Photodynamic therapy using verteporfin photosensitization in the pancreas and surrounding tissues in the Syrian golden hamster.
OBJECTIVE
Photodynamic therapy (PDT) is a potential treatment for locally advanced pancreatic cancer. We aimed to assess the safety of interstitial PDT using verteporfin (benzoporphyrin derivative monoacid A - a novel photosensitizer with a short drug-light interval and limited cutaneous photosensitivity) in the Syrian golden hamster, and compare it to meso-tetrahydroxyphenylchlorin (mTHPC) which we have previously evaluated in preclinical and clinical studies.


METHODS
Verteporfin (2 mg/kg) was administered at laparotomy by inferior vena caval injection (n = 57), with plasma levels quantified at 5, 15, 30, 60 and 240 min, and 24 h. 15 min after photosensitization, tissues (liver, pancreas, duodenum, colon, aorta) were illuminated with 690 nm red laser light (150 mW), at a range of light doses (1-100 J/cm(2)). The PDT effects on the targeted organ and adjacent structures were assessed at post-mortem on days 3 and 21, or at the time of death.


RESULTS
The elimination half-life of verteporfin was 4-5 h. Light doses of 10, 25 and 50 J/cm(2) were safe in the hamster pancreas, liver and colon, respectively, and produced coagulative necrotic lesions of 3 (range 3-4), 10 (9-10) and 7 (7-8) mm diameter. Collagen was resistant to damage and lesions healed mainly by regeneration of normal tissue. At higher light doses, necrosis extended to the edge of organs, sometimes causing sealed duodenal perforations as seen with mTHPC.


CONCLUSIONS
The safety profile of verteporfin is very similar to mTHPC, with the advantages of a shorter drug-light interval and drug elimination time. Phase I clinical studies using this photosensitizer in pancreatic cancer should be feasible.
Ayaru
Lakshmana
L
The UCL Institute of Hepatology, Department of Medicine, Royal Free and University College London Medical School, University College London, London, UK.
Wittmann
Johannes
J
Macrobert
A J
AJ
Novelli
Marco
M
Bown
Stephen G
SG
Pereira
Stephen P
SP
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000473:pathology; D006224:Cricetinae; D004386:Duodenum / Q000187:drug effects / Q000473:pathology; D005260:Female; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008647:Mesocricetus; D008652:Mesoporphyrins / Q000008:administration & dosage; D009336:Necrosis; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000077362:Verteporfin
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; C072269:temoporfin