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VivoTag-S 750-(S)-2-amino-4-pentynoic acid12-exendin-4.


Leung K1.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2011 Nov 01 [updated 2012 Jan 05].

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National Center for Biotechnology Information, NLM, NIH, Bethesda, MD


Glucagon-like peptide-1 (GLP-1; 30 amino acids) is secreted from enteroendocrine cells of the distal small intestine in response to food ingestion (1). GLP-1 plays an important role in glucose metabolism and homeostasis by inhibiting gastric emptying, glucagon secretion, and glucose production (2). In addition, GLP-1 induces insulin release from the pancreatic β-cells as well as their proliferation. The GLP-1 receptor (GLP-1R) has been identified in normal tissues such as the pancreatic β-cells, stomach, brain, and lung, and it has been shown to be highly overexpressed in human insulinomas and gastrinomas (3). In insulinomas, GLP-1R density is considerably greater, and the GLP-1R is more frequently observed than somatostatin receptors. Exendin-4 is a GLP-1 analog with 39 amino acids isolated from the venom of the Gila monster (Heloderma suspectum) (4). Exendin-4 and GLP-1 share a 53% amino acid sequence homology. Exendin-4 is a more potent and longer-lasting GLP-1R agonist than GLP-1. Exendin-4 is resistant to cleavage by dipeptidyl peptidase IV, whereas the first two N-terminal amino acids of GLP-1 are rapidly cleaved. Exenatide, a synthetic version of exendin-4, is the first GLP-1 mimetic approved by the United States Food and Drug Administration (FDA) for use in select patients with type 2 diabetes (5). 111In-Labeled diethylenetriamine pentaacetic acid-aminohexanoic acid-Lys40-exendin-4 (111In-DTPA-Ahx-Lys40-exendin-4) has been developed for single-photon emission computed tomography (SPECT) imaging of the GLP-1R (6). For optical near-infrared (NIR) fluorescence imaging, Reiner et al. (7) replaced the Lys at position 12 of exendin-4 with the non-natural amino acid (S)-2-amino-4-pentynoic acid to form a neopeptide, E4X12. The azide-functionalized NIR dye VivoTag-S 750 (VT750) was conjugated to the non-natural amino acid at position 12 via azide-alkyne cycoaddition to form VT750-(S)-2-amino-4-pentynoic acid12-exendin-4 (E4X12-VT750). E4X12-VT750 has been evaluated as an optical imaging agent for GLP-1R density and β-cell mass (BCM) in normal mice and in mice treated with streptozotocin (STZ) to induce BCM loss and diabetes.

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