Abstract
Purpose68Ga-FAPI (fibroblast activation protein inhibitor) is a novel and highly promising radiotracer for PET/CT imaging. The aim of this retrospective analysis is to explore the potential of FAPI-PET/CT in gynecological malignancies. We assessed biodistribution, tumor uptake, and the influence of pre- or postmenopausal status on tracer accumulation in hormone-sensitive organs. Furthermore, a comparison with the current standard oncological tracer 18F-FDG was performed in selected cases.Patients and methodsA total of 31 patients (median age 59.5) from two centers with several gynecological tumors (breast cancer; ovarian cancer; cervical cancer; endometrial cancer; leiomyosarcoma of the uterus; tubal cancer) underwent 68Ga-FAPI-PET/CT. Out of 31 patients, 10 received an additional 18F-FDG scan within a median time interval of 12.5 days (range 1–76). Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean, and tumor-to-background ratio (TBR) was calculated (SUVmax tumor/ SUVmean organ). Moreover, a second cohort of 167 female patients with different malignancies was analyzed regarding their FAPI uptake in normal hormone-responsive organs: endometrium (n = 128), ovary (n = 64), and breast (n = 147). These patients were categorized by age as premenopausal (<35 years; n = 12), postmenopausal (>65 years; n = 68), and unknown menstrual status (35–65 years; n = 87), followed by an analysis of FAPI uptake of the pre- and postmenopausal group.ResultsIn 8 out of 31 patients, the primary tumor was present, and all 31 patients showed lesions suspicious for metastasis (n = 81) demonstrating a high mean SUVmax in both the primary (SUVmax 11.6) and metastatic lesions (SUVmax 9.7). TBR was significantly higher in 68Ga-FAPI compared to 18F-FDG for distant metastases (13.0 vs. 5.7; p = 0.047) and by trend for regional lymph node metastases (31.9 vs 27.3; p = 0.6). Biodistribution of 68Ga-FAPI-PET/CT presented significantly lower uptake or no significant differences in 15 out of 16 organs, compared to 18F-FDG-PET/CT. The highest uptake of all primary lesions was obtained in endometrial carcinomas (mean SUVmax 18.4), followed by cervical carcinomas (mean SUVmax 15.22). In the second cohort, uptake in premenopausal patients differed significantly from postmenopausal patients in endometrium (11.7 vs 3.9; p < 0.0001) and breast (1.8 vs 1.0; p = 0.004), whereas no significant difference concerning ovaries (2.8 vs 1.6; p = 0.141) was observed.ConclusionDue to high tracer uptake resulting in sharp contrasts in primary and metastatic lesions and higher TBRs than 18F-FDG-PET/CT, 68Ga-FAPI-PET/CT presents a promising imaging method for staging and follow-up of gynecological tumors. The presence or absence of the menstrual cycle seems to correlate with FAPI accumulation in the normal endometrium and breast. This first investigation of FAP ligands in gynecological tumor entities supports clinical application and further research in this field.
Highlights
Regarding all cancer entities in females, breast cancer accounts for approximately 276.000 (30%) of all estimated new cases in the USA in 2020
Due to high tracer uptake resulting in sharp contrasts in primary and metastatic lesions and higher to-background ratio (TBR) than 18F-FDGPET/CT, 68Ga-fibroblast activation protein inhibitor (FAPI)-PET/CT presents a promising imaging method for staging and follow-up of gynecological tumors
The presence or absence of the menstrual cycle seems to correlate with FAPI accumulation in the normal endometrium and breast
Summary
Regarding all cancer entities in females, breast cancer accounts for approximately 276.000 (30%) of all estimated new cases in the USA in 2020. The current most frequently used diagnostical radiotracer for PET/CT regarding oncological malignancies is 18F-FDG, which accumulates in glucose-consuming tissues. The accumulation of 18F-FDG is influenced by movement, nutrition, and blood glucose levels. Beyond that, it is limited by high physiological background activity in several organs, low glucose transporter, and hexokinase activity in some malignancies as well as its imprecise differentiation between cancerous growths and acute inflammation and its missing specificity [2, 3]. In gynecological malignancies, several additional pitfalls are commonly encountered, such as potentially false-positive uptake of 18F FDG by the endometrium and ovaries in premenopausal patients as well as physiologic accumulation in several benign diseases including uterine fibroids and benign endometriotic cysts [4].
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