This document discusses the history and current state of photodynamic therapy (PDT) for cancer treatment. It covers the basics of PDT, including photosensitizers, light sources, the photodynamic reaction, and clinical applications for various cancer types. It also touches on dosimetry challenges, the potential for nanotechnology to advance PDT, and using PDT for theranostics and generating anti-cancer immune responses. In summary, PDT utilizes photosensitizing drugs activated by light to induce oxidative stress and kill cancer cells, with applications across dermatology, neuro-oncology, and other fields, though challenges remain in optimizing light doses and monitoring treatment responses.

1. PHOTODYNAMIC THERAPY :
ONCOLOGIC HORIZONS
Kanmani Velarasan .S
CMC Vellore
2014 Future oncol

2. HISTORY
• Hippocrates – practitioner of helio(light)
therapy
• Finson – Nobel prize in 1903 – treating
diseases with light
• Oscar Raab – “photodynamic reaction” – start
of 20 th century

3. 1. Photosensitisers
2. Light sources
3. Photodynamic reaction
4. Clinical application
5. Theranostics
6. Future prospective

4. Photosensitizers
• Porphyrins – backbone
Reliable generation of oxygen Rapid pharmokinetics
Synthetic purity Fluorescence
Synthetic ease Amphilicity
Storage stability Targeting
Lack of dark toxicity Painless
Lack of toxic degradation products Minimal skin photosensitivity
Administrative ease Commercially available , regulatory
agency approval
Optical window

5. • Hematoporphyrin derivative :
• 1970’s
• Non toxic/ IV/ painless/ OP basis/
• Longer illumination time and avoidance of
sunlight for longer periods

6. • ALA :
• Inactive prodrug/ topical, oral or IV/ less
photosensitivity/ high yield of oxygen / short
illumination time
• Painful – requires interruption
• Methylaminolevulonate (MAL) and
hexylamino levulinate (HAL)

7. • Temoporfin :
• Synthetic purity/ high oxygen production /
penetration upto 1 cm/
• Rapid ablation – morbidity/ painful – requires
anaesthesia/ fibrosis
• Talaporfin :
• Clinical and commercial success
• High quantum yield
• Photosensitivity - upto weeks

8. LIGHT SOURCES
• Each PS has specific wavelegth and intensity of
light
• Clinically 400-800 nm
• Blue light – 400 nm – 1-2 mm
• Green light – 500 nm – 5 mm
• Red light – 600 nm – 1 cm

9. • Sunlight – broad spectrum. Unintentional
sunlight – morbidity
• Arc lamps and lasers.
• Fiberoptics
• LED

10. Photodynamic reaction
• Type 2 reaction – oxygen – singlet oxygen (20-200
ns) – destruction
• Type 1 reaction – hydroxyl radicals and
superoxide ions (Fenton reaction)
• Type 3 – direct action
• Fluorescence – demarcation of lesion

11. • Photosensitizers accumulate in cellular and
subcellular membranes
• Preferential accumulation in tumor and
neovasculature
• Does not intercalate with DNA – non
mutagenic

12. • Cytotoxicity : Insult – heat shock proteins –
anti oxidants
• PDT – apoptosis and/or necrosis
• Necrosis – immune system
• Vascular effects:
• Stop/ diminish blood supply/platelet
aggregation – hypoxia
• PS accumlates in neovascularity

13. • PDT – immune upregulation
• Tumor vaccine – area of research
• Activated immune cells travel to nodes –
ablation of metastatic lesions

14. CLINICAL APPLICATIONS
• Skin : allison et al – in situ/ invasive palpable
squamous and basal cell cancers
• MAL – Europe – BCC
• Nodular lesions respond less
• Neurologic : Adjuvant (photofrin)
• Fluorescence – Fluorescent guided resection
• Stummer et al – ALA based resection +
photofrin based PDT – doubled survival and
control

15. • Head and Neck :
• Salvage of local recurrences and early lesions
• Biel et al – early vocal cord cancer – 1-2
sessions – superior voice preservation
• Pulmonary :
• Prolonged palliation in endobronchial
obstruction
• Early stage NSCLC
• Tried in malignant mesothelioma

16. • GI : Palliation in obstructing oesophageal
cancers and cholangiocarcinoma
• Early stage (Tis/T1/T2)
• Barrett’s oesophagus – great success. Stricture
20 %
• HCC : prolonged illumination through
implantable LED
• Anal sphincter : salvage sphincter

17. • Gynaecology :
• Non invasive cervical intraepithelial neoplasia,
vulval and vaginal intraepithelial neoplasia
• ALA cream and IV photofrin
• GU :
• Bladder – high morbidity . Illumination
difficult
• HAL – fluorescent guided resection
• Prostate – lutetium texaphrin and WST 11 .
Deep penetration. Interstitial with LEDs tried.
High complications (fistula, incontinence)

18. DOSIMETRY
• Actual light dose – not available despite
advanced calculations
• Failure/ normal tissue toxicity
• Concentration in tissues and tumor
• Variables – light dose, drug dose and oxygen
levels
• Lack of accurate dosimetry also holds back –
radiofrequency ablation , microwave and
cryotherapy

19. • Nanotechnology :
• Bound to naturally occuring plasma protein
nanoparticles
• Nanoparticle carriers
• PS + antibodies/ chemotherapy/targeted
agents/ poisons – lethality
• Nanoparticles + PS + biosensors –
personalised cancer therapy

20. • Theranostics :
• PS – radiosensitiser
• PS + chemotherapy – photochemical
internalisation
• Imaging qualities

21. • Future prospective
• Complementary
• Option for optimal care
• Fluorescence and photo diagnosis
• PDT – cancer vaccines