Document Detail


Photodynamic therapy using verteporfin photosensitization in the pancreas and surrounding tissues in the Syrian golden hamster.
MedLine Citation:
PMID:  17449962     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIM: 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.
CONCLUSION: 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.
Authors:
Lakshmana Ayaru; Johannes Wittmann; A J Macrobert; Marco Novelli; Stephen G Bown; Stephen P Pereira
Publication Detail:
Type:  Journal Article     Date:  2007-04-18
Journal Detail:
Title:  Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]     Volume:  7     ISSN:  1424-3903     ISO Abbreviation:  Pancreatology     Publication Date:  2007  
Date Detail:
Created Date:  2007-05-14     Completed Date:  2007-07-05     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  100966936     Medline TA:  Pancreatology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  20-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Colon / drug effects,  pathology
Cricetinae
Duodenum / drug effects,  pathology
Female
Injections, Intravenous
Liver / drug effects,  pathology
Mesocricetus
Mesoporphyrins / administration & dosage
Necrosis
Pancreas / blood supply,  drug effects*,  pathology
Photochemotherapy*
Photosensitizing Agents / administration & dosage,  pharmacokinetics,  toxicity*
Porphyrins / administration & dosage,  pharmacokinetics,  toxicity*
Grant Support
ID/Acronym/Agency:
G0801588//Medical Research Council
Chemical
Reg. No./Substance:
0/Mesoporphyrins; 0/Photosensitizing Agents; 0/Porphyrins; 129497-78-5/verteporfin; FU21S769PF/temoporfin

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