Uptake and retention of nitroimidazole-carboranes designed for boron neutron capture therapy in experimental murine tumours: detection by 11B magnetic resonance spectroscopy.

Abstract

Two novel nitroimidazole-carboranes were examined for their uptake and retention in two experimental murine solid tumours and in some normal tissues, using in vivo 11B magnetic resonance spectroscopy. The compounds were injected i.p. at 0.8mmol/kg into mice bearing either the SCCVII/Ha squamous cell carcinoma or KHT sarcoma implanted intradermally on the mouse back. Boron from a polyether-isoxazole linked nitroimidazole-carborane (compound 1) was detectable in both SCCVII/Ha and KHT tumours at 3 and 7 h after injection. The signal from the liver at these times was greater than that from the tumour but only a weak signal was obtained from the brain. At 24 h after injection the tumour signal was still present, as was that from the liver, which appeared to have increased over that for the earlier times. Signal from the brain had disappeared by 24 h. Boron from a polyether-carbamate linked nitroimidazole-carborane (compound 2) was also detectable in both tumours at all times tested, and again was present in the liver. In addition, the 11B signal was detectable from the mouse brain, at early times, but was undetectable at 24 h. These preliminary data indicate that nitroimidazole-carboranes are taken up and retained in experimental murine tumours in sufficient amounts to be detectable by in vivo 11B MRS and further that at 24 h after treatment there is differential retention between tumours and the brain.