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J Nucl Med. 2013; 54 (Supplement 2):384
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Molecular Targeting Probes - Radioactive and Nonradioactive

Preclinical Probes: Cardiovascular, Endocrine, and Other

SPECT imaging of GLP-1R for the assessment of beta cell mass (BCM) change in a diabetic mouse model

Su-Tang Lo1, Patrick Thomas1, Jung-Mo Ahn2, Orhan Oz1 and Xiankai Sun3

1 Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 2 Department of Chemistry, University of Texas Dallas, Dallas, TX 3 Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX

Abstract No. 384

Objectives: A reliable, non-invasive method for quantification of the pancreatic BCM in vivo would give further insight into the pathophysiology of diabetes. Glucagon-like Peptide-1 Receptor (GLP-1R) has been reported to be specifically expressed in pancreatic β-cells and could be a biomarker for monitoring pancreatic β-cell mass (BCM) changes. To verify this hypothesis, we investigated the potential of SPECT imaging using a 67Ga-labeled GLP-1 analog to evaluate the BCM change in vivo.

Methods: A SPECT tracer was developed by conjugation of the GLP-1 analog, EM2198, with bifunctional chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for radiolabeling with 67Ga. Normal and Streptozotocin (STZ)-treated mice were used for the imaging. Prior to SPECT/CT imaging, oral BaSO4 CT contrast was given by gavage and L-Lysine was intraperitoneally injected to enhance the visibility of gastrointestinal tract and reduce the renal uptake of peptide-based imaging probe, respectively. These procedures aid the localization of the pancreas area. For SPECT imaging, 400 µCi dose of 67Ga-NOTA-EM2198 was injected via the tail-vein. After imaging, ex vivo SPECT scans and histological examination were performed to verify the in vivo imaging finding.

Results: The pancreas area could be clearly identified on the SPECT images with the aid of BaSO4-enhanced CT. The standardized uptake value (SUV) of 67Ga-NOTA-EM2198 in the pancreas was significantly higher in normal mice than in the STZ-treated mice (normal: 0.65±0.08 g/ml; STZ-treated: 0.29±0.02 g/ml; n=3, p=0.0016). Ex vivo PET imaging of excised organs of interest confirmed the in vivo results, which were further verified by immunohistological assay of GLP-1R expression in the pancreatic β-cells.

Conclusions: A 67Ga-labeled GLP-1 analog, 67Ga-NOTA-EM2198 was successfully developed with potential to monitor the BCM change noninvasively by SPECT.





This Article
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Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Lo, S.-T.
Right arrow Articles by Sun, X.
PubMed
Right arrow Articles by Lo, S.-T.
Right arrow Articles by Sun, X.