cordes, Holger Stephan
p628
Single-domain antibodies (sdAbs) provide significant benefits over conventional antibodies and fragments thereof in
terms of size, stability, solubility as well as tumour uptake and blood clearance. Thus, sdAbs have been identified
as valuable next-generation targeting moieties for molecular imaging and drug delivery in the past years. Since
these probes are much less complex than conventional antibody fragments, bacterial expression represents a facile
method for production of sdAbs in large amounts as soluble and functional proteins.
99m
A possible mechanism for trapping Tc-HL91 in hypoxic tumor
Lin Zhu, Wenbo Fan, Yan Zhang, Jinping Qiao
p628
99m
Introduction: Selective trapping mechanism for Tc-HL91, a hypoxia imaging agent, is still not well-defined.
Previously, Brauers et al. [Eur J Nucl Med, 24 (1997), p. 943] proposed that 99m
Tc-HL91 can adopt either TcO-BnAO
or TcO -BnAO form in solution. We hypothesize that interconversion between these two forms may be
2
99m
important for hypoxic cell uptake of Tc-HL91 [Theor Chem Acc 2008;121: 271–278]. We test this hypothesis by
HPLC under different conditions in solution.
99m
The preparation and preclinical evaluation of Tc-labeled microbubbles for bimodal
ultrasound and SPECT imaging
Aimen Zlitni, Afaf R. Genady, Nancy Janzen, John F. Valliant
p628
X
X
X

Because of its low cost and portability, ultrasound (US) imaging is seeing rapid growth compared to other
modalities. The ability to link targeting ligands to the surface of US contrast agents, which include microbubbles
(MBs), has further expanded the utility of US imaging to include molecular imaging applications. Quantitative
evaluation of new targeted ultrasound agents however remains a major challenge. The aim of the work to be
presented is the development of a convenient and versatile platform for the preparation and purification of targeted
and technetium labeled MBs.
89
3,4,3-(LI-1,2-HOPO): An alternative chelator for Zr radiopharmaceuticals
Melissa A. Deri, Shashikanth Ponnala, Brian M. Zeglis, Gabor Pohl, Joseph J. Dannenberg, Jason S.
Lewis, Lynn C. Francesconi
p629
89
Zr is an attractive radionuclide for antibody-based PET tracers because its 78.41 h half-life matches the biological
residence time of IgG antibodies. Currently, antibodies are radiolabeled with 89
Zr using desferrioxamine B (DFO);
however, the observed uptake of radioactivity in the bones of mice given 89
Zr-DFO-antibody constructs suggests in
vivo release of 89 Zr 4+ [1]. A better chelator for 89 Zr 4+ could eliminate the release of the bone-seeking 89 Zr 4+
cation in
vivo and produce a safer PET tracer.
A novel multivalent bifunctional siderophore chelator scaffold for radiolabeling with gallium-68
based on fusarinine C
Chuangyan Zhai, Peter Knetsch, Christine Rangger, Dominik Summer, Michael Blatzer, Hubertus
Haas, Elisabeth von Guggenberg, Roland Haubner, Clemens Decristoforo
p629
The cyclic peptide siderophore triacetylfusarinine C (TAFC) showed excellent complexing properties for 68
Ga
resulting in high specific activity and excellent metabolic stability. We postulated that, starting from its deacetylated
form fusarinine C (FSC) trimeric bioconjugates are directly accessible to develop novel 68
Ga-labeled targeted
radiopharmaceuticals. For a proof of principle, the ferric form of FSC was coupled with an α v β 3
integrin targeting
RGD sequence via in situ activation using HATU/HOAt and DIPEA.
Synthesis of tridentate ligand: Potential theranostic application of a radioarsenic trithiol
complex
Anthony J. DeGraffenreid, Cathy S. Cutler, Charles Barnes, Silvia S. Jurisson
p629
Arsenic-72 is a 26 h half-life positron emitter (2.49 MeV) with nuclear properties useful for diagnostic imaging by
positron emission tomography (PET). Arsenic-77 is a 38.8 h half-life beta emitter (683 keV) potentially useful for
X
X
X
X

radiotherapy applications. Radioisotopes of arsenic have half-lives suitable for use with antibodies as targeting
vectors while traditional radionuclides, 11 C, 18 F, 64 Cu, and 86
Y, do not have sufficiently long half-lives (up to 4 days)
to permit chemical derivatization and in vivo localization for radioimaging or radiotherapy.
64 v 3
Robust and efficient bifunctional chelators for Cu to target α β integrin
Nisarg Soni, Nikunj Bhatt, Gwang Il An, Jeongsoo Yoo
p629–630
64
The choice of bifunctional chelator (BFC) and radioisotope is crucial for imaging of biological function. Cu (t 1/2
=
12.7 h) is a β + and β −
emitter, making it useful for both imaging and radiotherapy. The accuracy of imaging with
64
Cu often depends on BFC and hence, the importance of BFC cannot be overemphasized in terms of Cu–BFC
complex robustness in vivo.
Development of a PSMA targeting nanoparticle as PET/MR multimodal imaging probe
Sung-Hyun Moon, Bo Yeun Yang, Yun-Sang Lee, Dong Soo Lee, June-Key Chung, Jae Min Jeong
p630
Development of PET/MR multimodal probes for PET/MR scanners is important. Iron oxide nanoparticles are
adequate MR imaging probes. For PET/MR multimodal imaging, chelator introduction is necessary for radiometal
labeling. Additionally, specific ligands and PEG chains also should be introduced for active targeting. However,
introduction of multiple ligands on to a nanoparticle is very difficult. Recently, we published a straightforward
method for multifunctional nanoparticle preparation by encapsulation with specific amphiphiles [1].
Tumor pretargeting with Diels–Alder: A TCO derivative with improved properties
Raffaella Rossin, Sander M.J. van Duijnhoven, Sandra M. van den Bosch, Marc S. Robillard
p630
The reaction between mAb-trans-cyclooctene (TCO) and radiolabeled tetrazines via the Diels–Alder reaction has
potential for pretargeted tumor imaging and radiotherapy [1]. Here we present the in vivo evaluation of an
oxymethylacetamide-TCO (TCOac), which is highly reactive towards tetrazines (k 4 −1 −1
2
= 13.5 ± 0.1 × 10 M s ) and
less hydrophobic than the TCO used previously [1,2]. In tumor-free mice, CC49-TCOac circulates longer (T 1/2
=
22.0 h) than our previous CC49-TCO (T = 14.1 h) [1] most likely due to the lower hydrophobicity of TCOac.
1/2
Metal-chelating polymers developed for mass cytometry as a potential route to high activity
radioimmunotherapeutic agents
Daniel Majonis, Xudong Lou, Olga Ornatsky, Isaac Herrera, Mark Nitz, Mitchell A. Winnik, Dmitry
Bandura, Vladimir Baranov, Scott D. Tanner
p630
X
X
X

