Synthesis of a nickel tetracarboranylphenylporphyrin for boron neutron-capture therapy: biodistribution and toxicity in tumor-bearing mice

Int J Cancer. 1996 Sep 27;68(1):114-9. doi: 10.1002/(SICI)1097-0215(19960927)68:1<114::AID-IJC20>3.0.CO;2-A.

Abstract

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 microg NiTCP/gram body weight (gbw) (54 microg 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 microg 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Blood Urea Nitrogen
  • Boron / analysis
  • Boron / blood
  • Boron Neutron Capture Therapy*
  • Brain Chemistry
  • Female
  • Kinetics
  • Mammary Neoplasms, Experimental / chemistry
  • Mammary Neoplasms, Experimental / radiotherapy*
  • Metalloporphyrins / chemical synthesis
  • Metalloporphyrins / pharmacokinetics*
  • Metalloporphyrins / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Tissue Distribution

Substances

  • Metalloporphyrins
  • nickel-2,3,7,8,12,13,17,18-octaacetic acid-5,10,15,20-tetra-(3-carboranylmethoxyphenyl)porphyrin octamethyl ester
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Boron