RT Journal Article SR Electronic T1 Development of New CCR2 PET Tracer Imaging Atherosclerosis JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 3341 OP 3341 VO 63 IS supplement 2 A1 Zhang, Xiuli A1 Heo, Gyu Seong A1 Zhang, Xiaohui A1 Detering, Lisa A1 Sultan, Debbie A1 Luehmann, Hannah A1 Lou, Lanlan A1 Reichert, David A1 Liu, Yongjian YR 2022 UL http://jnm.snmjournals.org/content/63/supplement_2/3341.abstract AB 3341 Introduction: CC chemokine receptor type 2 (CCR2) is a promising biomarker for the diagnosis and treatment of inflammation and tumor. A diagnostic tool capable of assessing CCR2 abundance while predicting and monitoring treatment response will be invaluable. Therefore, Based on CCR2 targeting PET radiotracer (64Cu-DOTA-ECL1i), we developed a new tracer (64Cu-DOTA-DR-1) through molecular modeling and evaluated its specificity in vitro, and sensitivity in pre-clinical mouse models. Methods: DR-1 peptide was developed by docking method. DOTA-DR-1 peptide was synthesized using solid phase Fmoc synthesis and conjugated to DOTA. The DOTA-DR-1 conjugate (1.0 μg) was radiolabeled with 37 MBq of 64Cu in 0.1M NH4OAc buffer (pH 5.5) at 45oC for 40 min. THP-1 cells were used for cell binding and IC50 testing in vitro. PET/CT imaging using CCR2 targeted 64Cu-DOTA-DR-1 was performed at 1 h post injection in apolipoprotein E-deficient (Apoe-/-) mouse (12 weeks on high fat diet (HFD) model and compared to wild type mice. Results: The binding affinity of DR-1 peptide to CCR2 receptor was -89.5 kJ·mol-1, while the binding affinity of ECL1i was -72.3 kJ·mol-1 calculated by docking method. The radiolabeling specific activity was measured as 4.89×1010MBq·mol-1. In THP-1 cells, the IC50 of 64Cu-DOTA-DR-1 was determined as 3.1×10-8 M. Biodistribution in wild type mice showed low blood retention and rapid renal clearance. In Apoe-/-mice at 12 weeks post HFD, 64Cu-DOTA-DR-1 was clearly visualized at atherosclerosis lesions while little PET signal was detected in the wild type control mice. Conclusions: This study demonstrated the success of molecular modeling in radiotracer development for CCR2 imaging. 64Cu-DOTA-DR-1 is a promising tracer for CCR2 PET imaging. The sensitive and specific detection of CCR2 warrants its further investigation of macrophages in other inflammatory diseases with PET/CT.