We have developed metal-chelating polymers to enable the technology of mass cytometry. Briefly, mass cytometry
is a bioanalytical technique for single-cell protein analysis. Antibodies are tagged by the covalent attachment of a
metal-chelating polymer (MCP) carrying multiple ions of one stable lanthanide isotope, after which a cocktail of
different antibodies is used to stain a sample of cells. The cells are individually introduced into an inductively
coupled plasma mass spectrometer (ICP-MS), and the lanthanide signal relates back to the antigen profile of each
cell.
44m 44
Promising prospects of Sc/ Sc as an in vivo generator: Biological evaluation and PET
images
S. Huclier-Markai, C. Alliot, J. Rousseau, N. Chouin, M. Fani, P. Bouziotis, T. Maina, C.S. Cutler, J.
Barbet
p631
44 +
47 −
68
Sc (β , T 1/2
= 3.97 h) for diagnostics/ Sc (β ,γ, T 1/2
= 3.351 d) for therapy is a valuable alternative to Ga or
64 Cu for PET-imaging of cancer prior to 177 Lu- or 90 Y-based radionuclide therapy. 44 Sc has an isomeric state, 44m
Sc
(T 1/2
= 58.6 h), co-produced with 44 Sc that can be used as an in vivo 44m Sc/ 44 Sc generator. When 68 Ga or 111
In is
used for pre-therapeutic imaging, for therapeutic radionuclides such as 90 Y or 177
Lu, different in vivo uptake
especially in critical organs such as bone and liver is observed due to dissimilar coordination chemistry, thus not
truly reflecting the pharmacokinetics of the therapeutic agent.
Gallium(III) complexes with new acyclic chelators for radiopharmaceutical design
Francisco Silva, M. Paula, C. Campello, Lurdes Gano, Célia Fernandes, Isabel C. Santos, Isabel
Santos, Jose R. Ascenso, M. João Ferreira, António Paulo
p631
67/68
Ga-radiopharmaceuticals design is a topic of utmost importance in radiopharmaceutical chemistry, due to the
68 68 68
on growing impact of Ga in the design of PET probes as a result of the recent availability of GMP Ge/ Ga
generators [1]. In this context, we have studied cold and/or radioactive Ga complexes with new N 4 O 2
-donor Schiff
base ligands (H 2 L 1 , H 2 L 3 ) and corresponding amine derivatives, (H 2 L 2 , H 2 L 4
). Ligands were obtained based on the
diethylenediamine backbone and by introducing pyrazolyl and pyridyl arms at the central nitrogen atom.
Nanoparticle bioconjugates labeled with alpha emitters
E. Leszczuk, L. Janiszewska, P. Koźmiński, A. Morgenstern, F. Bruchertseifer, A. Bilewicz
p631
Alpha particle emitting isotopes are in considerable interest for radionuclide therapy because of their high
cytotoxicity and short path length. In our studies we investigated the use of TiO nanoparticles as 2 potential carriers
225 213 211
X
X
X
X

225 213 211
for Ac/ Bi and gold sulphide core shell nanoparticles as vehicle for At. In our experiments we tested two
different methods of labelling. The first one was based on the possibility of forming strong bonds with radionuclides
on the surface of the nanoparticles. In the second one, TiO 2 nanoparticles and Au 2
S/Au core shell nanoparticles
were doped with 225 Ac and 211
At during the process of synthesis.
Evaluation of metallofullerens for potential use in therapy
Tamer Sakr, Harry C. Dorn, Zianyuan Zhang, Cathy S. Cutler
p631–632
Therapy requires delivering toxic doses selectively to the diseased or cancer cells while sparing all normal tissues.
Conventional agents have resulted in low therapeutic indices due to suboptimal biodistribution where only a minute
portion of the intravenously administered drug reaches the target but large doses are delivered to normal tissues.
Nanoparticles are being developed as an alternative due to their size and ability to circumvent some of the hurdles
encountered with traditional agents.
Acyclic chelating ligands for PET imaging of tumor hypoxia with Ga-68
Caterina F. Ramogida, Cara L. Ferreira, Jacqueline F. Cawthray, Chris Orvig, Michael J. Adam
p632
Recently, our group has developed the linear N 3+
4 O 2 chelating ligand, H 2
dedpa that binds Ga quickly and under
mild conditions whilst exhibiting exceptional kinetic inertness in vitro – ideal properties to be incorporated into a
Ga PET imaging agent [1]. Herein, we report nitroimidazole (NI) derivatives of H 2
dedpa to investigate specific
targeting of hypoxic tumor cells, given that NI can be reduced and retained exclusively in hypoxic cells [2]. Nine N-alkylated-
NI derivatives of H dedpa and H CHXdedpa (derivative with a chiral backbone) have been synthesized
68
2 2
and screened for their ability to bind gallium.
45
Preparation of [ Ti] Ti-salan-dipic
Gregory W. Severin, Andreas I. Jensen, Jesper Fonslet, Fedor Zhuravlev
p632
45
We report the carrier-free radiochemical synthesis of a neutral, bio-active, titanium-45 complex, [ Ti]Ti-salan-dipic.
In 2012, the Huhn group at Universität Konstanz reported the non-radioactive compound, Ti-salan-dipic, and
demonstrated therapeutic efficacy in a xenograft cervical cancer mouse model as well as enhanced in-vitro
cytotoxicity over several other titanium-based chemotherapeutics [1]. The mechanism of action for this class of
therapeutics is under investigation and the determination of which will be aided by radiotracing and PET with 45
Ti.
Development of Ga-PpIX peptides as fluorescence/PET imaging probes
Neha Sharma, Babak Behnam Azad, Leonard G. Luyt
X
X
X

