방사선의학 웹진

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Abstract
Antibody-drug conjugates (ADCs) have drawn a lot of attention in the field of cancer therapy due to their improved efficacy and reduced side effects compared to traditional therapeutic antibodies or chemotherapeutics. However, cancer patients still develop resistance against ADCs and there is an urgent need for the development of strategies to reinforce ADC efficacy. Radiolabeling of an antibody with therapeutic radioisotopes (e.g., 177Lu or 225Ac) can be considered an option. Herein, we synthesized radiolabeled ADCs and evaluated their potential therapeutic efficacies in vitro and in vivo for cancer therapy. New trastuzumab-based ADCs utilizing fendiline or gemifloxacin as drug moieties were developed, and they were decorated with therapeutic radionuclide 177Lu or 225Ac. Anticancer effects of radiolabeled ADCs were evaluated using human epidermal growth factor receptor 2 (HER2) expressing cancer cells and compared to that of cold ADCs. Radiolabeled versions of newly synthesized ADCs showed significantly improved anticancer efficacy compared to unlabeled ADCs, especially when they were armed with 225Ac, demonstrating the great potential of radiolabeled ADCs in cancer therapy. This study offers an effective strategy for improving the therapeutic efficacy of ADCs by fortifying them with radionuclides.

Affiliations

Chi Soo Kang 1 2, Do Hyeon Kim 1 3, Hwisoo Lim 1 2, Sunkyo Kim 1 2, Muath Almaslamani 1 2, Choong Mo Kang 1 2, Sang-Keun Woo 1 2
1Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
2Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon 34113, Republic of Korea.
3Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.