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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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111In-Diethylenetriaminepentaacetic acid-Lys40-exendin-3

, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: November 3, 2010.

Chemical name:111In-Diethylenetriaminepentaacetic acid-Lys40-exendin-3
Abbreviated name:111In-DTPA-Lys40-exendin-3
Agent category:Peptide
Target:Glucagon-like peptide-1 receptor (GLP-1R)
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), gamma imaging
Source of signal:111In
  • Checkbox In vitro
  • Checkbox Rodents
Structure not available in PubChem.



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, and it inhibits gastric emptying, glucagon secretion, and glucose production (2). In addition, GLP-1 induces insulin release from β-cells in the pancreas. GLP-1 also induced proliferation of the pancreatic β-cells. The GLP-1 receptor (GLP-1R) has been identified in normal tissues such as the pancreas, 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. 111In-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 (5, 6). Exendin-3 and exendin-4 differ in two amino acids (positions 2 and 3), which are located in the region of the peptide that is responsible for internalization of the ligand-receptor complex. Brom et al. (7) investigated the usefulness of DTPA-Lys40-exendin-3 (111In-DTPA-Lys40-exendin-3) as a SPECT agent for imaging insulinomas.

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A mixture of 150 MBq (4.1 mCi) 111InCl3 and DTPA-Lys40-exendin-3 was incubated in buffer (pH 5.5) for 30 min at room temperature. 111In-DTPA-Lys40-exendin-3 was identified with high-performance liquid chromatography (HPLC). 111In-DTPA-Lys40-exendin-3 exhibited a radiochemical purity of >95% and a specific activity of 700 GBq/µmol (19 Ci/µmol) after HPLC purification.

In Vitro Studies: Testing in Cells and Tissues


Brom et al. (7) reported that natIn-DTPA-Lys40-exendin-3, natIn-DOTA-Lys40-exendin-3, and natGa-DOTA-Lys40-exendin-3 exhibited 50% inhibitory concentration (IC50) values of 8.5 nM, 5.3 nM, and 5.7 nM, respectively. The inhibition assays were performed with GLP-1R–expressing rat insulinoma INS-1 cells and 111In-DTPA-Lys40-exendin-3. 111In-DTPA-Lys40-exendin-3 (~55 fmol) was specifically accumulated into INS-1 cells in culture with 0.5 fmol at 0.5 h and 6.5 fmol at 4 h. Most of the accumulated radioactivity was internalized into the cells (60–80%). No blocking studies were reported.

Animal Studies



Brom et al. (7) performed biodistribution studies in nude mice (n = 5) bearing INS-1 insulinomas that consisted of injection of 0.37 MBq (10 μCi) 111In-DTPA-Lys40-exendin-3 or 111In-DTPA-Lys40-exendin-4. An experiment that consisted of coinjection of excess exendin-3 was also performed. Tumor accumulation was 36.0 ± 5.5% injected dose/gram (ID/g) and 36.3 ± 8.0% ID/g at 4 h after injection of 111In-DTPA-Lys40-exendin-3 or 111In-DTPA-Lys40-exendin-4, respectively. Excess exendin-3 reduced the tumor accumulation to the background level (~1% ID/g). Specific and moderate uptake was observed in the pancreas, stomach, and lung. Uptake in the kidneys was ~140% ID/g and was not displaced by exendin-3. Marginal accumulation (<1% ID/g) was observed in the muscle, blood, heart, spleen, and liver. As a comparison, tumor accumulation of 111In-DTPA-Lys40-exendin-3 and 111In-DTPA-Lys40-exendin-4 was more than two-fold higher than that of 68Ga-DOTA-Lys40-exendin-3.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.

NIH Support

1R01 AG030328-01


Theodorakis M.J., Carlson O., Michopoulos S., Doyle M.E., Juhaszova M., Petraki K., Egan J.M. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol Endocrinol Metab. 2006;290(3):E550–9. [PubMed: 16219666]
Doyle M.E., Egan J.M. Glucagon-like peptide-1. Recent Prog Horm Res. 2001;56:377–99. [PubMed: 11237222]
Reubi J.C., Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging. 2003;30(5):781–93. [PubMed: 12707737]
Meier J.J., Nauck M.A. Glucagon-like peptide 1(GLP-1) in biology and pathology. Diabetes Metab Res Rev. 2005;21(2):91–117. [PubMed: 15759282]
Gotthardt M., Lalyko G., van Eerd-Vismale J., Keil B., Schurrat T., Hower M., Laverman P., Behr T.M., Boerman O.C., Goke B., Behe M. A new technique for in vivo imaging of specific GLP-1 binding sites: First results in small rodents. Regul Pept. 2006;137(3):162–7. [PubMed: 16930741]
Wild D., Behe M., Wicki A., Storch D., Waser B., Gotthardt M., Keil B., Christofori G., Reubi J.C., Macke H.R. [Lys40(Ahx-DTPA-111In)NH2]Exendin-4, a Very Promising Ligand for Glucagon-like Peptide-1 (GLP-1) Receptor Targeting. J Nucl Med. 2006;47(12):2025–2033. [PubMed: 17138746]
Brom M., Oyen W.J., Joosten L., Gotthardt M., Boerman O.C. 68Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET. Eur J Nucl Med Mol Imaging. 2010;37(7):1345–55. [PMC free article: PMC2886138] [PubMed: 20111963]


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