Gallium-Labeled PET Radiopharmaceuticals in Cardiovascular Disease

Abstract

Gallium-labeled positron emission tomography (PET) probes targeting activated fibroblasts or somatostatin receptor expression are frequently used for varying applications in oncology. With the widespread availability of ⁶⁸Ge/⁶⁸Ga generators and cold kits, ⁶⁸Ga tracers have become a main tool in molecular imaging. These tracers, such as [⁶⁸Ga]Ga-DOTA-TATE, [⁶⁸Ga]Ga-FAPI, and [⁶⁸Ga]Ga-pentixafor, allow targeted imaging of the key pathological processes, including inflammation, fibrosis, and necrosis. This review highlights their potential in conditions like myocardial infarction, cardiac sarcoidosis, myocarditis, and other cardiomyopathies. Clinical and preclinical studies underscore their utility in visualizing active disease processes, predicting outcomes, and guiding therapeutic strategies. However, challenges remain, including the need for standardization, larger clinical trials, and integration into routine practice. These advancements position ⁶⁸Ga-based PET as a promising modality for enhancing diagnostic precision and personalized treatment in cardiovascular disease.

Keywords: CXCR4; DOTA; FAPI; cardiovascular; gallium-labeled radiopharmaceuticals; myocardial infarction; myocarditis; sarcoidosis.

Figure 1

Schematic representation of gallium-68-labeled radiopharmaceuticals and their targets in the context of cardiovascular diseases. [⁶⁸Ga]Ga-DOTATATE and [⁶⁸Ga]Ga-DOTATOC accumulates in macrophages and inflammatory cells via endocytosis after binding to the somatostatin receptor type 2 (SSTR2). Molecular imaging of vascular inflammation can also be monitored by targeting C-X-C chemokine receptor type 4 (CXCR4) using [⁶⁸ Ga]Ga-pentixafor. Cardiac remodeling following myocardial infarction implicates activated myofibroblasts that overexpress fibroblast activation protein (FAP).

Figure 2

Example of calcifying myocarditis under Revlimid on [⁶⁸Ga]-GaDOTATOC PET/CT ((a–c): short-axis slices, (d–i): long-axis slices). A 66-year-old patient showing increased left myocardial uptake, particularly in the infero-latero-basal region, adjacent to subepicardial calcifications (myocardial/blood SUVmax ratio of 2.75). CMR was inconclusive due to the extent of calcifications.