Development, synthesis, and ⁶⁸Ga-Labeling of a Lipophilic complexing agent for atherosclerosis PET imaging

Area of Science:

• Nuclear Medicine
• Cardiovascular Imaging
• Radiopharmaceutical Chemistry

Background:

• Cardiovascular disease, particularly atherosclerosis, is a major global health concern.
• Atherosclerosis involves lipid and inflammatory cell accumulation in vascular walls, forming plaques.
• Current imaging methods for atherosclerosis have limitations in sensitivity and specificity.

Purpose of the Study:

• To synthesize and evaluate a novel ⁶⁸Ga-based radiotracer for PET imaging of atherosclerosis.
• To assess the efficacy of ⁶⁸Ga-PCTA-DSPE, incorporated into High-Density Lipoprotein (HDL) particles, for plaque visualization.

Main Methods:

• Synthesis of a ⁶⁸Ga³⁺ chelator (PCTA) coupled to a phospholipid biovector (1,2-distearoyl-sn-glycero-3-phosphoethanolamine, DSPE).
• Incorporation of the ⁶⁸Ga-PCTA-DSPE conjugate into HDL particles.
• Comparison of ⁶⁸Ga-PCTA-DSPE-HDL with ¹⁸F-FDG as a PET imaging agent in mouse models and human carotid endarterectomy samples.

Main Results:

• The novel ⁶⁸Ga-PCTA-DSPE agent demonstrated significant accumulation in atherosclerotic aortas of mice.
• Enhanced uptake was also observed in human carotid artery samples from endarterectomy procedures.
• ⁶⁸Ga-PCTA-DSPE-HDL showed comparable or superior performance to ¹⁸F-FDG for plaque visualization.

Conclusions:

• ⁶⁸Ga-PCTA-DSPE-HDL is a promising new radiotracer for PET imaging of atherosclerosis.
• This agent facilitates the visualization of atherosclerotic plaques in preclinical and clinical settings.
• Further research is warranted to explore its full clinical potential in cardiovascular disease management.