PSMA PET/CT for Improved Staging Accuracy and Imaging of Neovascularization-associated Features in Primary Lung Cancer.

Abstract

Prostate-specific membrane antigen (PSMA), expressed in neovascular endothelial cells of various malignancies including lung cancer (LC), highlights its potential as a biomarker for neovascularization. This study aimed to investigate the diagnostic efficacy of PSMA PET/CT in primary lung cancer (PLC), as well as to explore its role in staging and neovascularization detection in PLC. This retrospective study included 39 patients (27 with PLC, 12 with benign lesions) who underwent PSMA PET/CT, with or without FDG PET/CT, between April 2021 and July 2024. Lesion characteristics and immunohistochemistry for PSMA, VEGFA, and CD31 were assessed in 11 surgical cases. Statistical analyses included the Mann-Whitney U test and Spearman correlation ( p <0.05). Our study demonstrated that PSMA PET/CT effectively differentiates PLC from benign lesions, achieving a high SUVmax AUC of 0.89 (cutoff: 2.3 g/mL) and a mediastinal lymph node (LN) identification AUC of 0.86 (cutoff: 2.5 g/mL). Compared with FDG PET/CT, PSMA PET/CT exhibited a lower false-positive LN detection rate, resulting in N-stage reclassification in 60% (12/20) of cases. PSMA PET uptake in intrapulmonary lesions correlated significantly with the PSMA H-score (R=0.63, p <0.05), CD31-assessed microvessel density (R=0.77, p <0.01), and VEGFA H-score (R=0.65, p <0.05), while FDG uptake showed no correlation. PSMA PET shows higher uptake in PLC than in benign lesions, improves LN staging, and reveals its potential as a biomarker for neovascularization and treatment optimization in LC.