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Radiolabeled cetuximab conjugates for EGFR targeted cancer diagnostics and therapy

Sihver, W.; Pietzsch, J.; Krause, M.; Baumann, M.; Steinbach, J.; Pietzsch, H. J.

Abstract

The epidermal growth factor receptor (EGFR) evolved over years one main molecular target for treatment of different cancer entities. The anti-EGFR antibody cetuximab has been approved alone or in combination with chemotherapy for palliative colorectal and head and neck squamous cell carcinoma therapy, or in combination with radiotherapy for head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab might increase the intrinsic activity in combination with the specific targeting properties of cetuximab. The article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and / or treatment on different tumor models. A promising theranostic approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. The therapeutic effect of this treatment method will be discussed. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important goal is the reduction of nonspecific uptake of 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 treatment.

Keywords: EGFR; radiolabeled cetuximab conjugates; radioimmunotherapy; cancer theranostics; external beam radiotherapy; endoradionuclide therapy

Permalink: https://www.hzdr.de/publications/Publ-19631