Back to Search
Start Over
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.
- 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.
- Subjects :
- Adenoma, Islet Cell diagnostic imaging
Adenoma, Islet Cell drug therapy
Amino Acid Sequence
Animals
Cell Tracking methods
Cells, Cultured
Exenatide
Female
Fluorescent Antibody Technique
Glucagon-Like Peptide-1 Receptor
Humans
Hypoglycemic Agents administration & dosage
Mice
Mice, Nude
Molecular Sequence Data
Pancreas diagnostic imaging
Pancreas drug effects
Peptides administration & dosage
Receptors, Glucagon analysis
Venoms administration & dosage
Xenograft Model Antitumor Assays
Adenoma, Islet Cell metabolism
Copper Radioisotopes
Multimodal Imaging methods
Optical Imaging methods
Pancreas metabolism
Positron-Emission Tomography methods
Radiopharmaceuticals
Receptors, Glucagon metabolism
Subjects
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