HER2 表达型癌症的亲和体PET成像作为指导HER2靶向治疗的关键
Affibody PET Imaging of HER2-Expressing Cancers as a Key to Guide HER2-Targeted Therapy.
作者信息
Eissler Nina, Altena Renske, Alhuseinalkhudhur Ali, Bragina Olga, Feldwisch Joachim, Wuerth Guido, Loftenius Annika, Brun Nikolai, Axelsson Rimma, Tolmachev Vladimir, Sörensen Jens, Frejd Fredrik Y
机构信息
Affibody AB, 17165 Solna, Sweden.
Department of Oncology-Pathology, Karolinska Institutet, 17164 Solna, Sweden.
出版信息
Biomedicines. 2024 May 14;12(5):1088. doi: 10.3390/biomedicines12051088.
Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15-20% of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as HER2-positive or -negative; however, with the approval of novel treatment options, specifically the antibody-drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize the heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is molecular imaging with radiotracers. In the case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Radiotracers based on Affibody molecules, small, engineered affinity proteins with a size of ~6.5 kDa, are clinically validated molecules with favorable characteristics for imaging. In this article, we summarize the HER2-targeted therapeutic landscape, describe our experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as a novel diagnostic tool in breast cancer and beyond.
人表皮生长因子受体2(HER2)是一种主要的预后和预测标志物,在15%-20%的乳腺癌中过表达。选择接受HER2靶向治疗患者的诊断参考标准基于肿瘤活检分析。以前,患者被定义为HER2阳性或阴性;然而,随着新型治疗方案的获批,特别是抗体药物偶联物德曲妥珠单抗,许多HER2表达水平低的乳腺癌患者有资格接受HER2靶向治疗。此类患者需要通过合适的诊断方法可靠地识别出来。基于活检的诊断具有侵入性,重复活检并不总是可行的。它们无法显示HER2表达的异质性,导致大量患者被误诊。一种替代的、高度准确的诊断方法是使用放射性示踪剂进行分子成像。就HER2而言,各种研究证明了此类方法的临床实用性和可行性。基于亲和体分子的放射性示踪剂是经过临床验证的分子,亲和体分子是一种大小约为6.5 kDa的小型工程化亲和蛋白,具有良好的成像特性。在本文中,我们总结了HER2靶向治疗的现状,描述了我们在HER2成像诊断方面的经验,并回顾了目前可用的关于基于HER2-亲和体分子成像作为乳腺癌及其他疾病新型诊断工具的临床数据。