TY - JOUR T1 - <strong>Design and preclinical evaluation of [<sup>18</sup>F]CNY-05, a next generation of sigma-1 receptor (<em>ó</em><sub>1</sub>R) radiotracer for brain imaging of positron emission tomography (PET)</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 202 LP - 202 VL - 61 IS - supplement 1 AU - YU LAN AU - Ping Bai AU - Hao Wang AU - Changning Wang Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/202.abstract N2 - 202Introduction: Developing aromatic 18F-fluorinated labeled drug-like molecular is the most attractive and potential area of receptor-binding PET radiotracer due to the prevalence in pharmaceuticals and its metabolic stability. However, the deficiency of straight and efficient labeling method limited the progress and application in PET imaging. Herein we reported a next generation of aromatic 18F-labeled σ1R PET tracer achieved through an innovative aromatic 18F-deoxyfluorination and its preliminary evaluation. Methods: Firstly, radiosynthesis [18F]CNY-05 was conducted with the its corresponding phenol precursor and air stable Ru complex (CpRu(COD)Cl). Then preliminary in vivo imaging studies were performed in rodents to study the potential of [18F]CNY-05 to serve as a radiotracer for brain σ1R imaging. Male Balb/c mice were administered [18F]CNY-05 via intravenous bolus injection (100‒150 μCi per animal) and then followed a 60 minutes dynamic PET imaging and a 10 minutes computed tomography (CT) scanning. The biodistribution of [18F]CNY-05 in mice brain was also investigated, the data of different brain regions were acquired in the FUSION module in PMOD (PMOD 4.003, PMOD Technologies Ltd., Zurich, Switzerland), using the mouse (Ma-Benveniste-Mirrione) VOI atlas. Results: From the analysis of radioactive uptake in whole brain, [18F]CNY-05 could reached the maximum uptake of 10.2 %ID/cc of uptake in mice brain in first few minutes after injection and exhibited good brain clearance kinetic property during the scanning period. Pretreated unlabeled CNY-05 and classic σ1R drug haloperidol could significantly decreased the brain uptake of [18F]CNY-05, indicated the specific binding and metabolic stability in brain.(Figure 1) In regional brain analysis of [18F]CNY-05 showed difference in uptake cross regions, due to the different express of σ1R (Figure 2). In thalamus, cerebellum and hippocampus, the [18F]CNY-05 uptake were higher than other brain regions, similar to the distribution patterns reported previously. Conclusions: In summary, a next generation of 18F-labeled σ1R radiotracer, [18F]CNY-05 was successfully synthesized by using an Ru-mediated aromatic 18F-deoxyfluorination. In in vivo evaluation, [18F]CNY-05 exhibits great potential in rodent. Using [18F]CNY-05 as a PET probe could great benefit to quantify σ1R expression in various neurological disorders, and would also be valuable for evaluation of potential drugs in living subjects. Acknowledgements: Support for this work includes a pilot funding from the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital (Changning Wang, USA), National Natural Science Foundation of China (Grant No.81602946, Yu Lan) and Natural Science Foundation of Hubei Province of China (Grant No. 2016CFB258, Yu Lan). ER -