TY - JOUR T1 - Evaluation of dopamine D<sub>3</sub> receptor binding of <sup>18</sup>F-fallypride JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1762 LP - 1762 VL - 51 IS - supplement 2 AU - Taleen Jerjian AU - Cristian Constantinescu AU - Evgueni Sevrioukov AU - Jogesh Mukherjee Y1 - 2010/05/01 UR - http://jnm.snmjournals.org/content/51/supplement_2/1762.abstract N2 - 1762 Objectives Identification of dopamine D3 receptors in vivo is important to understand several brain functions. Fallypride and other substituted benzamides (raclopride, IBZM, FLB457) are known to bind to both D2 and D3 receptors. Using (R)-7-OH-DPAT (DPAT), a selective D3 agent (Ki=0.57 nM) over D2 (Ki=56nM), we have measured degree of displacement of 18F-fallypride in vitro and in vivo. Methods Brain tissue was obtained from male Sprague-Dawley rats and New Zealand White rabbits in sections (10 μm thick) including striata, cortex and cerebellum. Sections were preincubated at rt for 10 min in Tris-HCl buffer (pH 7.4). Incubation was with 2-3 μCi/cc of 18F-fallypride (&gt;2 Ci/mmol) at 37oC for 1 hr along with 0.1nM to 10 μM (R)-7-OH-DPAT. Post incubation, sections were washed twice for 3 min in cold buffer, submerged quickly in cold distilled water, dried, exposed to phosphor films and quantified. Rat (isoflurane anesthesia) in vivo studies were done on Inveon MicroPET with (R)-7-OH-DPAT at doses of 0.4 and 1.9 mg/kg IV 90 min postinjection of ~1 mCi 18F-fallypride. Results (R)-7-OH-DPAT displaced binding of 18F-fallypride, both in vitro and in vivo. In vitro at 10nM (R)-7-OH-DPAT, rat ventral striatum (VST) and dorsal striatum (DST) were reduced by ~10% (D3 displacement). Rabbit sagittal sections were similarly reduced (caudate &amp; putamen) but nucleus accumbens was reduced by ~15%. However at 10μM (R)-7-OH-DPAT all regions in rat and rabbit were reduced by ≥85% (D2 displacement). In vivo binding was computed as percent reduction of cerebellar ratio for dorsal striatum (DST) and ventral striatum (VST) before and after (R)-7-OH-DPAT: low-dose (0.4mg/kg) DST -48%, VST -56%; high-dose (1.9 mg/kg) DST -64%, VST -82%, suggesting D3/D2 displacement. Conclusions In vitro data suggests that approximately 10-15% of 18F-fallypride may be bound to D3 receptor sites. In vivo data shows displacement from both DST and VST by (R)-7-OH-DPAT with some selectivity for the latter. Lower doses of (R)-7-OH-DPAT are planned to further discriminate competition at VST from DST. Research Support NIH EB00611 ER -