Application of 68Ga- and 177Lu-Labeled FAP Inhibitor in Evaluation and Treatment of Cardiac Fibrosis After Myocardial Infarction

⁶⁸Ga and ¹⁷⁷Lu-labeled fibroblast activation protein inhibitor (FAPI) have been introduced for the diagnosis and treatment of multiple malignant and non-malignant diseases. While several studies have examined the application of ⁶⁸Ga-FAPI in myocardial infarction (MI), research on the use of ¹⁷⁷Lu-FAPI for the treatment of MI is still scarce. In this study, we evaluated the effects of ⁶⁸Ga-FAPI and ¹⁷⁷Lu-FAPI in cardiac fibrosis after MI using permanent coronary artery ligation rat models. ⁶⁸Ga-FAPI-04 effectively targeted fibroblasts within the MI area. Rats treated with ¹⁷⁷Lu-FAPI-04 had a significant increase in left ventricular ejection fraction at 28 days post-MI, with no obvious kidney or liver toxicity. Magnetic resonance imaging and histological analysis revealed a reduced fibrotic area in the ¹⁷⁷Lu-FAPI group. ¹⁷⁷Lu-FAPI-04 exerted its therapeutic effect by suppressing activation and inducing apoptosis of fibroblasts. In summary, we demonstrated that ¹⁷⁷Lu-FAPI-04 could effectively target FAP and eliminate activated fibroblasts after MI, thereby contributing to the development of new strategies for the treatment of MI.