Beyond perfusion: a review of peptide radiopharmaceuticals for cardiovascular imaging

Cardiology is continually evolving towards increased personalization with targeted diagnostics and therapeutics. Peptide-based radiopharmaceuticals have emerged as a valuable tool for noninvasive, receptor-specific imaging, addressing limitations of traditional perfusion-based radiotracers like [¹⁵O]H₂O, [¹³N]NH₃, [⁸²Rb]RbCl and [99mTc]Tc-Sestamibi, which lack molecular specificity. While these conventional tracers provide crucial insights into myocardial perfusion and ventricular function, receptor-targeted imaging can illuminate the molecular mechanisms underlying cardiovascular diseases. This, in turn, offers novel insights into disease progression, enhanced diagnostic accuracy, and a tool for companion diagnostics of molecularly targeted therapeutics. Beyond receptor-mediated targeting, recent advances in cell-penetrating peptides (CPPs), such as the development of the cardiac targeting peptide (CTP), offer new opportunities for the enhanced delivery of a therapeutic payload to the injured heart. Their biodistribution can be effectively monitored using radiolabeled analogs. This review explores the role of peptide-based radiopharmaceuticals in nuclear cardiology, highlighting their applications in receptor-mediated imaging and briefly discussing non-receptor-specific CPPs. Select examples illustrate how these innovations are advancing molecular characterization of cardiovascular diseases such as fibrosis, cardiac amyloidosis, atherosclerosis, and more, reshaping the nuclear cardiology landscape.