Multidisciplinary ⁶⁸Ga-HER2-Affibody PET/CT Study Enables Noninvasive Evaluation of HER2 Expression in Urothelial Carcinoma
A multidisciplinary team led by Professors Xuesong Li and Qi Tangfrom the Institute of Urology and Department of Urology, Peking University First Hospital, in collaboration with Professor Jianhua Zhang’s team from the Department of Nuclear Medicine and Professor Xiaoying Li’s team from the Department of Radiation Oncology, has published an original research article in Clinical Nuclear Medicine (Impact Factor: 9.6), the official journal of the Society of Nuclear Medicine and Molecular Imaging.This study systematically evaluated the feasibility of ⁶⁸Ga-HER2-affibody PET/CT for the noninvasive assessment of HER2 expression and intratumoral heterogeneity in urothelial carcinoma, offering a novel strategy for patient selection in HER2-targeted therapies.
Urothelial carcinoma is one of the most common malignancies of the urinary system, with a dismal 5-year survival rate of approximately 5% in patients with advanced disease. HER2 represents an important therapeutic target, and its expression status is critical for the application of HER2-targeted agents such as disitamab vedotin. However, HER2 expression in urothelial carcinoma is characterized by pronounced spatial and temporal heterogeneity: discordance between primary tumors and metastatic lesions, potential conversion of HER2 status between initial and recurrent disease, and the inability of single-site biopsy to reflect the global tumor profile.
Conventional HER2 assessment relies heavily on pathological biopsy, which is invasive, limited in sampling scope, and inadequate for capturing tumor heterogeneity. In contrast, ⁶⁸Ga-HER2-affibody PET/CT offers a promising noninvasive, whole-body imaging approach for comprehensive evaluation of HER2 expression.
⁶⁸Ga-HER2-Affibody PET/CT Identifies Urothelial Carcinoma Lesions With Differential HER2 Expression
In this prospective study, 32 patients with urothelial carcinoma were enrolled and underwent dual-tracer PET/CT imaging using ⁶⁸Ga-HER2-affibody and ¹⁸F-FDG. Comparative analyses demonstrated that HER2-positive patients exhibited significantly higher SUVmax and tumor-to-mediastinum ratio (TMR) values on ⁶⁸Ga-HER2-affibody PET/CT than HER2-negative patients. Receiver operating characteristic (ROC) analysis showed excellent diagnostic performance, with TMR achieving an AUC of 0.88 and SUVmax an AUC of 0.87 for distinguishing HER2 status.
Importantly, the study provided the first in vivo visualization of marked HER2 heterogeneity in urothelial carcinoma, with the coefficient of variation of SUVmax among metastatic lesions reaching as high as 49.7%. Among seven patients who subsequently received HER2-targeted therapy, those with high tracer uptake on ⁶⁸Ga-HER2-affibody PET/CT predominantly achieved partial responses, whereas all patients with low uptake experienced disease progression—suggesting a preliminary predictive value for treatment response.
Toward Molecular Imaging–Guided Precision Management
This study introduces a novel, noninvasive, whole-body imaging tool for dynamic assessment of HER2 expression, with the potential to overcome the inherent limitations of traditional biopsy-based methods. By enabling visualization of HER2 distribution and heterogeneity across all disease sites, ⁶⁸Ga-HER2-affibody PET/CT may facilitate more precise patient selection, treatment decision-making, and response monitoring for HER2-targeted therapies.
Looking ahead, the research team plans to center future efforts on HER2-targeted treatment and establish a full-cycle precision management framework encompassing patient screening, therapeutic decision-making, and efficacy monitoring. Through continued innovation and multidisciplinary collaboration, the team aims to translate molecular imaging–guided precision strategies into routine clinical practice, advancing the standard of care for urothelial carcinoma and ultimately benefiting a broader patient population.
