IODINE-123-5-IODO-6-NITROQUIPAZINE - SPECT RADIOTRACER TO IMAGE THE SEROTONIN TRANSPORTER

Because serotonergic function has been implicated in the pathophysiolo gy of a number of diseases of the nervous system, efforts to image thi s system in vivo have received considerable recent attention. Promisin g preliminary results with the tracer 5-iodo-6-nitroquipazine (INQUIP) have prompted us to perform further studies designed to validate the use of the tracer as an in vivo ligand for the serotonin transporter. Methods: We studied six adult macaca mulatta in eight experiments whic h involved SPECT imaging at 17 to 24 hr post-tracer injection, includi ng three experiments with coinjection of the I-123- and I-125-radiolab eled tracer for direct comparison of autoradiography and SPECT, and th ree experiments in which animals were lesioned with the serotonergic n eurotoxin (+/-)3,4-methylenedioxymethamphetamine (MDMA). In addition, we evaluated the metabolism of the tracer in the brain and periphery. Results: SPECT images obtained at 17 and 24 hr reflected the known pat tern of distribution of serotonin transporters and also showed close c orrespondence to the autoradiograms. Ratios of binding in the brainste m to binding in the cerebellum were close lo 3 at 17 hr. Autoradiogram s from an MDMA-treaied animal showed up to 95% reductions of binding, while the SPECT data showed smaller reductions. Virtually all of the t racer in the brain stem was in the form of unmetabolized parent compou nd, but plasma showed rapid peripheral metabolism of the tracer. Concl usion: These results demonstrate that INQUIP SPECT images are sensitiv e measures of in vivo binding to the serotonin transporter, and suppor t the further development of the tracer as a method for the in vivo st udy of serotonergic neurons in humans.