p632
The use of gallium-68 for non-invasive PET imaging has gained much interest with the increasing availability of
68 Ge/ 68
Ga generators. Protoporphyrin IX (PpIX) was utilized for gallium coordination owing to its inherent
fluorescence characteristics and suitable cavity size, allowing for fluorescence microscopy and PET imaging studies
with a single structural manifold. PpIX was placed at the N-terminus of integrin targeting tripeptide RGD, through a
short PEG linker [1]. Coordination with 69/71
Ga provided a fluorescent analogue that exhibited significant uptake in
the melanoma cell line MDA-MB-435, as indicated by fluorescence microscopy.
Bispidines as a platform for targeted multimodal imaging
Peter Comba, Sebastian Hunoldt, Michael Morgen, Jens Pietzsch, Jörg Steinbach, Holger Stephan,
Martin Walther
p632–633
Ligands based on 3,7-diazabicyclo[3.3.1]nonane (bispidine) form very stable coordination compounds, in particular
with first row transition metal ions. Considering multiple functionalization, bispidines are promising candidates for
pharmaceutical targeting and multimodal imaging. Due to the formation of thermodynamically stable and kinetically
inert Cu II complexes, penta- and hexadentate bispidine ligands are well suited for 64
Cu positron emission
tomography imaging and radiotherapy ( 64 Cu/ 67
Cu).
64
[ Cu]Cu-CryptTM – A novel cryptate for copper-64?
Christian Foerster, James C. Knight, Melinda Wuest, Brendan Rowan, Suzanne E. Lapi, Angelo J.
Amoroso, Peter G. Edwards, Frank Wuest
p633
Objective: Radiopharmaceutical evaluation of novel cryptand CryptTM for labeling with 64Cu.
2 2 64
DOTHA and NOTHA —New chelates for highly efficient Cu radiolabeling
S. Ait-Mohand, C. Denis, G. Tremblay, M. Paquette, B. Guérin
p633
64
With the goal of identifying improved bifunctional chelates (BFCs) that stably complex with fast kinetics Cu, we
have synthesized DOTHA 2 and NOTHA 2
, two BFCs derived from polyazacycles and bearing methyl-hydroxamic
acid pendant arms. Radiolabeling experiments were performed varying the pH and the counterion, and each
chelate has been compared to currently used BFCs DOTA and NOTA with respect to radiolabeling efficiency and
stability. DOTHA 2 and NOTHA 2
were prepared with great yields and ease of synthesis in solution and on solid
phase.
X
X
X
X

Kinetic inertness evaluation of copper complexes using gel electrophoresis techniques
Manja Kubeil, Kristof Zarschler, Jörg Steinbach, Holger Stephan
p633–634
The development of highly stable radiocopper complexes is one major challenge that seeks to further improve
radiopharmaceuticals for medicinal applications. In many cases, radiocopper complexes suffer the fate of
dissociation in vivo which is contributed to loss of the radionuclide resulting amongst others in an unspecific
accumulation in non-target tissues and thus in poor target-to-background ratios. The kinetic lability has been
addressed as major issue for transchelation or dissociation in vivo.
141
Ce-DOTMP: A theranostic agent for metastatic bone tumor
K.V. Vimalnath, A. Rajeswari, H.D. Sarma, Sudipta Chakraborty
p634
141
141
Owing to its suitable decay properties, Ce [T ½
= 32.5 d to Pr (stable), E β(max)
= 434 keV (70%), 580 keV
(30%), E γ
= 145 keV (48.5%)] could be envisaged as a promising radionuclide for developing theranostic agents for
metastatic bone tumor. Cerium-141 was produced via 140 Ce(n,γ) 141
Ce route with a specific activity of 200 ± 18
MBq/mg by irradiation of natural Ce(NO 3 ) 4
target (88.45% 140 Ce) at a thermal neutron flux of 1 × 10 14 n/cm 2
/s for
60 d. Cerium-139 and 143
Pr are the radionuclidic impurities co-produced, which could be avoided by the use of
isotopically enriched 140
Ce target.
DFO* – A novel octadentate BFCA for zirconium-89
Malay Patra, Andreas Bauman, Christiane Fischer, Cristiane Mari, Gilles Gasser, Thomas Mindt
p634
Zirconium-89 ( 89
Zr) is an emerging new metallic radionuclide with promising characteristics for PET, in particular for
immuno-PET. A major limitation of the use of 89
Zr in nuclear medicine is the lack of appropriate methods for the
stable chelation of the radiometal. To date, 89
Zr-based imaging probes are obtained exclusively through derivatives
of desferrioxamine (DFO), a chelator which does not complete the octadentate coordination sphere of the
radiometal. There is compelling evidence that incomplete coordination of 89
Zr by DFO is responsible for the
observed instability of the chelate in vivo.
64
Cu-dithiocarbamate compounds for theragnostic applications: Preliminary in-vitro studies
N. Morellato, G. Cicoria, V. Gandin, N. Salvarese, C. Marzano, C. Malizia, C. Bolzati
p634
64
X
X
X

