EGFR Targeting by 177Lu-Cetuximab Inhibits Proliferation of Colon Cancer Cells Lines
Publish Year: 1396
نوع سند: مقاله کنفرانسی
زبان: English
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شناسه ملی سند علمی:
CBGCONF04_047
تاریخ نمایه سازی: 22 دی 1396
Abstract:
Background: Elevated expression of EGFR is a frequent genetic abnormality seen in colon cancer. The monoclonal antibody cetuximab binds to EGFR and thus provides an opportunity to create both imaging and therapies that target this receptor. The main goal of this study was to optimize the radioimmunoconjugation of monoclonal anti-EGFR with 177Lu as a potential molecular tracer for colon cancer radioimmunotherapy(RIT). Methods: Cetuximab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. The integrity of the radiolabeled antibody was checked by SDS-PAGE. Biodistribution study of 177Lu-DOTA –cetuximab was performed in mice at 2, 24, 48 and 72 hours after injection. Immunoreactivity and toxicity of the complex were tested on SW480 colon cancer cell line. Results: The efficiency of antibody labeling was more than 98%±1. The in vitro stability of the labeled product inhuman serum after 96h was 83 ±2%. There was no fragmentation in the labeled antibody during SDS-PAGE protocol. The highest %ID/g was observed in the blood, liver and lungs. The immunoreactivity of the complex was 91±1 %. At a concentration of 1 nM, the complex killed 22±3% of SW480 cells. At 16 nM, 82±5% of the cells were killed. Discussion: Radioconjugate of cetuximab and 177Lu were successfully produced and characterized as radiopharmaceutical. The results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against colon cancer.
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Authors
Kamal Yavari
Department Nuclear Sciences and Technology Research Institute, Tehran, Iran