In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent Journal Article
| Authors: | Brand, C.; Abdel-Atti, D.; Zhang, Y.; Carlin, S.; Clardy, S. M.; Keliher, E. J.; Weber, W. A.; Lewis, J. S.; Reiner, T. |
| Article Title: | In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent |
| Abstract: | Accurate visualization and quantification of β-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 μCi/μg, >98% radiochemical purity). The agent showed good performance in vivo and ex vivo, visualizing small xenografts (<2 mm) with PET and pancreatic β-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. © 2014 American Chemical Society. |
| Journal Title: | Bioconjugate Chemistry |
| Volume: | 25 |
| Issue: | 7 |
| ISSN: | 1043-1802 |
| Publisher: | American Chemical Society |
| Date Published: | 2014-07-16 |
| Start Page: | 1323 |
| End Page: | 1330 |
| Language: | English |
| DOI: | 10.1021/bc500178d |
| PROVIDER: | scopus |
| PUBMED: | 24856928 |
| PMCID: | PMC4215873 |
| DOI/URL: | |
| Notes: | Export Date: 1 August 2014 -- CODEN: BCCHE -- Source: Scopus |
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