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Preclinical characterization and validation of a dual-labeled trastuzumab-based imaging agent for diagnosing breast cancer 被引量:2
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作者 Xuejuan Wang melissa B. Aldrich +1 位作者 milton V. marshall eva m. sevick-muraca 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2015年第1期74-82,共9页
Objective: The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was ... Objective: The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was to synthesize and optimize a dual-labeled trastuzumab-based imaging agent that can be used to validate an optical imaging agent with potential use in identifying tumor metastases in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. Methods: [111In]-DTPA-trastuzumab-IRDye 800 was synthesized by a three-step procedure. Purity, stability, immunoreactivity, internalization and biodistribution were explored in HER2+ SKBR-3 cells. Biodistribution of [111In]-DTPA-trastuzumab-IRDye 800 was performed in a SKBR-3 xenograft model. Results: [111In]-DTPA-trastuzumab-IRDye 800 demonstrated high purity by both chemical and fluorometric determinations. Both flow cytometry and the Lindmo assay demonstrated a high binding affinity of [111In]-DTPA-trastuzumab-IRDye 800 to HER2-overexpressing cells. The dual-labeled conjugate was stable in PBS, but not in serum after 24 h at 37 ℃. Larger molecules (〉150 kD) were seen after a 24 h-incubation in human serum. Biodistribution studies revealed tumor-specific accumulation of [111In]-DTPA- trastuzumab-IRDye 800 in SKBR-3 tumors, and tumor uptakes at 24 and 48 h were (12.42±1.72)% and (9.96±1.05) %, respectively, following intravenous administration. The tumor-to-muscle ratio was 9.13±1.68 at 24 h, and increased to 12.79±2.13 at 48 h. Liver and kidney showed marked uptake of the dual-labeled imaging agent. Conclusions: [111In]-DTPA-trastuzumab-IRDye 800 is an effective diagnostic biomarker that can be used to validate dual-labeled, molecularly targeted imaging agents and can allow these agents to be translated into clinical practice for identifying HER2+ lesions. 展开更多
关键词 Dual-labeling TRASTUZUMAB human epidermal growth factor receptor 2 (HER2) near-infrared opticalimaging (NIR optical imaging) RADIOIMMUNOSCINTIGRAPHY
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