Biodistribution of copper carboranyltetraphenylporphyrins in rodents bearing an isogeneic or human neoplasm

The biodistributions of carborane-containing copper porphyrins, CuTCP and C uTCPH, have been studied previously in mice bearing subcutaneously implante d mammary carcinomas. We now report biodistributions of those porphyrins in Fischer 344 rats bearing intracranial and/or multiple subcutaneous isogene ic 9L gliosarcomas (9LGS). The porphyrin was given either by i.v. infusion or by multiple i.p. injections. When 190 mg CuTCPH/kg body weight was given to the rats by i.v. infusion, median tissue boron concentrations (mug/g) 3 days after the end of infusion were: 64 in subcutaneous tumor, 13 in intra cranial tumor, 1 in blood and 3 in brain. When 450 mg CuTCPH/kg body weight was given to the rats by serial i.p. injections, the median concentrations (mug B/g) 4 days after the last injection were: 117 in subcutaneous tumor, 50 in intracranial tumor, 4 in blood, and 4 in brain. CuTCPH biodistributi on was also studied in xenografts of the human malignant gliomas U87 and U3 73, and of the murine EMT-6 mammary carcinoma and the rat 9LGS, each grown subcutaneously in mice with severe combined immunodeficiency (SCIDs). In SC IDs, median boron concentrations (mug/g) 2 days after the last s.c. injecti on of a total of 190 mg CuTCPH/kg body weight were: 251 in U373, 33 in U87, <0.6 in blood and <0.5 in brain. Because there were such high boron levels in the U373, and because xenografted U373 is similar to spontaneous intrac erebral human glioblastoma multiforme (GBM) microscopically, CuTCPH could p rove useful as a boron carrier for boron neutron-capture therapy (BNCT) of GBM and of other human malignant gliomas.