Biodistribution and Pharmacokinetics of a Carborane-Containing Porphyrin in the Hamster Cheek Pouch (HCP) Carcinogenesis Model

SCHWINT AE; KREIMANN EL; MIURA M; ITOIZ ME; GARAVAGLIA RN; BATISTONI D; CODERRE JA

Osaka International Convention Center, Osaka, JAPAN.

Congreso; Ninth International Symposium on Neutron Capture Therapy for Cancer.; 2000

INTERNATIONAL SOCIETY FOR NEUTRON CAPTURE THERAPY

We proposed and validated the hamster cheek pouch carcinogenesis model of oral cancer for BNCT research in a separate study. We herein present the biodistribution and pharmacokinetics of a lipophilic, carborane-containing tetraphenylporphyrin, CuTCP, in this model. We administered CuTCP i.p. as a single dose of 32 mg/g bw (10 mg B/g bw) or as 4 doses of 32 mg/g bw over 2 days. Blood (Bl) and tissues were sampled at 3, 6, 12, 24, 48 and 72 hours in the single dose protocol and at 1-4 days after the last injection in the multidose protocol. The tissues sampled were tumor (T), precancerous tissue surrounding tumor, normal pouch (N), skin, tongue, cheek and palate mucosa, liver, spleen, parotid gland and brain. Boron analysis was performed by ICP-AES. The maximum individual B ratios for the single dose protocol were T/N: 32.7/1 and T/Bl: 31.8/1. The B value in tumor reached a maximum of 43.8 ppm. However, the mean tumor value of 16 ± 14.3 ppm fell short of therapeutically useful levels. The multidose protocol maximum ratios were T/N: 53.33/1 and T/Bl: 3633.3/1. The maximum absolute B value in tumor reached 106.40 ppm. The mean value in tumor at 3 days was 68.02 ± 25.02. Absolute and relative maximum and average B values markedly exceeded the therapeutic threshold values.