<sup>68</sup> Ga-FAPI-46 PET/CT for cancer imaging: Results of a single-center, prospective, interventional, single-arm clinical trial.
Authors: Kim M. Pabst, Timo Bartel, Patrick Sandach, Christina Laschinsky, Manuel M. Weber, Lukas Kessler, Alina T. Küper, Boris A. Hadaschik, Claudia Kesch, Rainer Hamacher, Stefan Kasper, Lars E. Podleska, Jens T. Siveke, Markus Eckstein, Bastian von Tresckow, Sherko Kuemmel, Anke Reinacher-Schick, Waldemar Uhl, Ken Herrmann, Wofgang P. Fendler
Journal: Journal of Clinical Oncology (2025)

457 Background: Fibroblast activation protein (FAP) is highly expressed on tumor-associated fibroblasts. FAP-directed radioligand positron emission tomography ( 68 Ga-FAPI-46 PET) is a novel tool for cancer imaging. However, its diagnostic performance, especially in genitourinary (GU) cancers, is still unclear. Here, we aim to compare diagnostic performance of 68 Ga-FAPI-46 and 18 F-FDG PET, validated by histopathology. Methods: Patients (pts) at initial staging/restaging with (a) proven or suspected malignancy, (b) any tumor diameter &gt; 1 cm, (c) planned or performed biopsy/surgery within 8 weeks prior to or after 68 Ga-FAPI-46 PET, and (d) no prior external beam radiation or systemic tumor therapy within 1 month underwent 68 Ga-FAPI-46 and clinical 18 F-FDG PET on subsequent days. For comparison, patient-based and region-based (local, nodal, distant organ or soft tissue, bone) image analysis was performed by three blinded nuclear medicine physicians, separate for each PET modality. Positive predictive value (PPV) and sensitivity (SE) were evaluated based on histopathologic results, and compared in the subgroups of GU cancers, sarcoma, and others. Inter-reader reproducibility was assessed using Fleiss‘ kappa. Results: A total of n=158 pts (median age: 62 years, male/female: n=101 (63.9%)/57 (36.1%)) were enrolled. 155 (98.1%)/152 (96.2%) pts underwent 68 Ga-FAPI-46/ 18 F-FDG PET/CT. Histopathologic validation was available in n=145 (91.8%) pts. N=54 (34.2%)/28 (17.7%)/76 (48.1%) pts were diagnosed with GU cancers/sarcoma/others. Patient-based PPV/SE for 68 Ga-FAPI-46 ( 18 F-FDG) PET were 94/72% (97/71%) for GU cancers, 100/96% (100/96%) for sarcoma, and 100/91% (100/88%) for others. Region-based PPV/SE for 68 Ga-FAPI-46 ( 18 F-FDG) PET were 93/71% (97/70%) for GU cancers, 100/94% (97/90%) for sarcoma, and 99/90% (93/85%) for others. Patient-based inter-reader reproducibility for 68 Ga-FAPI-46 ( 18 F-FDG) PET was 0.71 (0.43) for GU cancers, 1.0 (0.21) for sarcoma, and 0.6 (0.53) for others. Conclusions: 68 Ga-FAPI-46 and 18 F-FDG PET demonstrate similar accuracy for tumor detection and localization of GU cancers. However, inter-reader reproducibility was superior for 68 Ga-FAPI-46 (substantial agreement) compared to 18 F-FDG PET (moderate agreement). Clinical trial information: NCT05160051 . Patient characteristics. All patients n=158 All regions n=186 Diagnosis n (pts) % (pts) n (regions) % (regions) Genitourinary CancersRenal cell carcinomaUrothelial carcinomaProstate cancerSeminomaOthers 54 3314322 34.2 20.98.91.91.31.3 63 3816414 33.9 20.48.62.20.52.2 Sarcoma 28 17.7 32 17.2 Others* 76 48.1 91 48.9 *Including breast cancer, cholangiocarcinoma, colorectal cancer, endometrial cancer, esophageal cancer, head and neck cancer, lymphoma, multiple myeloma, neuroendocrine, NSCLC, pancreatic cancer, thyroid cancer, unknown primary, others.