Non-tumoral uptake of Ga-68-FAPI-04 PET: A retrospective study

ObjectiveFibroblast activation protein (FAP)-targeting radiopharmaceutical based on the FAP-specific inhibitor (FAPI) is considered as a potential alternative agent to FDG for tumor-specific imaging. However, FAP is also expressed in normal adult tissues. The aim of this study was to explore the image features of non-tumoral regions with high uptake of Ga-68-FAPI-04 in positron emission tomography (PET) imaging and to reveal the physiological mechanisms of these regions. MaterialA total of 137 patients who underwent whole-body Ga-68-FAPI-04 PET/MR (n=46) or PET/CT (n=91) were included in this retrospective study. Three experienced nuclear medicine physicians determined the non-tumoral regions according to other imaging modalities (CT, MRI, F-18-FDG PET, or ultrasound), clinical information, or pathological results. The regions of interest (ROIs) were drawn manually, and the maximum standardized uptake value (SUVmax) was measured. ResultsA total of 392 non-tumoral uptake regions were included in this study. The included physiological regions were uterus (n=38), submandibular gland (n=118), nipple (n=37), gingiva (n=65), and esophagus (n=31). The incidence of Ga-68-FAPI-04 uptake in physiological regions was independent of age, the tracer uptakes in the gingiva and esophagus were more common in male patients (p=0.006, 0.009), while that in the nipple was more common in female patients (p < 0.001). The included benign regions were inflammatory lymph node (n =10), pneumonia (n=13), atherosclerosis (n=10), pancreatitis (n=18), osteosclerosis (n=45), and surgical scar (n=7). No significant difference was observed in SUVmax between physiological and benign regions. ConclusionsA number of organs exhibit physiological uptakes of Ga-68-FAPI-04. Our study showed that regions with high Ga-68-FAPI-04 uptake did not necessarily represent malignancy. Being familiar with physiological and typical benign Ga-68-FAPI-04 uptake regions can be helpful for physicians to interpret images and to make an accurate diagnosis.