UPTAKE AND RETENTION OF NITROIMIDAZOLE-CARBORANES DESIGNED FOR BORON NEUTRON-CAPTURE THERAPY IN EXPERIMENTAL MURINE TUMORS - DETECTION BY B-11 MAGNETIC-RESONANCE SPECTROSCOPY

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 B-11 magnetic resonance spectroscopy. The comp ounds were injected i.p. at 0.8mmol/kg into mice bearing either the SC CVII/Ha squamous cell carcinoma or KHT sarcoma implanted intradermally on the mouse back. Boron from a polyether-isoxazole linked nitroimida zole-carborane (compound 1) was detectable in both SCCVII/Ha and KHT t umours at 3 and 7 h after injection. The signal from the liver at thes e times was greater than that from the tumour but only a weak signal w as 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 d isappeared by 24 h. Boron from a polyether-carbamate linked nitroimida zole-carborane (compound 2) was also detectable in both tumours at all times tested, and again was present in the liver. In addition, the B- 11 signal was detectable from the mouse brain, at early times, but was undetectable at 24 h. These preliminary data indicate that nitroimida zole-carboranes are taken up and retained in experimental murine tumou rs in sufficient amounts to be detectable by in vivo B MRS and further that at 24 h after treatment there is differential retention between rumours and the brain.