1. MS-325 is an albumin-targeted gadolinium contrast agent that highlights inflamed vessel walls and facilitates plaque imaging. It provides prolonged enhancement of the vessel wall and lumen, allowing for high resolution detection of plaque burden.
2. Studies show MS-325 provides strong enhancement of vessel walls adjacent to plaques due to increased capillary volume and binding to extravasated albumin in the vessel wall. This allows for detection and potential quantification of atherosclerotic plaques.
3. Experimental fibrin-targeted contrast agents EP-1242 and EP-1873 rapidly enhance arterial and venous blood clots in animal models, demonstrating potential for assessing thromboembolic risk and monitoring clot resolution with
4. 4
Jeffrey H. Maki1,2
, Gregory J. Wilson1
,
Randall B. Lauffer3
, Robert M. Weisskoff3
,
Chun Yuan2
1 - Puget Sound VAHCS, Seattle, WA
2 - University of Washington, Seattle, WA
3 - EPIX Medical, Cambridge, MA
Vessel Wall Enhancement with MS-325
MRI Facilitates Plaque Detection and
Characterization
5. 5
Vessel Wall Enhancement
with MS-325
• Atherosclerosis = inflammation
• Leaky capillaries supplying vessel
wall
– Increased albumin conc. in wall
• Consistent enhancement of wall in
patients with MS-325
• Implications for stenosis
identification and quantitation (and
plaque burden)
• Enhancement may correlate with
risk of rupture
Aorta
Right Iliac
Artery
Vessel
Wall
Vessel
Wall
Courtesy of: Dr. J Maki (UW/Puget S VA)
8. 8
Results
• Strong wall enhancement with MS-325 because of
increased capillary volume and binding to
extravasated albumin
• Low signal between wall and lumen represents
atherosclerotic plaque.
• Prolonged enhancement of wall and lumen allows
high resolution detection of plaque burden
• Potentially straightforward method of plaque
visualization and quantification
• ? Follow statin therapy
9. 9
Pharmacological trigger
histamine = vasoconstrictor -> increases mechanical force on fibrous cap -> plaque
disruption
Russells viper venom -> triggers blood clotting cascade
fresh thrombus
lipid core?
thin fibrous cap?
fresh thrombus
vasoconstriction
pre-trigger
post-trigger disrupted plaque
T2w
Visualization of Plaque Rupture in Rabbit Model
Johnstone MT, Botnar RM, Perez AS, Stewart R, Quist W, Hamilton J, Manning
WJ. In Vivo Magnetic Resonance Imaging of Experimental Thrombosis in a
Rabbit Model. Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1556-60.
Courtesy: Johnstone, Botnar, Manning: BIDMC
11. 11
Direct Clot Detection with Fibrin-
Targeted Contrast Agent
• Fibrin targeting lead discovered in a collaboration with
Dyax
• MR contrast agents EP-1242 and EP-1873 resulted from
extensive modifications by EPIX of the original leads
• Elimination profile similar to Magnevist®
EP-1242 Enhanced Carotid Clot in Guinea Pig
In collaboration with Z. Fayad, Ph.D., Mt. Sinai, New York
12. 12
To be annotated, final copy will be printed high definition
Post Gd-BSA (angiography)
Pre contrast
1 minute post EP-1873
36 minute post EP-1873
Jugular
thrombus
Rabbit Carotid
thrombus
Jugular
thrombus
Carotid
thrombus
In collaboration with E. Kent Yucel, Lee Zhou (?) Brigham & Women’s, Boston
16. 16
Summary
• Prototype clot-enhancing agents for MRI
– High binding affinity and selectivity to human fibrin
– Rapid Enhancement of arterial and venous clots
– Good in vivo clot uptake and enhancement
– No effects on clotting cascade
• Thrombotic consequences of plaque rupture
directly visible on standard MR scans
– Potential for assessing thromboembolic risk in a
variety of vascular beds
– Follow clot resolution after treatment
administration?
Notas del editor
<number>
<number>
Long segments of wall enhancement seen, even in relatively normal vessels per angiography
Wall thickness greatest in areas of greatest atherosclerosis burden