In Vivo Imaging of GLP-1R with a Targeted Bimodal PET/Fluorescence Imaging Agent

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• 作者：Christian Brand ; Dalya Abdel-Atti ; Yachao Zhang ; Sean Carlin ; Susan M. Clardy ; Edmund J. Keliher ; Wolfgang A. Weber ; Jason S. Lewis ; Thomas Reiner
• 刊名：Bioconjugate Chemistry
• 出版年：2014
• 出版时间：July 16, 2014
• 年：2014
• 卷：25
• 期：7
• 页码：1323-1330
• 全文大小：402K
• ISSN：1520-4812

文摘

Accurate visualization and quantification of 尾-cell mass is critical for the improved understanding, diagnosis, and treatment of both type 1 diabetes (T1D) and insulinoma. Here, we describe the synthesis of a bimodal imaging probe (PET/fluorescence) for imaging GLP-1R expression in the pancreas and in pancreatic islet cell tumors. The conjugation of a bimodal imaging tag containing a near-infrared fluorescent dye, and the copper chelator sarcophagine to the GLP-1R targeting peptide exendin-4 provided the basis for the bimodal imaging probe. Conjugation was performed via a novel sequential one-pot synthetic procedure including ⁶⁴Cu radiolabeling and copper-catalyzed click-conjugation. The bimodal imaging agent ⁶⁴Cu-E4-Fl was synthesized in good radiochemical yield and specific activity (RCY = 36%, specific activity: 141 渭Ci/渭g, >98% radiochemical purity). The agent showed good performance in vivo and ex vivo, visualizing small xenografts (<2 mm) with PET and pancreatic 尾-cell mass by phosphor autoradiography. Using the fluorescent properties of the probe, we were able to detect individual pancreatic islets, confirming specific binding to GLP-1R and surpassing the sensitivity of the radioactive label. The use of bimodal PET/fluorescent imaging probes is promising for preoperative imaging and fluorescence-assisted analysis of patient tissues. We believe that our procedure could become relevant as a protocol for the development of bimodal imaging agents.