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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/micad/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-micad-lrg.png" alt="Cover of Molecular Imaging and Contrast Agent Database (MICAD)" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>Molecular Imaging and Contrast Agent Database (MICAD) [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK92500_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK92500_dtls__"><div>Bethesda (MD): <a href="https://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>; 2004-2013.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/micad/">Contents</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/micad/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/micad/RNAHYNIC99mTc/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/Annexin-HYNIC-99mTc/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK92500_"><span class="title" itemprop="name"><sup>99m</sup>Tc-Hydrazinonicotinamide-aminohexanoic acid-Lys<sup>40</sup>-exendin-4</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">[Lys<sup>40</sup>(Ahx-HYNIC-<sup>99m</sup>Tc)NH<sub>2</sub>]-exendin-4</div><p class="contrib-group"><span itemprop="author">Kam Leung</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK92500_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK92500_ai__"><div class="contrib half_rhythm"><span itemprop="author">Kam Leung</span>, PhD<div class="affiliation small">National Center for Biotechnology Information, NLM, NIH, Bethesda, MD<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@DACIM" class="oemail">vog.hin.mln.ibcn@DACIM</a></div></div><div class="small">Corresponding author.</div></div></div><p class="small">Created: <span itemprop="datePublished">January 20, 2012</span>; Last Update: <span itemprop="dateModified">April 26, 2012</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="Exendin4HYNIC99mTc.T.nc_chemical_name99m" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92500/table/Exendin4HYNIC99mTc.T.nc_chemical_name99m/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Exendin4HYNIC99mTc.T.nc_chemical_name99m_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Chemical name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-Hydrazinonicotinamide-aminohexanoic acid-Lys<sup>40</sup>-exendin-4</td><td rowspan="9" colspan="1" style="text-align:center;vertical-align:middle;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Abbreviated name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">[Lys<sup>40</sup>(Ahx-HYNIC-<sup>99m</sup>Tc)NH<sub>2</sub>]-exendin-4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Synonym:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-HYNIC-Ahx-Lys<sup>40</sup>-exendin-4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Agent category:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Peptide</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Target:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Glucagon-like peptide-1 receptor (GLP-1R)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Target category:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Receptor</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Method of detection:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Single-photon emission computed tomography (SPECT), gamma planar imaging</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Source of signal:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Activation:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Studies:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul class="simple-list"><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" />
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<i>In vitro</i>
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</div></li><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
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</div></li></ul>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Click on <a href="/entrez/viewer.fcgi?db=protein&val=248418" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">protein</a>, <a href="/entrez/viewer.fcgi?db=nuccore&val=1916066" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">nucleotide</a> (RefSeq), and <a href="/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=14526" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">gene</a> for more information about exendin-4.</td></tr></tbody></table></div></div><div id="Exendin4HYNIC99mTc.Background"><h2 id="_Exendin4HYNIC99mTc_Background_">Background</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=Ahx%20Exendin-4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Glucagon-like peptide-1 (GLP-1, 30 amino acids) is secreted from enteroendocrine cells of the distal small intestine in response to food ingestion (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.1">1</a>). GLP-1 plays an important role in glucose metabolism and homeostasis. It inhibits gastric emptying, glucagon secretion, and glucose production (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.2">2</a>). In addition, it induces insulin release from the pancreatic β-cells as well as their proliferation. The GLP-1 receptor 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 (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.3">3</a>). In insulinomas, GLP-1 receptor density is considerably greater, and the GLP-1 receptor is more frequently observed than somatostatin receptors.</p><p>Exendin-4 is a GLP-1 analog with 39 amino acids isolated from the venom of the Gila monster (<i>Heloderma suspectum</i>) (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.4">4</a>). Exendin-4 and GLP-1 share a 53% amino acid sequence homology. Exendin-4 is a more potent and longer-lasting GLP-1 receptor agonist than GLP-1. Exendin-4 is resistant to cleavage by dipeptidyl peptidase IV, whereas the first two <i>N</i>-terminal amino acids of GLP-1 are rapidly cleaved. Exenatide, a synthetic version of exendin-4, is the first GLP-1 mimetic recently approved by the United States Food and Drug Administration (FDA) for use in select patients with type 2 diabetes (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.5">5</a>). <sup>99m</sup>Tc-Hydrazinonicotinamide-aminohexanoic acid-Lys<sup>40</sup>-exendin-4 ([Lys<sup>40</sup>(Ahx-HYNIC-<sup>99m</sup>Tc)NH<sub>2</sub>]-exendin-4) is being developed for single-photon emission computed tomography (SPECT) imaging of the GLP-1 receptor (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.6">6</a>).