Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, Dresden 01328, Germany.
Department of Radiation Oncology and OncoRay, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany.
Pharmaceuticals (Basel). 2014 Mar 5;7(3):311-38. doi: 10.3390/ph7030311.
The epidermal growth factor receptor (EGFR) has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a) chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b) with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment.
表皮生长因子受体 (EGFR) 多年来已成为治疗不同癌症实体的主要分子靶标。在这方面，抗 EGFR 抗体西妥昔单抗已被批准单独或与以下药物联合使用：(a) 用于治疗结直肠癌和头颈部鳞状细胞癌的化疗，(b) 用于治疗头颈部鳞状细胞癌的外部放射治疗。放射性核素与西妥昔单抗的结合以及该抗体的特异性靶向特性可能会提高其治疗效率。本文综述了用放射性标记的西妥昔单抗进行的用于不同肿瘤模型的成像和/或治疗的临床前研究。一种特别有前途的方法似乎是用治疗性放射性核素标记的西妥昔单抗联合外部放射治疗进行治疗。目前的数据支持肿瘤微环境对治疗反应的重要影响，这需要在患者中进一步验证。另一个重要的挑战是减少放射性物质在肝脏等代谢器官和骨髓、肾脏等放射敏感器官中的非特异性摄取。总的来说，将诊断、治疗和监测整合为一种治疗方法似乎是改善个体化癌症治疗的一种很有前途的策略。
