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.

METHOD:

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.

CONCLUSION:

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: M Miura, G M Morris, J W Hopewell, P L Micca, M S Makar, M M Nawrocky, M W Renner
• Journal: The British journal of radiology (Br J Radiol) Vol. 85 Issue 1012 Pg. 443-50 (Apr 2012) ISSN: 1748-880X [Electronic] England
• PMID: 22096223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Metalloporphyrins
• Porphyrins
• Radiation-Sensitizing Agents
• copper (II) 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(3-(1,2-dicarba-closo-dodecaboranyl)methoxyphenyl)porphyrin

Topics

• Animals
• Dose-Response Relationship, Drug
• Electrochemistry
• Female
• Metalloporphyrins (pharmacokinetics, pharmacology)
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental (radiotherapy)
• Porphyrins (pharmacokinetics, pharmacology)
• Radiation-Sensitizing Agents (pharmacology)
• Skin (radiation effects)
• Tissue Distribution