title: Enhancement of the radiation response of EMT-6 tumours by a copper octabromotetracarboranylphenylporphyrin.
abstract: OBJECTIVE
  The carborane-containing porphyrin, copper (II) 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(3-[1,2-dicarba-closo-dodecaboranyl]methoxyphenyl)-porphyrin (CuTCPBr), was investigated as a potential radiation enhancing agent for X-ray radiotherapy (XRT) in a subcutaneously implanted EMT-6 murine carcinoma.
  
  
  METHODS
  The biodistribution and toxicological profile of this porphyrin has been shown to be favourable for another bimodal radiotherapy technique, boron neutron-capture therapy. For the XRT studies, CuTCPBr was formulated in either 9% Cremophor (BASF Corporation, Ludwigschafen, Germany) EL and 18% propylene glycol (9% CRM) or a revised formulation comprising 1% Cremophor ELP, 2% Tween 80 (JT Baker, Mansfield, MA), 5% ethanol and 2.2% PEG 400 (CTEP formulation), which would be more clinically acceptable than the original 9% CRM formulation. Using the 9% CRM formulation of CuTCPBr, doses of 100, 210 or 400 mg kg(-1) of body weight were used in combination with single doses of 25-35 Gy 100 kVp X-rays.
  
  
  RESULTS
  While doses of 100 mg kg(-1) and 210 mg kg(-1) did not result in any significant enhancement of tumour response, the 400 mg kg(-1) dose did. A dose modification factor of 1.20±0.10 was obtained based on the comparison of doses that produced a 50% local tumour control probability. With the CTEP formulation of CuTCPBr, doses of 83 and 170 mg kg(-1) produced significant radiation enhancement, with dose modification factors based on the TCP(50) of 1.29±0.15 and 1.84±0.24, respectively.
  
  
  CONCLUSIONS
  CuTCPBr significantly enhanced the efficacy of XRT in the treatment of EMT-6 carcinomas in mice. The CTEP formulation showed a marked improvement, with over 9% CRM being associated with higher dose modification factors. Moreover, the radiation response in the skin was not enhanced.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. Miura@bnl.gov
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: G M
authors.initials: GM
authors.lastname: Morris
authors.forename: J W
authors.initials: JW
authors.lastname: Hopewell
authors.forename: P L
authors.initials: PL
authors.lastname: Micca
authors.forename: M S
authors.initials: MS
authors.lastname: Makar
authors.forename: M M
authors.initials: MM
authors.lastname: Nawrocky
authors.forename: M W
authors.initials: MW
authors.lastname: Renner
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D005260:Female; D008665:Metalloporphyrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000532:radiotherapy*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012867:Skin / Q000528:radiation effects; D014018:Tissue Distribution
chemical_list: D008665:Metalloporphyrins; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C572312:copper (II) 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(3-(1,2-dicarba-closo-dodecaboranyl)methoxyphenyl)porphyrin
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