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Radioimmunotherapy of the mice bearing breast tumor with Herceptin labeled 177Lu

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Author(s): Samira Rasaneh | Hossein Rajabi | Mohammad Hossein Babaei | Fariba Johari | Shahab Sheybani | Seyed Hasan Mirfallah | Mohamad Mazidi | Sepideh Khoshbakht | Yaser Tavakoli

Journal: Iranian Journal of Nuclear Medicine
ISSN 1681-2824

Volume: 18;
Issue: Suppl 1;
Start page: 53;
Date: 2010;
Original page

Keywords: Radioimmunotherapy | Lutetium-177 | Herceptin | Trastuzumab

ABSTRACT
Introduction: Trastuzumab (trade name Herceptin) is a humanized IgG1 monoclonal antibody directed against the extracellular domain of the Human Epidermal growth factor Receptor 2 (HER2). HER2 receptor is overexpressed in 20-30% of the early-stage breast cancers and these patients may be candidates for Herceptin treatment. However, due to the cardiotoxicity of Herceptin, some patients cannot tolerate the treatment due to pre-existing heart conditions. Radioimmunotherapy (RIT) is a targeted treatment that has potential to augment the efficacy of conventional monoclonal antibodies. In radioimmunotherapy, a radioisotope is coupled to a monoclonal antibody to form a tumor-specific target agent. In the present study, we have labeled trastuzumab with lutetium-177 (a beta emitter suitable for therapy), preformed the biodistribution study and investigated its therapeutic efficacy in mice bearing tumor. Methods: Herceptin was labeled with Lutetium-177 via DOTA as chelator. Radiochemical purity, immunoreactivity and stability of 177Lu-Herceptin were determined. The biodistribution and imaging studies were performed in mice bearing breast tumor. Radioimmunotherapy(5.5 and 7.4 MBq/mouse) and dosimetry was performed in mice bearing tumor. Results: Number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81% after 4 days suggested that 177Lu-Herceptin could be used as a radioimmunotherapy agent. The good tumor uptake in biodistribution studies was agreed with gamma camera images after 7 days. Reductions of 81% and 98% in the mean tumor volume for the group that received 177Lu-Herceptin [7.4 MBq] were observed at 42 and 45 days after treatment respectively. Conclusion: The results showed that 177Lu-Herceptin could be considered possibly in humans as a new radiopharmaceutical agent for using in radioimmunotherapy of breast cancer.
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