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 total dose of approximately 200 mg kg(-1). The high tumour
boron concentration decreased slowly while concentrations in blood decreased rapidly.
Boron concentrations in brain and skin were consistently lower than in tumour by
a factor of 10 or more. Although either
CuTCPH or
CuTCPBr can be labelled with (64)Cu for imaging by positron emission tomography (PET),
CuTCPBr can also be labelled by (76)Br, another PET-imageable nuclide.