Radiosynthesis of [N-13]dantrolene, a positron emission tomography probe for breast cancer resistant protein, using no-carrier-added [N-13]ammonia

Dantrolene (1) is a substrate for breast cancer resistant protein, which is widely distributed in the blood-brain-barrier, intestine, gall bladder, and liver. PET study with 1 labeled with a positron emitter can be used to visualize BCRP and to elucidate the effect of BCRP on the pharmacokinetics of drugs. The objective of this study was to label 1 using nitrogen-13 (N-13, a positron emitter; half-life: 9.9 min). Using no-carrier-added [N-13]NH3 as the labeling agent, we synthesized [N-13] dantrolene ([N-13] 1) for the first time. The reaction of carbomyl chloride 2b with [N-13]NH3 gave an unsymmetrical urea [N-13]3, followed by cyclization of [N-13]3 to afford [N-13]1. Due to its instability, 2b was prepared in situ by treating amine 5 with triphosgene in a ratio of 4 to 1 and used for subsequent [N-13] ammonolysis without purification. (C) 2011 Elsevier Ltd. All rights reserved.