Dopamine D3 receptor binding of 18 F‐fallypride: Evaluation using in vitro and in vivo PET imaging studies

Identification of dopamine D3 receptors (D3R) in vivo is important to understand several brain functions related to addiction. The goal of this work was to identify D3R binding of the dopamine D2 receptor (D2R)/D3R imaging agent, 18 F‐fallypride. Brain slices from male Sprague‐Dawley rats ( n  = 6) and New Zealand White rabbits ( n  = 6) were incubated with 18 F‐fallypride and D3R selective agonist ( R )‐7‐OH‐DPAT (98‐fold D3R selective). Rat slices were also treated with BP 897 (68‐fold D3R selective partial agonist) and NGB 2904 (56‐fold D3R selective antagonist). In vivo rat studies ( n  = 6) were done on Inveon PET using 18‐37 MBq 18 F‐fallypride and drug‐induced displacement by ( R )‐7‐OH‐DPAT, BP 897 and NGB 2904. PET/CT imaging of wild type (WT, n  = 2) and D2R knock‐out (KO, n  = 2) mice were carried out with 18 F‐fallypride. ( R )‐7‐OH‐DPAT displaced binding of 18 F‐fallypride, both in vitro and in vivo . In vitro , at 10 nM ( R )‐7‐OH‐DPAT, 18 F‐fallypride binding in the rat ventral striatum (VST) and dorsal striatum (DST) and rabbit nucleus accumbens were reduced by ∼10–15%. At 10 μM ( R )‐7‐OH‐DPAT all regions in rat and rabbit were reduced by ≥85%. In vivo reductions for DST and VST before and after ( R )‐7‐OH‐DPAT were: low‐dose (0.015 mg kg −1 ) DST −22%, VST −29%; high‐dose (1.88 mg kg −1 ) DST −58%, VST −77%, suggesting D 3 R/D 2 R displacement. BP 897 and NGB 2904 competed with 18 F‐fallypride in vitro , but unlike BP 897, NGB 2904 did not displace 18 F‐fallypride in vivo . The D2R KO mice lacked 18 F‐fallypride binding in the DST. In summary, our findings suggest that up to 20% of 18 F‐fallypride may be bound to D3R sites in vivo . Synapse 69:577–591, 2015 . © 2015 Wiley Periodicals, Inc.