64
In vitro evaluation of Cu-labeled GE11-conjugates
F. Oertel, F. Starke, W. Sihver, J. Steinbach, H.J. Pietzsch
p634–635
The epidermal growth factor receptor (EGFR) is frequently overexpressed in epithelial tumors and consequently
represents an important target for cancer diagnosis and therapy. Recently, a novel peptide sequence (GE11,
YHWYGYTPQNVI) was identified to bind the EGFR with high affinity in vitro (K d
= 22 nM) as well as in vivo [1].
These promising data suggest that a GE11-conjugate, which is radiolabeled with a positron-emitting radionuclide,
may be used for the assessment of EGFR-levels of tumors and metastases by positron emission tomography, thus,
identifying patients which can be medicated by anti-EGFR therapy.
nat/67/68
Structural investigation of Ga HBED-CC complexes
Karl Ploessl, Zhihao Zha, Seok Rye Choi, Lin Zhu, Hank Kung
p635
68
Introduction: With the availability of Ge/Ga generators, Ga is becoming an isotope of choice for developing PET
agents without a cyclotron. Cyclic chelators such as DOTA, NOTA or acyclic chelators, such as N,N′-bis[2-hydroxy-
5-(carboxyethyl)benzyl] ethylenediamine-N,N′-diacetic acid (HBED-CC), are often used to generate functional
chelating ligands for binding Ga to bioactive organic molecules primarily because they can complex [ 68 Ga]Ga 3+
in
solution at a much faster rate than other ligands. It is expected that Ga 3+
HBED-CC may form structural isomers
(enantiomers and stereo-isomers).
H 4 octapa vs H 4
C3octapa: The difference of a single carbon atom
Eric W. Price, Brian M. Zeglis, Jacqueline F. Cawthray, Jason S. Lewis, Michael J. Adam, Chris Orvig
p635
The ligands H 4 C3octapa and p-SCN-Bn-H 4
C3octapa were synthesized for the first time. These new ligands were
compared with the previously published ligands H 4 octapa and p-SCN-Bn-H 4
octapa, to determine whether addition
of a single carbon atom to the backbone of these ligand scaffolds would effect metal/radiometal chelation and
stability. The In 3+ and Lu 3+
complexes of H 4
C3octapa were synthesized, studied by NMR spectroscopy, DFT
structure analysis, potentiometric titrations, and compared to the analogous H octapa complexes.
4
Binding properties of radiolabeled cetuximab conjugates
W. Sihver, M. Schubert, H. Stephan, B. Graham, L. Spiccia, M. Baumann, J. Pietzsch, J. Steinbach,
H.J. Pietzsch
p635
The monoclonal antibody cetuximab (C225) binds with high affinity to the epidermal growth factor receptor (EGFR),
X
X
X
X

which is a major molecular target for treatment of different types of cancer. Radiolabeled C225 has been proven to
be appropriate for cancer imaging and treatment. This study comprises an affinity comparison of different C225
conjugates incorporating p-SCN-Bn-NOTA (1), p-SCN-Bn-dipicolyl-TACN (2) and p-SCN-Bn-CHX-A″-DTPA (3).
Evaluation of the K i
values using homogenates of A431 cells (EGFR high /Her2 high
expression) revealed minimal loss
of affinity for these conjugates compared to unchanged C225.
64
PCB-TE2A-NCS: A cross bridged BFC for Cu-based radiopharmaceuticals
Nisarg Soni, Nikunj Bhatt, Gwang Il An, Jeongsoo Yoo
p636
64
Bifunctional chelator (BFC) is a key component in developing Cu-based imaging agents. For the successful
development of 64
Cu-based imaging agents, the BFC is required to make facile and strong conjugation with
biomolecule as well as to hold radiometal ions firmly in physiological conditions.
Peptide conjugates for EGFR-targeting
K. Viehweger, J. Hesse, H. Stephan, L. Spiccia, B. Graham
p636
We have synthesized 64
Cu-labelled peptide conjugates based on a 1,4,7-triazacyclononane (TACN) framework that
may be applied for in vivo PET imaging. A peptide sequence (LARLLT, “D4”) was used to target the epidermal
growth factor receptor (EGFR). Overexpression and mutations of this cell-surface receptor are involved in
carcinogenesis and progression of many human cancers.
64
Polyacrylamide nanogel systems with Cu chelating cross-linkers for PET imaging
Alexander G. White, Jacques Lux, Minnie Chan, Carolyn J. Anderson, Adah Almutairi
p636
In recent years, increasing attention has been given to nanotechnologies within the fields of molecular imaging
combined with drug delivery. We recently reported the design and synthesis of metal-chelating crosslinkers
enabling formulation of polyacrylamide hydrogels (nanogels) for magnetic resonance imaging (MRI); however, a
major drawback of this imaging modality is lack of sensitivity. To overcome this limitation, nanogels were formulated
containing DTPA, DOTA, and NOTA metal chelators for Cu-based PET imaging64 .
The site-specific radiometallation of antibodies on the heavy chain glycans
Brian M. Zeglis, Charles B. Davis, Robert Aggeler, Brian J. Agnew, Jason S. Lewis
p636
X
X
X
X

Immunoconjugates labeled with radiometals have emerged as critical tools in nuclear medicine. However, the lack
of site-specificity in traditional methods for the attachment of chelators can lead to poorly-defined constructs and
impair immunoreactivity. To circumvent these issues, we have developed a chemoenzymatic system for the site-specific
radiolabeling of antibodies on the heavy chains. The methodology consists of four steps: (1) the removal of
terminal galactose residues on the antibody heavy chain using β-1,4-galactosidase; (2) the incorporation of azide-modified
galactosamine residues using a substrate-promiscuous galactosyltransferase; (3) the strain-promoted click
conjugation of chelator-modified dibenzocycloctynes to the azide-modified sugars; and (4) the radiolabeling of the
resulting antibody construct.
Quality control of research and GMP grade radiometals: Example Lu-177
C.S. Cutler
p637
An important aspect of manufacturing high quality radionuclides and radiopharmaceuticals for medical applications
is establishing appropriate quality control standards and testing. USP monographs exist and are being updated,
which include specifications for radionuclide identification and assay. Additionally specifications and testing must be
established based on the criteria of the end user. Important specifications include specific activity, radionuclidic
purity, radiochemical purity, pH, chemical impurities as well as pyrogenicity and sterility to name a few.
68
Ga-Dotatate radiochemical purity impacts patient image quality: 90% is not enough
M. Bauwens, I. Pooters, H. Eram, F.M. Mottaghy, M. van Kroonenburgh
p637
68
Ga-Dotatate has been extensively used in the last decade as a tool to diagnose neuroendocrine tumors. There is
currently no European monograph available, but there are multiple radiosynthesis methods described in literature,
as well as multiple quality control methods. In the past year, it has been reported that radiolysis plays a significant
role in radiochemical purity, which can be as low as 76%.
Select All View Abstracts | Export Citations | Email a Colleague | Add to Reading List
< Prev 1 2 3 Next >
X
X
Copyright © 2014 Elsevier Inc. All rights reserved. | Privacy Policy | Terms & Conditions | About Us | Help & Contact
The content on this site is intended for health professionals.
Advertisements on this site do not constitute a guarantee or endorsement by the journal, Association, or publisher of the quality or value of such product or of the claims made for it by its
manufacturer.

