SYNTHESIS OF A NICKEL TETRACARBORANYLPHENYLPORPHYRIN FOR BORON NEUTRON-CAPTURE THERAPY - BIODISTRIBUTION AND TOXICITY IN TUMOR-BEARING MICE

Nickel-2,3,7,8,12,13,17,18-octaacetic 15,20-tetra-[3-carboranyl-methox yphenyl]-porphyrin octamethylester (NiTCP) was given in a Cremophor EL , a polyethoxylated castor oil, and propylene glycol emulsion to BALB/ c mice bearing transplanted s.c. KHJJ mammary carcinomas. A total dose of 244 mu g NiTCP/gram body weight (gbw) (54 mu g B/gbw) was given in 6 i.p. injections over a 32 hr period. Observations of behavior and c hanges in body weight and chemical and hematological blood tests indic ated little or no toxicity from NiTCP over a period of 6-90 hr after i njections. Boron concentrations near tumor margins were 160-180 mu g B /g at 41-90 hr after the last injection. Tumor:normal brain boron conc entration ratios reached approx. 10:1 and tumor:blood ratios reached a pprox. 250:1 after 4 days. There was no evidence of thrombocytopenia o r other potentially important toxicities. Our findings place NiTCP amo ng the leading candidates for pre-clinical experiments aimed toward im provement upon the compounds being tested for boron neutron-capture th erapy of glioblastoma multiforme. (C) 1996 Wiley-Liss, Inc.