PT - JOURNAL ARTICLE AU - James, Michelle L. AU - Shen, Bin AU - Nielsen, Carsten H. AU - Behera, Deepak AU - Buckmaster, Christine L. AU - Mesangeau, Christophe AU - Zavaleta, Cristina AU - Vuppala, Pradeep K. AU - Jamalapuram, Seshulatha AU - Avery, Bonnie A. AU - Lyons, David M. AU - McCurdy, Christopher R. AU - Biswal, Sandip AU - Gambhir, Sanjiv S. AU - Chin, Frederick T. TI - Evaluation of σ-1 Receptor Radioligand <sup>18</sup>F-FTC-146 in Rats and Squirrel Monkeys Using PET AID - 10.2967/jnumed.113.120261 DP - 2014 Jan 01 TA - Journal of Nuclear Medicine PG - 147--153 VI - 55 IP - 1 4099 - http://jnm.snmjournals.org/content/55/1/147.short 4100 - http://jnm.snmjournals.org/content/55/1/147.full SO - J Nucl Med2014 Jan 01; 55 AB - The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer 18F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain information about the potential of 18F-FTC-146 for eventual clinical translation. Methods: The distribution and stability of 18F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of 18F-FTC-146 stability in monkey plasma and human serum. Results: Biodistribution studies showed that 18F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated 18F-FTC-146 accumulation in all rat brain regions by approximately 85% (P &lt; 0.001), suggesting radiotracer specificity for S1Rs. Similarly, PET/CT and autoradiography results demonstrated accumulation of 18F-FTC-146 in rat brain regions known to contain S1Rs and that this uptake could be blocked by BD1047 pretreatment. Ex vivo analysis of 18F-FTC-146 in the brain showed that only intact radiotracer was present at 15, 30, and 60 min, whereas rapid metabolism of residual 18F-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of 18F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism, whereas 18F-FTC-146 appeared to be stable in human serum. Finally, liver microsome studies revealed that 18F-FTC-146 has a longer half-life in human microsomes, compared with rodents. Conclusion: Together, these results indicate that 18F-FTC-146 is a promising tool for visualizing S1Rs in preclinical studies and that it has potential for mapping these sites in the human brain.