PET studies of binding competition between endogenous dopamine and the D1 radiotracer [11C]NNC 756
✍ Scribed by Anissa Abi-Dargham; Norman Simpson; Lawrence Kegeles; Ramin Parsey; Dah-Ren Hwang; Satish Anjilvel; Yolanda Zea-Ponce; Ilise Lombardo; Ronald Van Heertum; John J. Mann; Christian Foged; Christer Halldin; Marc Laruelle
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 243 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
NNC 756 ((ϩ)-8-chloro-5-(2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3methyl-2,3,4,5-tetrahydro-1H-3-benzazepine) is a new high affinity dopamine (DA) D 1 receptor antagonist. Labeled with C-11, it has been used as a PET radiotracer to visualize D 1 receptors both in striatal and extrastriatal areas, such as the prefrontal cortex. The goal of this study was to evaluate several methods for derivation of D 1 receptor binding potential (BP) with [ 11 C]NNC 756 in baboons, and to use these methods to assess the vulnerability of [ 11 C]NNC 756 binding to competition by endogenous DA. A threecompartment model provided a good fit to PET data acquired following a single bolus injection. BP values obtained with this analysis were in good agreement with values derived from in vitro studies. BP values measured following injection of the potent DA releaser amphetamine (1 mg/kg, n ϭ 2) were similar to values measured under control conditions. Kinetic parameters derived from single bolus experiments were used to design a bolus plus continuous infusion administration protocol aimed at achieving a state of sustained binding equilibrium. Injection of amphetamine during sustained equilibrium did not affect [ 11 C]NNC 756 binding. Similar results were observed with another D 1 radiotracer, [ 11 C]SCH 23390. Doses of amphetamine used in this study are known to reduce by 20-40% the binding potential of several D 2 receptors radiotracers. Therefore, the absence of displacement of [ 11 C]NNC 756 by an endogenous DA surge may indicate important differences between D 1 and D 2 receptors in vivo, such as differences in proportion of high affinity states not occupied by DA at baseline. These findings may also imply that a simple binding competition model is inadequate to account for the effects of manipulation of endogenous DA levels on the in vivo binding of radiolabeled antagonists.