68Ga-FAPI and 18F-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 ¹⁸F-FAPI PET/CT for hybrid imaging due to their logistical advantages compared to [⁶⁸Ga]Ga-based FAPI tracers in clinical routine. Recently, the potential diagnostic value of [⁶⁸Ga]Ga-FAPI- 46 PET/CT was demonstrated in BC. Thus, we aimed to examine the diagnostic performance of [¹⁸F]F-FAPI- 74 and [⁶⁸Ga]Ga-FAPI- 46 PET/CT for preoperative evaluation of locoregional lymph node metastases.

Methods

Fifty-one patients underwent FAPI PET/CT with either [⁶⁸Ga]Ga-FAPI- 46 (n = 23) or [¹⁸F]F-FAPI- 74 (n = 28) prior to RC and PLND. SUV_max, SUV_mean and the ratio between the SUV_max of lymph nodes and the SUV_mean of the background (SUV_{max_lymph node}/SUV_mean__background) 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_max, SUV_mean values and SUV_{max_lymph node}/SUV_mean__background 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 [⁶⁸Ga]Ga-FAPI- 46 and 55.5%, 98.1%, 83.3%, and 93.1% for [¹⁸F]F-FAPI- 74, respectively. ROC analysis revealed an optimal cut-off for SUV_max, SUV_mean and SUV_{max_lymph node}/SUV_mean__background of 1.35, 1.20 and 5.95 for [⁶⁸Ga]Ga-FAPI- 46 and 1.55, 1.25 and 4.15 for [¹⁸F]F-FAPI- 74 to discriminate between histopathologically proven lymph node metastases and non-malignant lymph nodes resulting for example using SUV_max in a sensitivity and specificity, PPV and NPV of 81.8%, 89.5%, 64.2%, 95.5% for [⁶⁸Ga]Ga-FAPI- 46 and 100%, 81.8%, 47.3%, 100% for [¹⁸F]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. [¹⁸F]F-FAPI- 74 demonstrates a comparable diagnostic performance compared to [⁶⁸Ga]Ga-FAPI- 46. Of note, the quantitative analysis with a pre-defined SUV_max as well as SUV_mean values, and SUV_{max_lymph node}/SUV_mean__background ratio-based cut-offs provided a higher sensitivity compared to visual assessment.