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In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent.

In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent.

Authors :
Brand C
Abdel-Atti D
Zhang Y
Carlin S
Clardy SM
Keliher EJ
Weber WA
Lewis JS
Reiner T
Source :
Bioconjugate chemistry [Bioconjug Chem] 2014 Jul 16; Vol. 25 (7), pp. 1323-30. Date of Electronic Publication: 2014 Jun 13.
Publication Year :
2014

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 (64)Cu radiolabeling and copper-catalyzed click-conjugation. The bimodal imaging agent (64)Cu-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.

Details

Language :
English
ISSN :
1520-4812
Volume :
25
Issue :
7
Database :
MEDLINE
Journal :
Bioconjugate chemistry
Publication Type :
Academic Journal
Accession number :
24856928
Full Text :
https://doi.org/10.1021/bc500178d