Intraperitoneal photodynamic therapy in the rat: comparison of toxicity profiles for photofrin and MTHPC.
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.
Veenhuizen
R B
RB
Division of Experimental Therapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Ruevekamp-Helmers
M C
MC
Helmerhorst
T J
TJ
Kenemans
P
P
Mooi
W J
WJ
Marijnissen
J P
JP
Stewart
F A
FA
D000818:Animals; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D006414:Hematoporphyrin Photoradiation / Q000379:methods*; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008652:Mesoporphyrins / Q000627:therapeutic use / Q000633:toxicity*; D010529:Peritoneal Cavity; D010778:Photochemotherapy / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use / Q000633:toxicity*; D051381:Rats; D013047:Specific Pathogen-Free Organisms
D008652:Mesoporphyrins; D011838:Radiation-Sensitizing Agents; D017323:Dihematoporphyrin Ether; C072269:temoporfin