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Background. Many neurotransmitter receptors are coupled to GTP-binding proteins and exist in high and low affinity states. After the endogenous transmitter binds to the receptor, the G-protein dissociates, the receptors transitions to low affinity state, and is often internalized. Most PET receptor radioligands are antagonists – i.e., block the actions of the transmitter) and show equal affinity to both states of the receptor. We developed a 11C-labled agonist for the dopamine D2 receptor. It should label only the high affinity state and be more sensitive to displacement by endogenously released dopamine. As predicted. in this study in monkeys, we found that the agonist radioligand (MNPA) showed greater displacement than the antagonist radioligand (raclopride). We plan to extend these studies to human subjects in collaboration with the Karolinska Institutet, Stockholm, Sweden.
Legend. Parametric images of [11C]raclopride and [11C]MNPA binding potential (BP) estimated by MRTM2 at baseline and postamphetamine conditions. Images represent the same monkey for each dose of amphetamine.
Reference. N. Seneca, S.J. Finnema, B. Gulyas, H.V. Wikstrom, L. Farde, C. Halldin, and R.B. Innis. Effect of amphetamine on dopamine D2 receptor binding in nonhuman primate brain: A comparison of the agonist ligand [11C]MNPA and the antagonist radioligand [11C]raclopride. Synapse. 59: 260-269, 2006.
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