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(Journal Article) |
International journal of cancer 59 (6): 830-6 (1994)
Intraperitoneal photodynamic therapy in the rat: comparison of toxicity profiles for photofrin and MTHPC.
R B Veenhuizen
,
M C Ruevekamp-Helmers
,
T J Helmerhorst
,
P Kenemans
,
W J Mooi
,
J P Marijnissen
,
F A Stewart
ABSTRACT
Toxicity studies for intraperitoneal photodynamic therapy (IPPDT) were performed in Wag/RijA rats, using specially designed light delivery blocks for proper light distribution and light dosimetry. A recently developed photosensitizer mesotetrahydroxyphenylchlorin (mTHPC), excited at 652-nm wave-length, was compared with Photofrin (630 nm). Toxicity profiles for various sensitizer doses, light fluences and time intervals were investigated. A light fluence of 15 J.cm-2 delivered to the entire peritoneum 24 hr after 5 mg Photofrin per kg i.v. induced reversible impairment of intestinal, liver and kidney function. A dose of 0.2 mg mTHPC per kg i.v. followed by 6 J.cm-2 at 72 hr appeared to be equitoxic to the intestines; however, functional tests revealed little effect for this mTHPC-mediated IPPDT regime on liver or kidney. Histology demonstrated focal irreversible damage to the kidneys for both photosensitizers, not reflected in functional impairment. Light doses of 25 to 30 J.cm-2 at 24 hr after Photofrin or 8-12 J.cm-2, 72 hr after mTHPC caused lethal toxicity in the first 2 weeks due to intestinal damage. Higher light doses caused a shock syndrome and rhabdomyolysis resulting in death within 20 hr for both photosensitizers. In conclusion, maximum tolerable schedules for whole-abdomen IPPDT were defined for Photofrin and mTHPC. Both photosensitizers caused similar toxicity profiles depending on drug dose, light fluence and time interval.