Tumor Characterization by [68Ga]FAPI-46 PET/CT Can Improve Treatment Selection for Pancreatic Cancer Patients: An Interim Analysis of a Prospective Clinical Trial

Correct and timely diagnosis of pancreatic cancer (PC) is essential for treatment selection but is still clinically challenging. Standard-of-care imaging methods can sometimes not differentiate malignancies from inflammatory lesions or detect malignant transformation in premalignant lesions. This interim analysis of a prospective clinical trial aimed to evaluate the diagnostic accuracy of [⁶⁸Ga]fibroblast activation protein inhibitor (FAPI)-46 PET/CT for PC and determine the sample size needed to demonstrate whether this imaging technique improves the characterization of equivocal lesions detected by standard-of-care imaging methods. Methods: [⁶⁸Ga]FAPI-46 PET/CT imaging was performed on 30 patients scheduled for surgical resection of suspected PC. Target lesions were delineated, SUV_max and SUV_mean were determined, and the results were compared with those of standard-of-care imaging. Receiver operating characteristics were calculated for the whole cohort and a subcohort of 11 patients with an equivocal clinical imaging work-up preoperatively. Postoperative histopathologic findings served as a reference standard, and the statistical power was determined. Results: Histopathologic examination revealed malignancy in 20 patients and benign lesions in 10 patients. Significantly elevated [⁶⁸Ga]FAPI-46 uptake was observed in malignant tumors compared with benign lesions (P < 0.001). Receiver-operating-characteristic analyses established optimal cutoffs for both SUVs for differentiation of malignant from nonmalignant pancreatic tumors. The optimal SUV_max cutoff was 10.2 and showed 95% sensitivity and 80% specificity for the whole cohort, as well as 100% diagnostic accuracy when considering the subcohort with equivocal imaging work-up only. For sufficient statistical power, 38 equivocal observations are needed. Conclusion: We conclude that [⁶⁸Ga]FAPI-46 PET/CT can accurately differentiate malignant from benign pancreatic lesions deemed equivocal by standard-of-care imaging. This trial will therefore continue to recruit a total of 120 patients to reach those 38 equivocal observations needed for sufficient statistical power. On the basis of our findings, we propose that [⁶⁸Ga]FAPI-46 PET/CT not only can be clinically applied as a complement but also could become a necessary tool when standard-of-care imaging is inconclusive.