The biodistributions of carborane-containing
copper porphyrins, CuTCP and
CuTCPH, have been studied previously in mice bearing subcutaneously implanted mammary
carcinomas. We now report biodistributions of those
porphyrins in Fischer 344 rats bearing intracranial and/or multiple subcutaneous isogeneic 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 (microg/g) 3 days after the end of infusion were: 64 in subcutaneous
tumor, 13 in intracranial
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 (microg 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 biodistribution was also studied in xenografts of the human
malignant gliomas U87 and U373, and of the murine EMT-6 mammary
carcinoma and the rat 9LGS, each grown subcutaneously in mice with
severe combined immunodeficiency (SCIDs). In SCIDs, median
boron concentrations (microg/g) 2 days after the last s.c. injection 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 intracerebral human
glioblastoma multiforme (GBM) microscopically,
CuTCPH could prove useful as a
boron carrier for
boron neutron-capture therapy (BNCT) of GBM and of other human
malignant gliomas.