TY - JOUR T1 - PET Imaging Evaluation of Four σ<sub>1</sub> Radiotracers in Nonhuman Primates JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 982 LP - 988 DO - 10.2967/jnumed.116.188052 VL - 58 IS - 6 AU - Evan Baum AU - Zhengxin Cai AU - Frederic Bois AU - Daniel Holden AU - Shu-fei Lin AU - Teresa Lara-Jaime AU - Michael Kapinos AU - Yuanyuan Chen AU - Winnie Deuther-Conrad AU - Steffen Fischer AU - Sladjana Dukic-Stefanovic AU - Paul Bunse AU - Bernhard Wünsch AU - Peter Brust AU - Hongmei Jia AU - Yiyun Huang Y1 - 2017/06/01 UR - http://jnm.snmjournals.org/content/58/6/982.abstract N2 - The σ1 receptors (S1Rs) are implicated in a variety of diseases including Alzheimer disease and cancer. Previous PET S1R radiotracers are characterized by slow kinetics or off-target binding that impedes their use in humans. Here, we report the first PET imaging evaluation in rhesus monkeys of 4 18F-labeled spirocyclic piperidine-based PET radiotracers (18F-1 to 18F-4). Methods: Baseline scans for the 4 radiotracers were obtained on an adult male rhesus monkey. Blocking scans were obtained with the S1R-selective agonist SA4503 to assess binding specificity of 18F-2 and 18F-4. Arterial input functions were measured, and binding parameters were determined with kinetic modeling analysis. Results: In the rhesus brain, all 4 radiotracers showed high and fast uptake. Tissue activity washout was rapid for 18F-2 and 18F-4, and much slower for 18F-1 and 18F-3, in line with their respective in vitro S1R-binding affinities. Both the 1-tissue-compartment and multilinear analysis-1 kinetic models provided good fits of time–activity curves and reliable estimates of distribution volume. Regional distribution volume values were highest in the cingulate cortex and lowest in the thalamus for all radiotracers. 18F-4 showed greater differential uptake across brain regions and 3-fold-higher binding potential than 18F-2. SA4503 at the dose of 0.5 mg/kg blocked approximately 85% (18F-2) and 95% (18F-4) of radiotracer binding. Conclusion: Tracers 18F-2 and 18F-4 displayed high brain uptake and fast tissue kinetics, with 18F-4 having higher specific binding signals than 18F-2 in the same monkey. Taken together, these data indicate that both 18F-2 and 18F-4 possess the requisite kinetic and imaging properties as viable PET tracers for imaging S1R in the human brain. ER -