⁶⁸ Ga-FAPI-46 PET/CT for cancer imaging: Results of a single-center, prospective, interventional, single-arm clinical trial.

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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 > 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.