HER2-targeted SPECT imaging of nude mice with colon cancer xenografts using 125I-Herceptin
JOURNAL OF NUCLEAR MEDICINE(2018)
摘要
1299 Aim: R2-targeted SPECT imaging of nude mice with colon cancer xenografts using 125I-Herceptin\n Objectives: The overexpression of human epidermal growth factor receptor 2 (HER2) is associated with poor clinical outcomes, and has been found in many types of cancer, including breast cancer, ovarian cancer, endometrial cancer and colorectal cancer. Herceptin (Pertuzumab) was the first FDA-approved humanized monoclonal antibody for the targeted therapy of HER2+ breast cancer. Since HER2 overexpression also occurs in colorectal cancer, it is expected that 125I-labeled Herceptin targeting HER2 can provide SPECT imaging of colon cancer xenografts.\n Methods: Herceptin was radiolabeled with 125I using the Iodogen\n Methods: The expression level of HER2 in colon carcinoma MC38 cells was detected by Western blotting, and MC38 cells were injected subcutaneously into the nude mice for the establishment of colon cancer xenografts model. The specificity of 125I-Herceptin was assessed using the in vitro cell binding assay. The SPECT imaging studies were performed in nude mice with colon cancer xenografts at different time points post-injection. For the blocking studies, excessive Herceptin was intravenously injected into the nude mice, 24 hours prior to 125I-Herceptin administration.\n Results: The labeling yield of 125I-Herceptin exceeded 98% and the radiochemical purity was greater than 95%. HER2 was expressed in MC 38 cells. 125I-Herceptin showed excellent HER2-binding specificity both in vitro and in vivo. SPECT imaging of nude mice with colon cancer xenografts using 125I-Herceptin revealed that the tumors were clearly visualized at 6 h, and the tumor uptake reached peak at 24 h after injection. In addition, the maximum uptake was reduced at 24 h time point in blocking studies suggesting specificity of 125I-Herceptin to HER2.\n Conclusions: Our study suggests 125I-Herceptin can be used as an effective SPECT probe for the non-invasive detection of colon cancer expressing HER2. Research Support: This work is supported by the National Natural Science Foundation of China (Grant No. 81471714) and the Staring Foundation for Young Researcher of Changhai Hospital (Grant No. CH201714).
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关键词
colon cancer xenografts,spect imaging,nude mice,i-herceptin
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