Clinical Research on 68Ga-FAPI PET/CMR in Cardiovascular Diseases

Cardiovascular diseases (CVDs) are among the leading causes of death and disability worldwide. According to statistics from the World Health Organization (WHO), over 17 million people die from CVDs each year, accounting for 31% of global mortality\[1\]. In China, the incidence and mortality rates of CVDs continue to rise alarmingly. The China Cardiovascular Health and Diseases Report indicates that approximately 300 million Chinese suffer from CVDs, with annual CVD-related deaths exceeding 4 million - representing over 40% of the country's total deaths\[2\]. These concerning trends highlight CVDs as a major public health crisis demanding urgent attention.

Recent advances in molecular imaging have opened new avenues for CVD diagnosis and management. Fibroblast activation protein (FAP), a type II transmembrane serine protease, shows minimal expression in normal tissues but becomes markedly upregulated in various pathological conditions including malignant tumors, inflammatory diseases, and fibrotic processes\[3,4\]. Of particular significance is its role in myocardial fibrosis - a key pathological mechanism underlying many CVDs\[5\]. Current diagnostic methods for myocardial fibrosis remain limited, with histopathology being invasive and conventional imaging techniques like echocardiography and cardiac MR (CMR) only detecting late-stage changes. The emergence of radiolabeled FAP inhibitors (FAPIs) has enabled non-invasive visualization of early myocardial fibrosis, offering unprecedented opportunities for dynamic monitoring of disease progression and treatment response.

The clinical potential of FAPI-based imaging in CVDs is increasingly recognized. Although still in the exploratory phase, studies have consistently demonstrated FAPI uptake in various CVD animal models and human patients, confirming the activation of cardiac fibroblasts and FAP expression across different disease states. This technology provides three key advantages: first, it allows in vivo visualization of fibroblast activity at molecular levels; second, it enables early detection of fibrotic changes before structural damage occurs; third, when combined with other imaging modalities, it permits comprehensive assessment of disease progression. These capabilities make FAPI imaging a powerful tool for identifying candidates for anti-fibrotic therapy and monitoring treatment efficacy.

Integrated PET/MR technology represents another major breakthrough in cardiac imaging. By combining the superior soft-tissue resolution of MR with PET's molecular sensitivity, simultaneous PET/CMR systems provide unparalleled insights into cardiac structure and function\[6\]. This hybrid approach integrates anatomical details from CMR (including late gadolinium enhancement patterns) with metabolic information from PET, delivering more comprehensive data than either modality alone. Importantly, PET/CMR achieves this without additional radiation exposure from CT components, making it particularly suitable for longitudinal studies. While clinical applications in CVDs remain investigational, PET/CMR holds tremendous promise for advancing our understanding of disease mechanisms and enabling personalized treatment strategies.

This research project aims to harness these technological advancements for improved CVD management. By implementing 68Ga-FAPI PET/CMR multi-modal imaging, we seek to achieve precise quantification of myocardial fibrosis and comprehensive evaluation of cardiac function in a single examination. The synergistic combination of 68Ga-FAPI's molecular targeting capability with CMR's structural and functional assessment offers several clinical benefits: it streamlines diagnostic workflows, enhances accuracy, facilitates timely intervention, and ultimately may improve patient outcomes. Through this innovative approach, we hope to establish a new paradigm in CVD care that combines cutting-edge imaging technology with personalized medicine principles, thereby addressing the growing burden of cardiovascular diseases more effectively.