@article {Mach159, author = {Robert Mach and Zhude Tu and Jinbin Xu and Suwanna Vangveravong and Shihong Li and Jinda Fan and Lynne Jones and Joel Perlmutter and Mark Mintun}, title = {Differential distribution of dopamine D2 and D3 receptors in the Rhesus brain measured with PET}, volume = {51}, number = {supplement 2}, pages = {159--159}, year = {2010}, publisher = {Society of Nuclear Medicine}, abstract = {159 Objectives PET tracers for dopamine D2-like receptors display little selectivity for D2 and D3 receptors. Consequently, the differential distribution of D2 and D3 receptors in brain is poorly understood. Two highly selective imaging agents developed in our group, the D2-selective probe [11C]SV-III-130 (D2 = 0.22 nM; D3 = 13.1 nM) and the D3-selective probe [18F]LS-3134 (D3 = 0.17 nM; D2 = 27.7 nM) were used to image the regional distribution of these receptors. Methods [11C]SV-III-130 was synthesized in 60\% yield (EOB), SA 1 Ci/μmol, by alkylating the des-methyl precursor with [11C]methyl iodide. [18F]LS-3134 was synthesized by displacement of the mesylate precursor with [18F]fluoride to give the radiotracer in 50\% yield (EOB) and high SA (\>2,000 Ci/μmol). MicroPET studies were conducted in rhesus monkeys (n = 3) using either a 60 min ([11C]SV-III-130) or 120 min ([18F]LS-3134) dynamic acquisition. Studies with [18F]LS-3134 were conducted following lorazepam treatment to minimize competition with endogenous dopamine. Binding potentials (BP) relative to cerebellum were calculated using graphical analysis. Results [11C]SV-III-130 had high uptake in rhesus caudate and putamen with identical BP. [18F]LS-3134 had moderate uptake in rhesus caudate, putamen and thalamus. BP values of [18F]LS-3134 were lower than those of [11C]SV-III-130, indicating a lower density of D3 vs. D2 receptors in the caudate and putamen. BP values of [18F]LS-3134 in the caudate and thalamus were lower than that in the putamen. The differential uptake (Table) of [18F]LS-3134 vs. [11C]SV-III-130 indicates that D3 but not D2 is expressed in the thalamus. Conclusions These data suggest that [11C]SV-III-130 and [18F]LS-3134 can be used to image the differential distribution of D2 and D3 receptors in the CNS. Research Support Funded by DA16181, MH81281 and NS4805}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/51/supplement_2/159}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }