Synthesis of copper octabromotetracarboranylphenylporphyrin for boron neutron capture therapy and its toxicity and biodistribution in tumour-bearing mice

The British Journal of Radiology
M MiuraD N Slatkin

Abstract

Copper tetracarboranyltetraphenylporphyrin (CuTCPH) is a minimally toxic carborane-containing porphyrin that has safely delivered high concentrations of boron for experimental boron neutron capture therapy (BNCT). Copper octabromotetracarboranylphenylporphyrin (CuTCPBr), synthesized by bromination of CuTCPH, is one of several new minimally toxic analogues of CuTCPH being studied in our laboratory, which could possess comparable or better tumour-targeting properties with enhanced tumour cytotoxicity. Its biodistribution, biokinetics and toxicity in mice with subcutaneous EMT-6 (mammary) or SCCVII (squamous cell) carcinomas were compared with those of CuTCPH. The administration of approximately 200 mg kg(-1) of either porphyrin in six intraperitoneal injections over 2 days had no apparent effect, but administration of approximately 400 mg kg(-1) slightly lowered body weights, elevated alanine and aspartate transaminase activities in blood plasma, and depressed blood platelet counts for several days. Enzymes and platelets returned to normal within 5 days after those injections and body weights returned to normal within 2 weeks. High average concentrations of boron from either porphyrin were achieved in the two tumour models from a...Continue Reading

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Citations

Apr 29, 2008·Critical Reviews in Oncology/hematology·Andrea WittigWolfgang A G Sauerwein
Jan 22, 2011·Lasers in Surgery and Medicine·Ryo HiramatsuM Graça H Vicente
Mar 15, 2013·International Journal of Radiation Biology·Henry M SmilowitzMichiko Miura
Jan 27, 2007·Journal of Medicinal Chemistry·Myoung-Seo KooStephen B Kahl

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