PET imaging of a 68Ga labeled modified HER2 affibody in breast cancers: from xenografts to patients

作者：Yuping Xu, Lizhen Wang, Donghui Pan, Chunjing Yu, Baoming Mi, Qianhuan Huang, Jie Sheng, Junjie Yan, Xinyu Wang, Runlin Yang, Min Yang · 发表于：British Journal of Radiology · 年份：2019 · DOI：10.1259/bjr.20190425 · 被引用次数：33 · 研究领域：Radiopharmaceutical Chemistry and Applications、Monoclonal and Polyclonal Antibodies Research、HER2/EGFR in Cancer Research

Objective: Overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancers provides promising opportunities for imaging and targeted therapy. Developing HER2 targeted positron emission tomography (PET) probes might be benefit for management of the disease. Small high-affinity scaffold proteins, affibodies, are ideal vectors for imaging HER2 overexpressed tumors. Despite of the initial success on development of 18F labeled ZHER2:342 affibody, the tedious synthesis producers, low yields and unfavorable pharmacokinetics may hinder the clinical use. 68Ga is an attractive positron emitter for PET imaging. A simple preparation of 68Ga labeled ZHER2:342 analog, 68Ga-NOTA-MAL-Cys-MZHER2:342, was reported in the study. The in vivo performances of the tracer for assessing HER2 status in breast cancers were also evaluated. Methods: NOTA-MAL conjugated Cys-MZHER2:342 was radiolabeled with 68Ga. The probe was evaluated by in vitro tests including stability and cell binding studies in breast cancer cells with different HER2 levels. In vivo evaluation was performed in mice bearing tumors using microPET imaging and biodistribution experiments. A PET/CT imaging study was initially performed in patients with breast cancers. Results: The tracer was synthesized in a straightforward chelation method with satisfactory non-decay corrected yield (81±5%) and radiochemical purity (>95%). In vivo micro-PET imaging showed that HER2 high levels expressed BT474 xenografts were m...