68Ga-FAPI-04

Anthracycline chemotherapy, widely used in cancer treatment, poses a significant risk of cardiotoxicity that results in functional decline. Current diagnostic methods poorly predict cardiotoxicity because they do not detect early damage that precedes dysfunction. Positron emission tomography (PET) is well suited to address this need when coupled with suitable imaging biomarkers. We used PET to evaluate cardiac molecular changes in male C57BL/6J mice exposed to doxorubicin (DOX). These mice initially developed cardiac atrophy, experienced functional deficits within 10 weeks of treatment, and developed cardiac fibrosis by 16 weeks. Elevated cardiac uptake of [68Ga]Ga-FAPI-04, a PET tracer targeting fibroblast activation protein α (FAP), was evident by 2 weeks and preceded the onset of functional deficits. Cardiac PET signal correlated with FAP expression and activity as well as other canonical indicators of cardiac remodeling. By contrast, cardiac uptake of [18F]DPA-714 and [18F]MFBG, which target translocator protein 18 kDa and the norepinephrine transporter, respectively, did not differ between the DOX animals and their controls. These findings identify FAP as an early imaging biomarker for DOX-induced cardiac remodeling in males and support the use of FAP PET imaging to detect some cancer patients at risk for treatment-related myocardial damage before cardiac function declines.

A 70-year-old man, who underwent radical surgery for left lower lung squamous cell carcinoma 4 years ago and received sintilimab therapy 3 months ago for suspected hilar lymph node metastasis, presented with multiple liver lesions detected by MRI. Laboratory tests showed abnormally elevated eosinophil count with 4.89×10 9 /L. 18 F-FDG PET/CT imaging demonstrated significantly high FDG-avid in the liver lesions, while 68 Ga-FAPI-04 PET/MRI imaging revealed slight FAPI uptake. Histopathological examination of the liver biopsy indicated chronic granulomatous inflammation with necrosis and a large number of eosinophils. Combining with these tests, eosinophilic liver infiltration induced by the immune checkpoint inhibitor was diagnosed.