Ga-FAPI and F-FAPI PET/CT for detection of nodal metastases prior radical cystectomy in high-risk urothelial carcinoma patients.

Introduction: To determine the best therapeutic strategy for muscle-invasive bladder cancer (BC), the accuracy of lymph node staging is of paramount importance. However, diagnostic performance of conventional computed tomography in BC prior to radical cystectomy (RC) remains unsatisfactory. There is an increased interest in evaluating F-FAPI PET/CT for hybrid imaging due to their logistical advantages compared to [Ga]Ga-based FAPI tracers in clinical routine. Recently, the potential diagnostic value of [Ga]Ga-FAPI- 46 PET/CT was demonstrated in BC. Thus, we aimed to examine the diagnostic performance of [F]F-FAPI- 74 and [Ga]Ga-FAPI- 46 PET/CT for preoperative evaluation of locoregional lymph node metastases.

Methods: Fifty-one patients underwent FAPI PET/CT with either [Ga]Ga-FAPI- 46 (n = 23) or [F]F-FAPI- 74 (n = 28) prior to RC and PLND. SUV, SUV and the ratio between the SUV of lymph nodes and the SUV of the background (SUV/SUV_) were assessed. Additionally, short axis diameter (SAD) for a representative lymph node were documented in each lymph node region (n = 123) and compared to histopathological findings. Each scan was interpreted visually and quantitatively. ROC-analyses were performed to determine cut-off values with highest diagnostic accuracy.

Results: 20/123 (16.3%) lymph node regions showed UC lymph node metastases. Histopathologically positive lymph nodes were associated with a significantly higher FAPI uptake compared to negative lymph nodes regarding SUV, SUV values and SUV/SUV_ ratios. Visual analysis based on FAPI uptake showed a sensitivity and specificity, PPV and NPV of 63.6%, 95.8%, 77.7%, and 92.0% for [Ga]Ga-FAPI- 46 and 55.5%, 98.1%, 83.3%, and 93.1% for [F]F-FAPI- 74, respectively. ROC analysis revealed an optimal cut-off for SUV, SUV and SUV/SUV_ of 1.35, 1.20 and 5.95 for [Ga]Ga-FAPI- 46 and 1.55, 1.25 and 4.15 for [F]F-FAPI- 74 to discriminate between histopathologically proven lymph node metastases and non-malignant lymph nodes resulting for example using SUV in a sensitivity and specificity, PPV and NPV of 81.8%, 89.5%, 64.2%, 95.5% for [Ga]Ga-FAPI- 46 and 100%, 81.8%, 47.3%, 100% for [F]F-FAPI- 74, respectively. CT visual analysis of locoregional lymph nodes showed a sensitivity, specificity, PPV and NPV of 30.0%, 97.0%, 66.6% and 87.7%, respectively. ROC analysis regarding SAD revealed a cutoff at 0.8 cm with a sensitivity, specificity, PPV and NPV of 75.0%, 84.4%, 48.3%, 94.5%, respectively.

Conclusion: Overall, FAPI PET imaging shows a significantly higher sensitivity than CT analysis for detection of locoregional lymph node metastases in UC. [F]F-FAPI- 74 demonstrates a comparable diagnostic performance compared to [Ga]Ga-FAPI- 46. Of note, the quantitative analysis with a pre-defined SUV as well as SUV values, and SUV/SUV_ ratio-based cut-offs provided a higher sensitivity compared to visual assessment.