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 light has led to worldwide studies of the treatment modality called photodynamic therapy (PDT). Understanding how PDT affects normal tissues surrounding the tumor is of crucial importance. Prior studies have documented that normal intestinal blood flow can be disrupted by HpD PDT. In addition, mucosal and submucosal damage to normal rat jejunum was observed following HpD PDT. The present study was designed to correlate the above observed changes with local levels of porphyrins. Three groups 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, jejunal segments were excised and blood samples taken. Jejunal contents were obtained by saline perfusion and analyzed for porphyrins alongside the jejunal homogenates and the bloods. Jejunal segments of animals injected with 10 or 20 mg HpD/kg b.w. had porphyrin levels some 4- and 9-fold above controls (controls m +/- S.D. = 0.25 +/- 0.12 micrograms/g wet weight). For each injected dose the jejunal perfusates contained 2- and 3-fold higher levels of porphyrins (in transit) as the controls (controls, m +/- S.D. = 1.48 +/- 0.66 micrograms/g w.w.). In the general circulation, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Department, St. Vincent Medical Center, Toledo, OH 43608.
M
M
Kreimer-Birnbaum
G M
GM
Garbo
R W
RW
Keck
S H
SH
Selman
C M
CM
Foss
B M
BM
Shiff
D000818:Animals; D017324:Hematoporphyrin Derivative / Q000494:pharmacology*; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000293:injuries; D007583:Jejunum / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D010477:Perfusion; D010778:Photochemotherapy / Q000009:adverse effects; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow / Q000187:drug effects
D011166:Porphyrins; D017324:Hematoporphyrin Derivative