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

Background: 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. Patients and Methods: 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). Results: 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. Conclusions: 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.