Initial Experience with 68 Ga-FAP-2286 PET Imaging in Patients with Urothelial Cancer.

Improved imaging modalities are needed to accurately stage patients with muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma. Imaging with small-molecule ligands or inhibitors of fibroblast activation protein (FAP) is a promising modality that has demonstrated initial efficacy across a broad range of tumors. We present our experience with the novel FAP-peptide binder ⁶⁸ Ga-FAP-2286 in patients with MIBC. Methods: Patients with histopathologically confirmed bladder cancer who had either localized disease at diagnosis (localized cohort, n = 13) or known metastatic disease (metastatic cohort, n = 8) were imaged with ⁶⁸ Ga-FAP-2286 PET as part of a clinical trial (NCT04621435). The SUV _max of ⁶⁸ Ga-FAP-2286 PET-positive lesions and lesion size were documented. In patients who had available ¹⁸ F-FDG PET performed within 45 d of ⁶⁸ Ga-FAP-2286 PET ( n = 5), uptake on the 2 scans was compared. When there was a discrepancy between imaging modalities on retrospective review, biopsy of suggestive lesions was performed as the standard of care. Results: In the metastatic and localized cohorts, 36 and 18 ⁶⁸ Ga-FAP-2286-avid lesions, respectively, were identified across multiple anatomic locations, including lymph nodes, visceral metastases, and bones. Fourteen of 36 lesions in the metastatic cohort and 14 of 18 lesions in the localized cohort were lymph nodes measuring less than 1 cm. Among lesions measuring less than 0.5 cm, 0.5-1 cm, and more than 1 cm, average SUV _max was 5.2 ± 2.6, 9.6 ± 3.7, and 13.0 ± 4.3, respectively, in the metastatic cohort and 10.5 ± 5.1, 10.8 ± 5.7, and 9.9 ± 5.4, respectively, in the localized cohort. Five patients had ¹⁸ F-FDG PET available for comparison. The average SUV _max for lesions avid on ⁶⁸ Ga-FAP-2286 PET and ¹⁸ F-FDG PET was 9.9 ± 3.4 versus 4.2 ± 1.9, respectively ( n = 16 lesions). For 3 patients in the localized cohort, ⁶⁸ Ga-FAP-2286 PET informed clinical management, including identification of both false-positive findings on ¹⁸ F-FDG PET and false-negative findings on conventional CT. Conclusion: ⁶⁸ Ga-FAP-2286 imaging is highly sensitive in patients with urothelial cancer and is effective in identifying metastatic lesions across a variety of anatomic sites, including subcentimeter lymph nodes that would not have raised suspicion on conventional scans. This novel imaging modality may inform clinical decision-making in patients with MIBC both by refining local nodal staging and by defining metastatic disease that would otherwise be undetectable on conventional imaging.
(© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)