Mol Pharm. 2026 May 18. doi: 10.1021/acs.molpharmaceut.6c00266. Online ahead of print.
ABSTRACT
C-C chemokine receptor type 2 (CCR2)+ monocytes and macrophages play a critical role in cardiovascular inflammation. In this study, we developed an 18F-labeled CCR2-targeted positron emission tomography (PET) radiotracer, [18F]AlF-NOTA-PEG-ECL1i, for the noninvasive imaging of cardiac inflammation. Using a one-step [18F]AlF-NOTA chelation strategy, [18F]AlF-NOTA-PEG-ECL1i was efficiently synthesized from [18F]fluoride and exhibited excellent radiochemical purity (>98%), high in vitro and in vivo stability, and a low lipid-water partition coefficient (log P = -4.52 ± 0.19). Biodistribution studies demonstrated predominant renal clearance and low nonspecific background uptake. In mice and swine models of cardiac ischemia-reperfusion (I/R) injury, radiotracer uptake increased in the injured myocardium. This observation was further validated by myocardial perfusion imaging, triphenyltetrazolium chloride staining, and ex vivo autoradiography. Furthermore, longitudinal PET/computed tomography (CT) from baseline to 24 days after I/R injury demonstrated that [18F]AlF-NOTA-PEG-ECL1i uptake in the injured myocardium was consistent with time-dependent changes in CCR2+ cell density. These results support [18F]AlF-NOTA-PEG-ECL1i as a promising CCR2-targeted PET radiotracer for imaging cardiac inflammation.
PMID:42150152 | DOI:10.1021/acs.molpharmaceut.6c00266