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Synthesis of a nickel tetracarboranylphenylporphyrin for boron neutron‐capture therapy: Biodistribution and toxicity in tumor‐bearing mice
Author(s) -
Miura Michiko,
Micca Peggy L.,
Fisher Craig D.,
Heinrichs John C.,
Donaldson Jason A.,
Finkel Gerald C.,
Slatkin Daniel N.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960927)68:1<114::aid-ijc20>3.0.co;2-a
Subject(s) - biodistribution , toxicity , radiochemistry , boron , chemistry , nuclear medicine , body weight , acute toxicity , medicine , pharmacology , nuclear chemistry , biochemistry , in vitro , organic chemistry
Nickel‐2,3,7,8,12,13,17,18‐octaacetic acid‐5,10,15,20‐tetra‐[3‐carboranyl‐methoxyphenyl]‐porphyrin octamethylester (NiTCP) was given in a Cremophor EL, a polyethoxylated castor oil, and propylene glycol emulsion to BALB/c mice bearing transplanted s.c. KHJJ mammary carcinomas. A total dose of 244 μg NiTCP/gram body weight (gbw) (54 μg B/gbw) was given in 6 i.p. injections over a 32 hr period. Observations of behavior and changes in body weight and chemical and hematological blood tests indicated little or no toxicity from NiTCP over a period of 6–90 hr after injections. Boron concentrations near tumor margins were 160–180 μg B/g at 41–90 hr after the last injection. Tumor:normal brain boron concentration ratios reached approx. 10:1 and tumor:blood ratios reached approx. 250:1 after 4 days. There was no evidence of thrombocytopenia or other potentially important toxicities. Our findings place NiTCP among the leading candidates for pre‐clinical experiments aimed toward improvement upon the compounds being tested for boron neutron‐capture therapy of glioblastoma multiforme. © 1996 Wiley‐Liss, Inc.