A pilot study of nectin-4-targeted radioligand [Ga]Ga-FZNR-1 in patients with pancreatic ductal adenocarcinoma: head-to-head comparison with [F]-FDG.

[PURPOSE] Nectin-4 is highly expressed in pancreatic cancer. Accurate and quantitative measurements of Nectin-4 is useful for tumor diagnosis, treatment selection, and prognostic assessment. This study aimed to evaluate the diagnostic efficacy of a Nectin-4-targeted radioligand [Ga]Ga-FZNR-1 for pancreatic ductal adenocarcinoma.

[METHODS] Thirty-three patients with PDAC were recruited and underwent head-to-head [Ga]Ga-FZNR-1 and [F]-FDG PET/CT for initial staging or to detect recurrence and metastases. PET/CT findings were confirmed by histopathology or follow-up imaging. Thirteen primary and metastatic lesions from the 33 patients were evaluated for Nectin-4 immunohistochemical expression.

[RESULTS] [F]-FDG and [Ga]Ga-FZNR-1 PET/CT were comparable in detecting primary tumors, lymph node metastases, and distant metastases (96.00% [24/25] vs. 92.00% [23/25], 88.24% [15/17] vs. 82.35% [14/17], 95.24% [20/21] vs. 95.24% [20/21]). [Ga]Ga-FZNR-1 PET/CT demonstrated slightly higher specificity and accuracy than [F]-FDG PET/CT for distant metastases (100.00% vs. 93.75%, 100.00% vs. 96.97%). The receiver operating characteristic (ROC) curve revealed that [Ga]Ga-FZNR-1 had high sensitivity and specificity in detecting Nectin-4-expressing lesions. Both SUV and TBR on [Ga]Ga-FZNR-1 PET/CT were significantly and positively correlated with the expression of Nectin-4 (both r = 0.89, both p < 0.001).

[CONCLUSION] [Ga]Ga-FZNR-1 is excellent in diagnosing primary, metastatic, and recurrent lesions of PDAC. In particular, it may be a useful complement in patients with distant metastases that cannot be detected by [F]-FDG PET/CT. [Ga]Ga-FZNR-1 PET/CT could quantify the Nectin-4 expression. Moreover, [Ga]Ga-FZNR-1 PET/CT may have potential predictive value in the prognostic assessment of patients with PDAC.