RSS Feeds Mobile
Welcome, Konstantin German
Claim Subscription | Subscribe | My Account | Logout
Articles & Issues For Authors Journal Info SRS Subscribe More Periodicals
All Content Search Advanced Search
Volume 41, Issue 7, p545-650
< Previous Next >
August 2014
Alert me when new issues and articles are available via Email Alert or RSS Feed .
< Prev 1 2 3
Select All
Search within this issue
View Abstracts | Export Citations | Email a Colleague | Add to Reading List
Browse By Issue
2010 - present
Vol. 41
Issue 7, August 2014, p545-650
List of Issues
Go
Enlarge Cover
111
Phosphoramidon enhances tumor uptake of truncated [ In-DOTA]gastrins
A. Kaloudi, E. Lymperis, E.P. Krenning, B.A. Nock, M. de Jong, T. Maina
p637
Radiolabeled gastrin analogs have become attractive candidates for diagnosis and therapy of CCK2R-positive
cancer. We present three new analogs of [DOTA]MG11 ([(DOTA)DGlu 10
]gastrin(10–17)), whereby the oxidation-susceptible
15 15 15 15
Met is substituted by: Ahp (SG3), Nle (SG4) or Leu (SG5). Most importantly, we report on
significant effects induced by in vivo inhibition of neutral endopeptidase (NEP). For this purpose, the potent NEP-inhibitor
111
phosphoramidon (PA) was coinjected with the respective In-radioligands in mice.
X

Pharmacological characterization of α-MSH-derivatives
W. Sihver, F. Gao, C. Jurischka, C. Haase-Kohn, J. Steinbach, D. Carta, C. Bolzati, A. Calderan, J.
Pietzsch, H.J. Pietzsch
p637–638
The melanocortin-1 receptor is known to be overexpressed in melanoma. Thus, it is a potential target for novel α-
MSH peptide derivatives aiming at diagnosis and therapy of melanoma. In this study, NOTA-NCS was conjugated
with two peptides: NAP-NS1, a linear peptide with 9 amino acids (Ahx-βAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH 2
)
and NAP-NS2, a lactam bridge-cyclized peptide with 12 amino acids (ε-Ahx-β-Ala-cyclo(Lys-Glu-His-D-Phe-Arg-
Trp-Glu)-Arg-Pro-Val-NH ) each with the sequence His-Phe-Arg-Trp for biological activity.
2
68
Evaluation of [ Ga]-DOTA ghrelin (1–19) in LNCaP prostate carcinoma
Carlie L. Charlton, Savita Dhanvantari, Leonard G. Luyt
p638
Ghrelin is a 28-amino acid peptide that is the endogenous ligand for the growth hormone secretagogue receptor-1a
(GHSR-1a). GHSR-1a is highly expressed in prostate cancer and previous work has demonstrated that ghrelin
distinguishes between healthy, benign and cancerous prostate tissue ex vivo. We have developed a DOTA ghrelin
(1–19) analogue capable of targeting the GHSR-1a. Using orthogonal protecting groups, diaminopropanoic acid-3
and lysine-19 allowed for functionalization of the peptide with octanoic acid and DOTA respectively.
64 2
CuCl : New theranostic agent
G. Valentini, P. Panichelli, C. Villano, G. Pigotti, D. Martini
p638
64
CuCl 2
has a high tumor uptake [1]. This uptake is due to an overexpression in tumor cells of the copper
transporter CTR1 [2] and probably for the increase of DNA activity replication. Our aim is to evaluate the potential of
64
CuCl 2
as theranostic agent in two different lines of tumors: prostate cancer and uterine cancer. For this reason we
examined two different patients in metastatic phase using case report method. These patients presented diagnosis
of metastatic lesions studied with FDG PET/CT scan and CT scan.
47
Preclinical application of Sc-folate – A pilot study in tumor-bearing mice
Cristina Müller, Maruta Bunka, Stephanie Haller, Ulli Köster, Nicholas van der Meulen, Andreas
Türler, Roger Schibli
p638
47
− −
Purpose: The aim of this study was to investigate the use of Sc (T 1/2
= 3.35 d) for β -radionuclide therapy (Eβ
= 162 keV) and for SPECT imaging (Eγ = 159 keV) using a DOTA-folate conjugate.
av
X
X
X
X

