Photodynamic therapy of a transplanted pancreatic cancer model using meta-tetrahydroxyphenylchlorin (mTHPC)

Abstract

Pancreatic cancer is difficult to treat, even for rumours localized to the pancreas. Photodynamic therapy (PDT) is a non-thermal technique for producing localized tissue necrosis with light after prior administration of a photosensitizing drug and it could have a role in the local treatment of these cancers. We studied PDT in a transplanted cancer in the hamster pancreas using the photosensitizer mTHPC (meta-tetrahydroxyphenylchlorin). Fluorescence microscopy showed maximum levels of mTHPC in normal pancreas 2-4 days after sensitization and in tumour at 4-5 days. For PDT, animals were given 0.1 or 0.3 mg kg-1 mTHPC and the tumour was treated at laparotomy 2 or 4 days later with red light (50 J at 650 nm, continuous or fractionated) delivered via a single fibre touching the tumour surface. The maximum zone of tumour necrosis (seen 3 days after PDT) was 8.7 mm in diameter with continuous irradiation, increasing to 12.4 mm with light fractionation (four equal fractions with 3 min between fractions). The main complication was sealed duodenal perforation, seen in 3 of 16 animals, probably due to inadequate shielding of the duodenum from the light. The duodenal problems seen in hamsters are unlikely to cause trouble in the much thicker human duodenum. PDT tumour necrosis in this animal model has now been shown with a range of photosensitizers, but mTHPC is attractive as it is likely to produce the largest volumes of necrosis around each treatment point with short light exposure times. This technique could have a role in the treatment of localized cancers of the pancreas in patients unsuitable for surgery and can now be considered for preliminary clinical trials.