期刊
BIOCONJUGATE CHEMISTRY
卷 25, 期 7, 页码 1323-1330出版社
AMER CHEMICAL SOC
DOI: 10.1021/bc500178d
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- Radiochemistry and Molecular Imaging Probes Core [P30 CA008748-48, S10 RR020892-01]
- National Institute of Health [K25 EB016673]
- Brain Tumor Center of Memorial Sloan Kettering Cancer Center
- Center for Molecular Imaging and Nanotechnology of Memorial Sloan Kettering Cancer Center
- Small Animal Imaging Core
Accurate visualization and quantification of beta-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 Cu-64 radiolabeling and copper-catalyzed click-conjugation. The bimodal imaging agent Cu-64-E4-Fl was synthesized in good radiochemical yield and specific activity (RCY = 36%, specific activity: 141 mu Ci/pg, >98% radiochemical purity). The agent showed good performance in vivo and ex vivo, visualizing small xenografts (<2 mm) with PET and pancreatic beta-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.
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