乳腺癌HER2的PET显像临床研究进展

乳腺癌是全世界女性发病率最高的癌症，患者中人表皮生长因子受体-2（HER2）的过表达与预后不良相关。HER2阳性乳腺癌首选曲妥珠单抗靶向治疗，曲妥珠单抗与化疗同步或序贯给药可以显著提高生存率。小于30%的HER2阳性乳腺癌患者对一线曲妥珠单抗治疗有效果，且大部分有效果患者最终会对曲妥珠单抗产生耐药性。HER2的高表达可能预测曲妥珠单抗的疗效，所以靶向治疗的成功取决于对HER2表达的准确评估。目前常规用穿刺活检获取病理组织评估HER2状态，但穿刺活检有创，不适于反复操作。此外肿瘤组织具有异质性，活检不一定能反映远处转移灶的HER2状态。与活检不同，使用靶向HER2探针的正电子发射断层扫描显像(PET)能无创、实时地评估全身HER2状态，有助于医师选择有效疗法并提供替代治疗方案。靶向HER2的抗体和小分子已用不同的放射性核素标记，用于临床前及临床PET显像研究。本文主要介绍靶向乳腺癌HER2 PET显像临床研究的最新进展，有助于医师了解分子影像在乳腺癌HER2诊疗研究中的临床结果，推进HER2 PET技术的临床转化。

PET Image Developments for HER2-Positive Breast Cancer

Breast cancer is the most frequently diagnosed cancer among females worldwide. And overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer is closely associated with poor prognosis. HER2 belongs to the epidermal growth factor receptor family of tyrosine kinases. It promotes a variety of cellular processes including cell growth, differentiation, cell survival, and cell adhesion and migration. Trastuzumab, which has been approved for the targeted therapy of HER2-positive breast cancer, is widely used now. Trastuzumab can downregulate ErbB2 receptors and cause antibody-dependent cell-mediated cytotoxicity. In clinical studies, simultaneous or sequential administration of trastuzumab with chemotherapy can significantly improve survival. However, its efficacy as a single drug has not yet reached the expected value, less than 30% of HER2-positive breast cancer patients have response to first-line trastuzumab treatment, and most of the initial responders eventually develop resistance to trastuzumab. Clinically, tumor size is assessed by imaging to evaluate trastuzumab treatment response, which is often delayed. Patients with high expression of HER2 may greatly benefit from trastuzumab, therefore, the success of HER2 targeted therapy depends on an accurate assessment of HER2 expression. At present, biopsy is routinely used to obtain pathological tissue for assessing HER2 status. However, with great disadvantages, biopsy is invasive and not suitable for repeated operations. In addition, tumor tissue is heterogeneous, as well as biopsy may not be able to reflect the HER2 status of distant metastases. Currently, compared with biopsy, positron emission tomography (PET), with a targeted HER2 probe, allows non-invasive, real-time assessment of whole body HER2 status. This technology will help physicians select patients who may benefit from HER2-targeted therapy and provide alternative treatment options for those who may not have response to it. Then it will save patients the cost and improve the prognosis of patients. Several antibodies and small molecules targeting HER2 have been labeled with different radionuclides for preclinical and clinical PET imaging studies. This review presents the latest advances in clinical molecular imaging using PET for selecting HER2-positive breast cancer.