Physiological uterine uptake of 68Ga-FAPI-04 may limit its application in uterine pathology

Abstract

\n Purpose68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) has been useful in the imaging of desmoplastic reaction in different tumors, as well as fibrosis in inflammatory diseases. As we have found that most female patients showed avid uterine uptake of 68Ga-FAPI, we sought to further investigate the physiological uptake of 68Ga-FAPI by the uterus and analyze its characteristics in women of childbearing age, in perimenopause, and postmenopause.MethodsWe retrospectively reviewed the image data of female patients who had undergone whole-body 68Ga-FAPI-04 PET/MRI at our institute between May 22 and December 16, 2020. The clinical information of the patients, including age, stage of menstrual cycle if present, and gynecologic history, was collected. Uterine volume was calculated from MR images. The characteristics of 68Ga-FAPI-04 uterine uptake were recorded. If the patients also had undergone 18F-FDG PET/CT imaging, those image features were also recorded. The relationship of age, uterine size, surgical history, presence of leiomyomas, and 18F-FDG uptake to 68Ga-FAPI-04 uptake were further analyzed.ResultsForty-three female patients were included in this study. The number of cases with uterine malignancy and non-malignancy were two and 41, respectively. Twenty-seven patients in the benign disease group underwent simultaneous 18F-FDG PET/CT scans. Of 41 patients with benign uterine pathology, 13 patients were of reproductive age, six were perimenopausal, and 22 were postmenopausal. A total of 25 patients had undergone invasive operations, and six patients had uterine fibroids under examination. Lower 68Ga-FAPI-04 uptake (6.58\u2009±\u20093.39, n\u2009=\u200922) was noted in postmenopausal women than in reproductive and perimenopausal females (13.32\u2009±\u20093.2 and 12.98\u2009±\u20093.01, respectively, P\u2009<\u20090.05). The invasive operation or accompany with uterine fibroids may increase 68Ga-FAPI-04 uptake. 68Ga-FAPI-04 uptake was also associated with uterine volume (P\u2009<\u20090.01). There was no correlation between 18F-FDG and 68Ga-FAPI-04 accumulation in the uterus. Two patients with malignant lesions involving the uterus showed completely different imaging features on 68Ga-FAPI-04.ConclusionPhysiological uterine uptake of 68Ga-FAPI-04 limits its diagnostic value in gynecologic diseases. Age, uterine fibroids and uterine volume may influence the uptake of 68Ga-FAPI-04 in uterus. More patients with various uterine diseases could be involved to provide more differential diagnostic information.Clinical Trial RegistrationNCT04605939 and NCT04554719.