title: Biodistribution of copper carboranyltetraphenylporphyrins in rodents bearing an isogeneic or human neoplasm.
abstract: 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.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. miura@bnl.gov
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: D D
authors.initials: DD
authors.lastname: Joel
authors.forename: H M
authors.initials: HM
authors.lastname: Smilowitz
authors.forename: M M
authors.initials: MM
authors.lastname: Nawrocky
authors.forename: P L
authors.initials: PL
authors.lastname: Micca
authors.forename: D A
authors.initials: DA
authors.lastname: Hoch
authors.forename: J A
authors.initials: JA
authors.lastname: Coderre
authors.forename: D N
authors.initials: DN
authors.lastname: Slatkin
mesh_terms: D000818:Animals; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D003301:Copper Radioisotopes / Q000493:pharmacokinetics*; D005260:Female; D018316:Gliosarcoma / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000532:radiotherapy; D008665:Metalloporphyrins / Q000493:pharmacokinetics*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D003301:Copper Radioisotopes; D008665:Metalloporphyrins; C063213:5,10,15,20-tetrakis(4-carboxyphenyl)porphinatocopper(II)