Abstract
PURPOSE: Human epidermal growth factor receptor 2 (HER2) is a promising therapeutic target in urothelial carcinoma (UC). We aimed to evaluate the feasibility of 68Ga-HER2 affibody PET/CT in assessing HER2 expression and tumor heterogeneity, and to explore its utility for guiding HER2-targeted therapy in UC. PATIENTS AND METHODS: Thirty-two patients with UC who underwent 68Ga-HER2-affibody and 18F-FDG-PET/CT were prospectively recruited from September 2024 to April 2025. Semiquantitative PET/CT parameters (SUVmax, SUVmean, TMR, HER2-TV/MTV, and TL-HER2/TLG) were analyzed across HER2 statuses. Intrapatient heterogeneity of SUVmax across lesions was assessed by the coefficient of variation (CV). RESULTS: HER2-positive patients demonstrated significantly higher SUVmax, SUVmean, TMR, and HER2-TV of 68Ga-HER2-affibody PET/CT compared with HER2-negative patients (all P < 0.05). No significant differences were observed in 18F-FDG PET/CT except for MTV and TLG (P < 0.05). ROC analysis revealed strong predictive value for HER2-SUVmax (AUC: 0.87) and TMR (AUC: 0.88) in differentiating HER2-negative/positive. Stepwise increases in HER2-PET/CT parameters were observed across HER2 immunohistochemistry statuses (Ptrend < 0.05). HER2-PET/CT demonstrated high heterogeneity, with a median SUVmax CV of 49.7% (IQR: 29.7%-64%) across intrapatient metastatic lesions. In 7 patients receiving HER2-target therapy, 2 patients with low HER2 uptake on PET/CT developed progressive disease, whereas 4 of 5 patients with high uptake achieved a partial response. CONCLUSIONS: 68Ga-HER2 affibody PET/CT is a feasible method to detect the HER2 status and heterogeneity in UC patients noninvasively. This method provides a valuable tool for identifying patients who benefit from HER2-target therapy.