PHARMACOKINETIC AND TISSUE DISTRIBUTION STUDIES OF THE PHOTOSENSITIZER BIS(DI-ISOBUTYL OCTADECYLSILOXY)SILICON 2,3-NAPHTHALOCYANINE (ISOBOSINC) IN NORMAL AND TUMOR-BEARING RATS

Bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSIN C) is a representative of a group of naphthalocyanine derivatives with spectral and photophysical properties that make them attractive candi dates for photodynamic therapy (PDT). Tissue distributions were studie d in normal and in tumor-bearing rats as a function of time following intravenous injection of isoBOSINC as a suspension in 10% Tween 80 in saline. The dose studied was 0.25 mg/kg of body weight. The compound i soBOSINC was isolated from several tissues and organs, as well as tumo rs and peritumoral muscles and skin, and quantitated by a high-perform ance liquid chromatographic technique. The tumor model, an N-(4-[5-nit ro-2-furyl]-2-thiazolyl)formamide (FANFT)-induced urothelial cell carc inoma, was transplanted into the hind legs of Fischer 344 rats. The dy e was retained in tumors at higher concentrations than in all tissues and organs examined, except for spleen and liver. The highest concentr ation ratio of dye in tumor versus peritumoral muscle (24.5) occurred 9 h after injection. Serum clearance of iso BOSINC showed similar kine tic behavior for both groups of rats, with a t(1/2) of elimination of similar to 10 h. At 7 and 14 days postinjection, the levels of dye fou nd in testes were generally higher than in most other tissues, except spleen and liver. Concentrations of isoBOSINC were either very low or not detectable in rat brain. Trace amounts of the dye were excreted in the urine, and by day 14 approximately 17% of the dose was accounted for in the feces. The significant levels of the drug in tumors, as wel l as the excellent ratios of tumor-to-muscle concentration observed, h ave promising implications for PDT of tumors.