68Ga-FAPI-PET/CT in patients with various gynecological malignancies

Abstract

Purpose 68Ga-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 methods A 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. Results In 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. Conclusion Due 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.

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

“…An investigation of various malignancies including breast cancer (n = 14), ovarian cancer (n = 9), cervical cancer (n = 4), endometrial cancer (n = 2), leiomyosarcoma of the uterus (n = 1) and tubal cancer (n = 1) described impressive SUV metrics and TBRs and was equal or superior to FDG. Furthermore, immunohistochemistry staining demonstrated a strong FAP expression in ovarian cancer, breast cancer and leiomyosarcoma of the uterus, which is in concordance with previous studies [74]. With respect to ovarian cancer, FAPI-PET/CT might be of particular interest as preceding studies determined its presence in 97% of all ovarian cancers and showed a correlation between FAP and a poor clinical prognosis, chemotherapy resistance and shorter time until recurrence [4,[118][119][120][121][122].…”

“…Hormone-responsive organs seem to be associated with an increased uptake on FAPI-PET/CT. In an analysis regarding FAPI uptake in the breast, ovary and uterus, statistically significant differences were seen in the breast and ovaries with a stronger uptake in premenopausal patients [74]. Additionally, the uptake might correlate with the menstrual cycle.…”

“…With respect to ovarian cancer, FAPI-PET/CT might be of particular interest as preceding studies determined its presence in 97% of all ovarian cancers and showed a correlation between FAP and a poor clinical prognosis, chemotherapy resistance and shorter time until recurrence [4,[118][119][120][121][122]. In terms of ovarian cancer, the uptake of FAPI-PET/CT was intense [74]. In addition, due to the limited therapeutic options for ovarian cancer, FAPI offers a potential therapeutic target as FAP expression is absent in healthy ovaries [120].…”

FAP imaging in rare cancer entities—first clinical experience in a broad spectrum of malignancies

“…This indicates that approximately 7000 rare diseases have an impact on about 30 million people in the EU, highlighting the importance of a reliable and accurate staging tool despite low incidences [1]. A novel nuclear tracer, fibroblast activation protein inhibitor (FAPI), presented highly promising results in previously published analyses for imaging different types of cancer [2][3][4]. FAP, a cell membrane-bound type II serine protease, is overexpressed by cancer-associated fibroblasts (CAFs) which are associated with cancer-promoting processes and poor prognosis [5,6].…”

New Frontiers in Cancer Imaging and Therapy Based on Radiolabeled Fibroblast Activation Protein Inhibitors: A Rational Review and Current Progress

“…FAP imaging using [ 68 Ga]Ga-FAPI PET/CT was further investigated in multiple sarcomas [ 139 ], gynecological tumors [ 140 ], and pancreatic ductal adenocarcinomas (PDAC) [ 141 ]. These preliminary clinical data also suggest that FAPI ligands may have the potential to highly contribute to the diagnosis and potential therapy of those types of cancer; however, larger comprehensive studies are required for confirmation.…”