Objective: Numerous studies have shown that gallium-68-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) positron emission tomography/computed tomography (PET/CT) scans would yield high intra-tumoral tracer uptake and low uptake in normal tissues as background, thus allowing for excellent visualization of lesions in the cancer microenvironment. This study set out to compare the suitability of novel⁶⁸Ga-FAPI-46 PET versus routine fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) PET and other few cases of⁶⁸Ga-DOTATATE/⁶⁸Ga-Pentixafor PET/CT for the assessment of different types of cancer.

Subjects and methods: A retrospective analysis of 11 patients (6 males, 5 females; average age: 53 years, range: 10-58 years) with histopathologically confirmed, well-differentiated adenocarcinoma, medullar thyroid cancer (MTC), papillary thyroid carcinoma (PTC), cervical, gastric, glioblastoma multiform (GBM), colon, Ewing's sarcoma, and breast cancer was performed. These patients underwent PET/CT scans using four different radiotracers (9¹⁸F-FDG, 11⁶⁸Ga- FAPI, 3⁶⁸Ga-DOTATATE, and 1⁶⁸Ga-Pentixafor). The patients' PET/CT images were visually evaluated for cancer detection, and analyzed semi-quantitatively through image- derived metrics, such as target-to-background ratio (TBR) and maximum standardized uptake value (SUVmax), for recurrence and metastasis.

Results: The study of 11 patients revealed that⁶⁸Ga-FAPI-46 was more effective than other tracers for detecting metastases, with 55 vs. 49 metastases in the lymph nodes, 4 vs. 3 in the liver, and 4 vs. 3 in the bones detected in comparison to¹⁸F-FDG. No significant differences were observed in⁶⁸Ga-DOTATATE and⁶⁸Ga-Pentixafor PET images. In addition, in five patients, the SUVmax and TBR values in⁶⁸Ga-FAPI-46 PET images were significantly higher than those in¹⁸F-FDG PET images for lymph nodes and bone metastases. Although the SUVmax in⁶⁸Ga-FAPI-46 and¹⁸F-FDG PET images for liver metastases was comparable,⁶⁸Ga-FAPI- 46 had a significantly higher TBR than¹⁸F-FDG.

Conclusion: Our findings suggest that FAPI PET/CT is not suitable for evaluating GBM and Ewing sarcoma but generally outperforms¹⁸F-FDG PET/CT in various types of breast cancer, gastrointestinal, gynecological, PTC and MTC. However, larger trials are needed to validate these preliminary findings.