Emerging Role of FAP-Targeted PET Imaging in Assessing Fibroblast Activation in Cardiovascular Disorders: A Review

Cardiovascular fibrosis is a dynamic process that involves fibroblast activation, extracellular matrix production, and myocardial remodeling. While it can damage the heart through an unregulated and progressive response, it is also an essential component of the body’s repair mechanisms. Fibroblast activation protein (FAP) targeted positron emission tomography (PET) has emerged as a molecular imaging approach for showing FAP expression in association with activated fibroblasts, potentially providing complementary information to established and contemporary imaging techniques. This narrative review examines the biological basis, tracer development and emerging cardiovascular applications of FAP-targeted PET, with emphasis on the clinical applications and limitations of available evidence. Relevant publications were found through a PubMed/MEDLINE search and selected according to their relevance to cardiovascular FAP-targeted imaging and potential clinical applications. Recent developments include gallium-68-labeled tracers such as 68Ga-FAPI-04, fluorine-18-labeled tracers such as 18F-FAPI-74, and high-affinity ligand platforms such as ONCOFAP. Current evidence consists of case reports, preclinical investigations, and mostly small exploratory clinical studies across many cardiovascular conditions. These studies report associations between cardiovascular FAP tracer uptake and measures of myocardial injury, remodeling and cardiac function, primarily in small exploratory cohorts. However, it is important to note that FAP expression reflects fibroblast activation and does not directly establish active collagen deposition, pathological fibrosis or tissue reversibility. Also, differences in tracer selection and imaging protocol, small study sizes and limited standardization restrict the ability to fully understand the clinical applications of existing findings. Cardiovascular FAP-targeted PET, although promising, remains investigational, and its clinical utility, prognostic value, and superiority over established imaging methods have not been fully demonstrated. More standardized, prospective studies are required to determine its exact role in cardiovascular disease assessment and management.