Abstract 3349: Optimizing radioimmunotherapy techniques for the alpha-emitter 225Actinium

Introduction: Radioimmunotherapy (RIT) is a potent therapeutic technique that may be applicable to the treatment of numerous human cancers. Currently available RIT therapies employ beta- and alpha-emitting radionuclides. Alpha-emitters, such as 225Actinium (225Ac), have promising advantages over beta-emitters RIT such high linear energy transfer and independence of the tumor oxygenation status. RIT using 225Ac radionuclide directed by the monoclonal antibodies trastuzumab or panitumumab may provide effective, targeted antineoplastic effects. Methods: Antibodies trastuzumab to HER2/neu and panitumumab to EGFR were conjugated to the bifunctional ligands NETA, DOTA, DECA, DEPA and DETA. The conjugates were labeled with 225Ac at room temperature and 37°C. At selected time points, the mixture was analyzed by instant thin layer chromatography (ITLC). Radiolabeling reaction kinetics and yields were calculated for 225Ac and for its daughter isotopes 221Francium (221Fr) and 213Bismuth (213Bi) using the energy discrimination function of the multichannel analyzer in the gamma counter. Summary of the new data: Radiolabeling with Actinium was effective for several ligand-antibody combinations and completed within 30 min. Radiolabeling yields for 225Ac and it daughters 221Fr and 213Bi were most robust for NETA and DECA conjugates to trastuzumab and panitumumab, labeled at 37°C. Conclusion: Several novel ligands were evaluated for radiolabeling of monocloncal antibodies trastuzumab or panitumumab with 225Ac radionuclide and demonstrated fast kinetics of radiolabeling. Potential for targeted therapeutic applications will be explored in future experiments. Citation Format: Ricklie A. Julian, Chi Soo Kang, Xiang Sun, Hyun A. Song, Ekaterina Revskaya, Hyun-Soon Chong, Ekaterina Dadachova. Optimizing radioimmunotherapy techniques for the alpha-emitter 225Actinium. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3349. doi:10.1158/1538-7445.AM2015-3349