89
Zr immuno-PET of epithelial ovarian cancer
Sai Kiran Sharma, Brian Zeglis, Kuntal Sevak, Jason Lewis, Frank Wuest
p638–639
Objective: To develop an immuno-PET strategy for in vivo evaluation of CA125 expression in epithelial ovarian
cancer.
Development of HDD kit for preparation of liver cancer therapeutic agent Re-188-HDD/lipiodol
Vinay Kumar Banka, Sung-Hyun Moon, Sudhakara Reddy Seelam, Yun-Sang Lee, Jae Min Jeong
p639
Lipiodol solution of 188 Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithioacetate ( 188
Re-HTDD) was
developed for liver cancer therapy [1–3]. However, formulation of it is difficult due to multi-step syntheses and low
labeling yield. We synthesized a new compound 4-hexadecyl-4,7-diaza-1,10-decanedithioacetate (HDD) to solve
the problems. HDD was synthesized from N,N′-bis-(2-hydroxyethyl)ethylenediamine. BOC protection, thioacetate
introduction, deprotection of BOC, and conjugation with 1-iodohexadecane afforded the final product.
177
Lu-DOTA-DIISAVVGIL: Labelling, quality controls and in-vitro assays
N. Nevares, A. López Bularte, M. Trotta, J. Perez, A. Zapata, S. Michelin, J. Crudo
p639
HER 2 receptors (human epidermal growth factor receptor type 2) are over expressed in various human cancers
including breast and ovarian cancers. Synthetic peptides bind to these receptors with high affinity and specificity.
Labelled peptides with gamma or beta negative radionuclides may be useful candidates for tumour imaging or for
potential use in radionuclide therapy of cancer. The aim of this work was to label DOTA-DIISAVVGIL (HER 2
peptide) with Lu-177 locally produced in the RA 3 research reactor (Argentina) and carry out quality controls and in-vitro
assays.
Novel, multivalent tracers targeting prostate cancer biomarkers
Rajendra Bandari, Tamila Stott Reynolds, Zongrun Jiang, Charles Smith
p639–640
Gastrin-releasing peptide receptors (GRPR), prostate-specific membrane antigen (PSMA), and α β 3
integrin are
identifying biomarkers being investigated as possible tools for molecular targeting and diagnosis of prostate cancer
via PET or SPECT scintigraphy. The aim of this study was to investigate and compare the usage of new
multipurpose, bivalent [DUPA-6-Ahx-( 64
Cu-NODAGA)-5-Ava-BBN(7–14)NH ] and [RGD-Glu-[ Cu-NO2A]-6-Ahx-v
2
64
X
X
X
X

2
RM2] radioligands for prostate cancer imaging. Methods: Conjugates were prepared by solid-phase peptide
synthesis, purified by reversed-phase high-performance liquid chromatography, metallated with 64
CuCl 2
and
nat
CuCl , and characterized by electrospray ionization–mass spectrometry.
2
89
Zr labeling and preliminary evaluation of a trimeric RGD peptide based on a novel
siderophore derived chelating scaffold
Chuangyan Zhai, Peter Knetsch, Dominik Summer, Christine Rangger, Hubertus Haas, Roland
Haubner, Clemens Decristoforo
p640
89
Within the last years Zr has attracted increasing attention as long lived PET radionuclide. So far the bifunctional
chelating system employed for 89
Zr-applications is desferrioxamine B (DFO). Fusarinine C (FSC), a cyclic peptide
siderophore, could be an alternative with potentially higher stability due to its cyclic structure, having complexing
properties comparable to DFO. As proof of principle in this study 89
Zr-labelling of RGD-derivatised FSC, the
optimization of analytical procedures and preliminary evaluation of this compound are reported.
Enabling simultaneous imaging and treatment with the theragnostic radionuclide Tin-117 m
Suresh C. Srivastava
p640
The high-LET conversion electron (C.E.) emitter Sn-117 m (t ½
14 d, γ 159 keV, 86%) shows considerable promise
for the non-invasive molecular imaging and treatment of inflammatory diseases including cancer, and of
atherosclerosis caused by vulnerable plaques (VP) in the coronary and carotid arteries that when ruptured cause
significant cardiac events (~70%) leading to MI and sudden death. The C.E. from Sn-117 m is ideal for treating
VPs, as their discrete range in tissue (~300 μm) is approximately the same as the VP thickness in human carotid
and coronary arteries.
Targeting Gastrin-Releasing Peptide Receptor-Positive Tumors using Yttrium-86 labeled
DOTA-Bombesin(7-14) Analogs
N. Bandara, K. Cherukuri, S. Krieger, J. Parry, S.E. Lapi, B.E. Rogers
p640
The gastrin-releasing peptide receptor (GRPR) is overexpressed on a variety of human cancers including breast
and prostate. Bombesin (BN) is a fourteen amino acid neuropeptide that binds with high affinity to GRPR. Our
laboratory was amongst the first to evaluate BN analogues radiolabelled with positron-emitting radionuclides for
imaging by positron-emission tomography (PET). The goal of this study was to evaluate DOTA-linker-BN(7–14)
analogues radiolabelled with 86
Y (t +
86
1/2
= 14.7 h, β = 33%, E avg
= 664 keV) to determine the effect of using Y in
place of 64
Cu on tumor and normal tissue uptake.
X
X
X

