An ¹⁸F-labeled ECL1i-Based C-C Chemokine Receptor Type 2 Radiotracer for Cardiac Inflammation Imaging

Area of Science:

• Cardiovascular Research
• Nuclear Medicine
• Molecular Imaging

Background:

• C-C chemokine receptor type 2 (CCR2)+ monocytes and macrophages are key players in cardiovascular inflammation.
• Noninvasive imaging of cardiac inflammation is crucial for diagnosis and monitoring.

Purpose of the Study:

• To develop and evaluate a novel 18F-labeled PET radiotracer targeting CCR2 for noninvasive cardiac inflammation imaging.
• To assess the efficacy of [18F]AlF-NOTA-PEG2-ECL1i in preclinical models of cardiac injury.

Main Methods:

• Synthesis of [18F]AlF-NOTA-PEG2-ECL1i using a one-step [18F]AlF-NOTA chelation strategy.
• In vitro and in vivo stability, radiochemical purity, and lipophilicity assessments.
• Biodistribution studies and PET/CT imaging in mice and swine models of cardiac ischemia-reperfusion (I/R) injury.

Main Results:

• [18F]AlF-NOTA-PEG2-ECL1i demonstrated high radiochemical purity (>98%) and excellent stability.
• The tracer exhibited predominant renal clearance and low background uptake.
• Increased radiotracer uptake was observed in the injured myocardium of I/R models, correlating with CCR2+ cell density over time.

Conclusions:

• [18F]AlF-NOTA-PEG2-ECL1i is a promising CCR2-targeted PET radiotracer for noninvasive imaging of cardiac inflammation.
• The tracer's ability to track time-dependent changes in CCR2+ cells supports its potential clinical utility.