PHOTODYNAMIC THERAPY OF TUMORS - EFFECTS OF HEMATOPORPHYRIN DERIVATIVE ON NORMAL RAT INTESTINE

Hematoporphyrin derivative (HpD) is a complex mixture of dicarboxylic porphyrins in addition to dimers, oligomers and aggregates of variable sizes. The ability of this mixture(and enriched preparations thereof) to be retained by tumors and to sensitize them to destruction by ligh t has led to worldwide studies of the treatment modality called photod ynamic therapy (PDT). Understanding how PDT affects normal tissues sur rounding the tumor is of crucial importance. Prior studies have docume nted that normal intestinal blood flow can be disrupted by HpD PDT. In addition, mucosal and submucosal damage to normal rat jejunum was obs erved following HpD PDT. The present study was designed to correlate t he above observed changes with local levels of porphyrins. Three group s of Fischer 344 rats were injected with 0 (controls), 10 or 20 mg HpD /kg body weight. Twenty-four hours after the drug was injected, jejuna l segments were excised and blood samples taken. Jejunal contents were obtained by saline perfusion and analyzed for porphyrins alongside th e jejunal homogenates and the bloods. Jejunal segments of animals inje cted with 10 or 20 mg HpD/kg b.w. had porphyrin levels some 4- and 9-f old above controls (controls m +/- S.D. = 0.25 +/- 0.12 mu g/g wet wei ght). For each injected dose the jejunal perfusates contained 2- and 3 -fold higher levels of porphyrins (in transit) as the controls (contro ls, m +/- S.D. = 1.48 +/- 0.66 mu g/g w.w.). In the general circulatio n, only 0.6% or 0.4% of the respective injected doses remained. After HpD i.v. injections, high levels of porphyrins were found in the small intestine and in transit. These facts, if coupled with an active ente ro-hepatic circulation, may lead to serious normal tissue damage follo wing PDT.