67
Synthesis and evaluation of [ Ga]-AMD3100; A novel imaging agent for targeting chemokine
receptor CXCR4
Ayoub Aghanejad, Amir R. Jalilian, Yousef Fazaeli, Behrouz Alirezapoor, Mehraban Pouladi, Davoud
Beiki, Stephan Maus, Ali Khalaj
p640–641
67
In order to develop a possible CXCR4 imaging agent for oncological scintigraphy, [ Ga]labeled 1,1′-[1,4-
phenylenebis(methylene)] bis-1,4,8,11-tetraazacyclo-tetradecane ([ 67
Ga]-AMD3100) was prepared using
[ 67
Ga]GaCl 3
and AMD-3100 for 2 h at 50 °C (radiochemical purity: >95% ITLC, >99% HPLC, specific activity:
1800–2000 TBq/mmol) in acetate buffer. Stability of the complex was checked in presence of human serum (37 °C)
and in final formulation for 4 days. The biodistribution of the labeled compound in vital organs of wild-type Sprague–
Dawley rats were determined and compared with that of free Ga 3+
cation up to 48 h.
68
Ga-labelled curcuminoids complexes: Characterization of potential radiotracers for imaging
of Alzheimer's disease
Mattia Asti, Erika Ferrari, Stefania Croci, Giulia Atti, Sara Rubagotti, Michele Iori, Pier C. Capponi,
Alessandro Zerbini, Monica Saladini, Annibale Versari
p641
18 99m
Introduction: Curcumin and curcuminoids complexes labelled with F or Tc have recently shown their potential
as diagnostic tools for Alzheimer's disease. Herein, 68
Ga-labelled complexes with curcumin (CUR) and two
curcuminoids, namely diacetyl-curcumin (DAC) and bis-dehydroxy-curcumin (bDHC), were synthesized and
characterized. Materials and methods: The radiotracers were prepared by reacting 68 Ga 3+
obtained from a
68 Ge/ 68
Ga generator with 1 mg/ml curcuminoids solutions. Reaction parameters (precursor amount, reaction
temperature, and pH) were optimized in order to obtain high and reproducible radiochemical yield and purity.
Influence of different chelators on the radiochemical properties and imaging capabilities of a
68-gallium labelled bombesin analogue
Mattia Asti, René Martin, Ralf Bergmann, Michele Iori, Pier C. Capponi, Giulia Atti, Sara Rubagotti,
Albert Brennauer, Marco Müller, Paola A. Erba, Annibale Versari
p641
The radiolabelled bombesin analogue AMBA shows high potential for diagnosis and treatment of prostate and
breast cancer but the influence of different chelators has not been explored so far. In this study, we synthesized
AMBA analogues linked to the most common used chelators DOTA, NOTA and NODAGA and compared their
reactivity and in vivo biodistribution after labelling with 68-gallium.
Albumin-based nanoformulation for prostate-specific membrane antigen (PSMA)
X
X
X

Sangeeta R. Banerjee, Baiqi Wang, Mrudula Pullambhatla, Catherine A. Foss, Martin G. Pomper,
Russell H. Morgan
p641–642
Targeted delivery of nanocarriers demonstrated improved efficacy of chemotherapy while reducing its systemic
toxicity. Here we report a targeted albumin-based multimodality nanoformulation for potential imaging and
therapeutic delivery to prostate cancer. For targeting, we have selected PSMA, a well-established biomarker, which
exhibits high expression in primary and metastatic prostate cancer and in most solid tumor and tumor
neovasculature. The albumin nanoformulation was prepared by covalent conjugation of fluorescein for cell imaging,
DTPA for 111
In-labeling for SPECT, Glu-Lys urea for PSMA targeting and NIR dye 800 CW for in vivo optical
imaging respectively via amide bond formation and ultrafiltration after each conjugation step and characterized by
mass spectroscopy and gel electrophoresis.
68 2
Single vial kit for preparation of Ga-NODAGA-E[c(RGDfK)] as a PET radiotracer
Sudipta Chakraborty, Rubel Chakravarty, H.D. Sarma, Ashutosh Dash
p642
68
Cyclic RGD (Arg-Gly-Asp) peptides radiolabeled with Ga have great potential for the noninvasive monitoring of
tumor growth, metastasis and therapeutic response. Single vial kits of NODAGA-E[c(RGDfK)] 2
(NODAGA = 1,4,7-
triazacyclononane,1-glutaric acid-4,7-acetic acid, E = Glutamic acid, R = Arginine, G = Glycine, D = Aspartic acid, f
= phenyl alanine, K = lysine) were formulated for radiolabeling with 68
Ga using 10 μg of peptide conjugate.
Radiolabeling was performed within 5 min at room temperature by simply mixing the content of the kit vial with
68
GaCl (0.5 mL, ~185 MBq).
3
Tumor pretargeting with antibody fragments and the Diels–Alder reaction
Sander M.J. van Duijnhoven, Raffaella Rossin, Sandra M. van den Bosch, Michael Wheatcroft, Peter
Hudson, Marc S. Robillard
p642
Cancer RIT with radiometal-labeled mAb fragments and peptides is hampered by low T/K ratios due to radiometal
sequestration in the kidney. To overcome this drawback, we evaluated whether pretargeting based on the Diels–
Alder reaction can reduce the kidney dose compared to directly labeled mAb fragments. An anti-TAG72 diabody
(AVP04-07) was functionalized with trans-cyclooctene (TCO) via Lys conjugation. The biodistribution of 125
I-AVP04-
07 carrying respectively 0, 1.8 and 3.5 TCOs/diabody (35 μg/mouse) was evaluated in LS174T xenografted mice:
47 h post- 125 I-diabody administration, 177
Lu-tetrazine was injected (0.1–10 eq.
64
A novel radiometric phosphatidylserine (PS) binding assay based on [ Cu]Cu-NOTA-annexin-
V
Christian Foerster, Amanda Perreault, Melinda Wuest, Cody Bergman, Frank Wuest
X
X
X

p642–643
Objective: [ 99m
Tc]Tc-HYNIC-annexin-V is currently the state-of-the-art radiotracer for in vitro and in vivo imaging of
early stage apoptosis. Here we report the application of 64
Cu-labeled annexin-V as radiotracer in a novel
radiometric binding assay to assess various phosphatidylserine (PS)-binding peptides.
How technetium could help some PET nuclear chemistry technology: application of Tc-99 NMR
for analysis of O-18 content in water
Valery Tarasov, Gayane Kirakosyan, Konstantin German
p643
The method for 17 O and 18
O analysis is proposed being based on addition of isotopically saturated water samples
to solid M 99
TcO 4 (M = NH 4
or Na) followed by quantification of 99
Tc-NMR spectrum fine structure in the coordination
sphere of pertechnetate. The isotopic shifts 16/17 Δ, 16/18 Δ NMR 99
Tc and the constants of spin-spin interaction of
isotopomers: Tc 16
O 17
O − , Tc 16
O 18 O − 16
2
2
3
,Tc O 17 − 16
17 18 3
O , Tc O 2
O O − , Tc 16
O 18
O −
2
2
are determined. In the solution
of ammonium pertechnetate for the anions Tc 16
O 18 3
O and Tc 16
O 17 −
3
O at the temperature interval 278–333 К the
isotopic shift is given by liner dependencies 16/18 Δ = −0.616 + 6.45 × 10 −4 Т (ppm) and 16/17 Δ = −0.302 + 2.67 × 10
−4
Т (ppm), correspondingly.
68
Receptor-mediated binding of [ Ga]tilmanocept by mesangial cells
Carl K. Hoh, Zhengtao Qin, David J. Hall, David R. Vera
p643
Introduction: Glomerular mesangial cells regulate glomerular blood flow, and provide structural support and immune
surveillance of invading pathogens. This latter function is consistent with the role of CD206, the receptor for
[99mTc]tilmanocept.
64
Development of analytical methods for investigation of new Cu(II) complex with HL-1 –
Potential anticancer agent
D. Kludkiewicz, M. Maurin, P. Garnuszek, Anne-Katrin Bachon, Patrick Gamez, R. Mikolajczak
p643
Complex of 2-tert-butyl-6-(pyridine-2-ylhydrazonomethyl)phenol (HL-1) with copper(II) is highly cytotoxic and may
be potentially used for cancer treatment. The complex was characterized with instrumental techniques and in vitro
assays. Replacing copper(II) with radioisotope 64
Cu(II) may give better insight into pharmacokinetics and
biodistribution of this complex. However, different approach towards analysis of radioactive complex is required.
177
X
X
X
X

