Use of ex vivo binding to measure the brain concentrations of putative radioligands

The development of radioligands capable of imaging brain receptors depends on, amongst other factors, the ability of such compounds to penetrate the blood-brain barrier. We describe an ex vivo binding technique for measuring the brain concentration of peripherally administered unlabeled compounds. This technique can be used early in the development of putative radioligands. The pharmacokinetics of brain penetration of three muscarinic antagonists are described: QNB, BrQNB and the 2-thienyl derivative of BrQNB and were found to compare favorably to previous studies using [³H]QNB. These studies demonstrate the effectiveness of ex vivo binding in assessing the brain concentration of peripherally administered unlabeled compounds.