177
Comparison of the internalization results of two minigastrin analogs labelled with Lu
A. López Bularte, N. Nevares, M. Trotta, J. Perez, A. Zapata, S. Michelin, J. Crudo
p643–644
Radiolabelled peptides with beta negative emitters are used in peptide receptor radionuclide therapy (PRRT) for the
treatment of various tumours. Radiolabelled analogues of cholecystokinin/gastrin family showed promising results
for PRRT in tumour expressing CCK2 receptors.
11 11
Effects of Gly /DAla -replacement in GRPR-antagonist based radioligands
E. Lymperis, T. Maina, A. Kaloudi, E.P. Krenning, M. de Jong, B.A. Nock
p644
Radiometallated bombesin (BBN) analogs deliver diagnostic or therapeutic radiation specifically to GRPR-positive
tumors, such as prostate and breast cancer. Based on the reported higher bioavailability of DAla 11
-substituted BBN
analogs, we developed two new GRPR-antagonists, SB3 = DOTA-PABZA-DIG-[DPhe 6 ,Leu-NHEt 13
]BBN(6–13) and
SB4 = [DAla 11 ]SB3. We were interested to reveal potential advantages of this single Gly 11 /DAla 11
-replacement by
comparing the biological profiles of the two analogs and their 111
In-radioligands.
Radiolabelling and preliminary biological evaluation of NOTA-cRGD dimer labelled with Ga-68
Dana Niculae, Ioana Esanu, Filip Puicea, Cosmin Mustaciosu
p644
The α v β 3
integrin receptor, expressed on tumor cell membranes can be preferentially targeted by peptides
containing the RGD sequence, resulting in a versatile cell recognition system. NOTA-SCN-Bn-E-[c(RGDyK) 2
] was
labelled with Ga-68 and tested for radiolabelling yield, purity, stability, in vitro binding and ex vivo biodistribution.
The radiolabelling was performed using an automated system with inline quality control and Ga-68 eluate from a tin
oxide based Ge-68/Ga-68 generator, purified and concentrated to 400 MBq in 0.1 mL water on an anionic
exchanger resin.
A tri-modal tilmanocept for sentinel lymph node mapping
Zhengtao Qin, Carl K. Hoh, David R. Vera
p644–645
Introduction: We report a novel method to prepare 68 Ga and 99m
Tc dual-labeled IRDye800CW-tilmanocept, a
sentinel lymph node (SLN) targeting agent, for tri-modal molecular imaging.
89
X
X
X
X

89
In vivo imaging of Zr-labeled poly(2-ethyl-2-oxazoline)s and poly(ethylene glycol)s
T. Verbrugghen, L. Wyffels, B. Monnery, R. Hoogenboom, S. Staelens
p645
Poly(2-alkyl-2-oxazoline)s (PAOx) are a class of versatile biocompatible polymers with promising applications in
drug development.
In-111 labeled peptides targeting the estrogen receptor for theranostic of cancer
Filipe Vultos, Célia Fernandes, João D.G. Correia, Isabel Santos, Lurdes Gano
p645
Estrogen receptor (ER) expression is considered one of the most important biomarkers in breast cancer (BC)
management. Therefore the search for novel ER targeting ligands has been a challenging task [1].
Active targeting with Y-90 radiolabelled octreotate functionalized AGuIX ultra-small nano
particles
M. Maurin, U. Karczmarczyk, P. Garnuszek, R. Mikołajczak, A. Sawicka, C. Truillet, F. Lux, A.
Clabaut, O. Tillement
p645
AGuIX nano particles consist of polysiloxane backbone with attached DOTA chelators. These particles have been
characterized for imaging properties after radiolabelling with 111 In or 68
Ga within COST TD1004 collaborations.
Parent AGuIX particles were functionalized with octreotate (TATE) after conjugation of peptide to terminal ammine
of particle. The aim of our work was to label them with 90
Y and to evaluate their therapeutic potential.
Radiometals development in the U.S. Department of Energy Isotope Program
Dennis R. Phillips
p645–646
Metallic radioisotopes are used in medicine, biology, environmental research, nuclear forensics, basic research and
other important fields of scientific endeavor. The practice of nuclear medicine depends upon the reliable availability
of radioactive isotopes with the proper characteristics and sufficient quantities to support diagnostic and therapeutic
research and clinical applications. This presentation will provide a description of the congressionally mandated role
of the Isotope Program in the Office of Nuclear Physics in the U.
Cyclotron based production of high specific activity [197(m)Hg]HgCl2
X
X
X
X

2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650

2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650

Recomendados

Recomendados

Más contenido relacionado

La actualidad más candente

La actualidad más candente (20)

Similar a 2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650

Similar a 2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650 (20)

Más de Konstantin German

Más de Konstantin German (20)

Último

Último (20)

2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650