</p><div id="Exendin4HYNIC99mTc.Related_Resource_Link"><h3>Related Resource Links:</h3><ul><li class="half_rhythm"><div>Chapters in MICAD (<a href="/sites/entrez?Db=books&Cmd=DetailsSearch&Term=GLP-1%5BAll+Fields%5D+AND+micad%5Bbook%5D" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GLP-1</a>)</div></li><li class="half_rhythm"><div>Gene information in NCBI (<a href="/sites/entrez?Db=gene&Cmd=DetailsSearch&Term=2740" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GLP-1R</a>)</div></li><li class="half_rhythm"><div>Articles in Online Mendelian Inheritance in Man (OMIM) (<a href="http://omim.org/entry/138032" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GLP-1R</a>)</div></li><li class="half_rhythm"><div>Clinical trials (<a href="http://www.clinicaltrials.gov/ct2/results?term=GLP-1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Exendin</a>)</div></li><li class="half_rhythm"><div>Drug information in FDA (<a href="http://google2.fda.gov/search?q=exendin&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&output=xml_no_dtd&getfields=*&x=11&y=18" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Exendin</a>)</div></li></ul></div></div><div id="Exendin4HYNIC99mTc.Synthesis"><h2 id="_Exendin4HYNIC99mTc_Synthesis_">Synthesis</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=Ahx%20Exendin-4%20and%20synthesis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The structure and composition of [Lys<sup>40</sup>(Ahx-HYNIC)NH<sub>2</sub>]-exendin-4 was verified with high-performance liquid chromatography and matrix-assisted laser desorption-ionization mass spectrometry (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.6">6</a>). A mixture of EDDA and 370 MBq (10 mCi) <sup>99m</sup>TcO<sub>4</sub>− was added to a vial containing tricine, SnCl<sub>2</sub>, and [Lys<sup>40</sup>(Ahx-HYNIC)NH<sub>2</sub>]-exendin-4 (7.7 nmol) and incubated for 10 min at 95°C, with a 95% labeling yield of [Lys<sup>40</sup>(Ahx-HYNIC-<sup>99m</sup>Tc)NH<sub>2</sub>]-exendin-4 and a specific activity of 48 GBq/µmol (1.3 Ci/µmol). The stability of [Lys<sup>40</sup>(Ahx-HYNIC-<sup>99m</sup>Tc)NH<sub>2</sub>]-exendin-4 in solution was not reported.</p></div><div id="Exendin4HYNIC99mTc.In_Vitro_Studies_Test"><h2 id="_Exendin4HYNIC99mTc_In_Vitro_Studies_Test_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=Ahx%20Exendin-4%20and%20in%20vitro" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Wild et al. (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.6">6</a>) reported that [Lys<sup>40</sup>(Ahx-HYNIC-<sup>99m</sup>Tc)NH<sub>2</sub>]-exendin-4 was accumulated into β-cell tumors in culture with 1.50 ± 0.49% of incubation dose at 1 h and 6.50 ± 1.94% at 4 h. Most of the accumulated radioactivity was internalized into the cells (>80%).</p></div><div id="Exendin4HYNIC99mTc.Animal_Studies"><h2 id="_Exendin4HYNIC99mTc_Animal_Studies_">Animal Studies</h2><div id="Exendin4HYNIC99mTc.Rodents"><h3>Rodents</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=Ahx%20Exendin-4%20and%20rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Wild et al. (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.6">6</a>) performed <i>ex vivo</i> biodistribution studies with the use of Rip1Tag2 mice (<i>n</i> = 6/group) with spontaneous insulinoma β-cell tumors. The organ with the highest uptake was the tumor (93.1 ± 19.9% injected dose/g (% ID/g)), followed by the kidneys (60 ± 12% ID/g), lungs (16 ± 6% ID/g), pancreas (7.4 ± 2.2% ID/g), stomach (1.2 ± 0.3% ID/g), liver (0.7 ± 0.2% ID/g), and spleen (0.5 ± 0.2% ID/g) at 4 h after injection of [Lys<sup>40</sup>(Ahx-HYNIC-<sup>99m</sup>Tc)NH<sub>2</sub>]-exendin-4 (10 pmol/mouse). Excess unlabeled [Lys<sup>40</sup>(Ahx-HYNIC)NH<sub>2</sub>]-exendin-4 (5 nmol) blocked accumulation by >95% in the tumor and GLP-1R-expressing organs, such as the pancreas and lung, but there was little inhibition in the kidneys. Blood clearance was fast, with 0.4% ID/g remaining in the blood 4 h after injection. In contrast, the tumor washout rate was slow. The tumor/blood ratio was 29 at 0.5 h and 266 at 4 h. The tumor/muscle, tumor/pancreas, and tumor/kidney ratios were 547, 13, and 2 at 4 h, respectively.</p><p>Pinhole SPECT imaging of two Rip1Tag2 mice identified high uptake in the kidneys at 4 h after injection of 37 MBq (1 mCi) [Lys<sup>40</sup>(Ahx-HYNIC-<sup>99m</sup>Tc)NH<sub>2</sub>]-exendin-4 (<a class="bk_pop" href="#Exendin4HYNIC99mTc.REF.6">6</a>). SPECT images clearly identified four tumors (1.0–3.2 mm) in the pancreas in one of the mice. No blocking studies were reported.</p></div><div id="Exendin4HYNIC99mTc.Other_NonPrimate_Mamm"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=Ahx%20Exendin-4%20and%20%28dog%20or%20pig%20or%20sheep%20or%20rabbit%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="Exendin4HYNIC99mTc.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=Ahx%20Exendin-4%20and%20%28primate%20not%20human%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="Exendin4HYNIC99mTc.Human_Studies"><h2 id="_Exendin4HYNIC99mTc_Human_Studies_">Human Studies</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=Ahx%20Exendin-4%20and%20human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="Exendin4HYNIC99mTc.References"><h2 id="_Exendin4HYNIC99mTc_References_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="Exendin4HYNIC99mTc.REF.1">Theodorakis M.J., Carlson O., Michopoulos S., Doyle M.E., Juhaszova M., Petraki K., Egan J.M.
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<em>Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP.</em>
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<span><span class="ref-journal">Am J Physiol Endocrinol Metab. </span>2006;<span class="ref-vol">290</span>(3):E550–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16219666" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16219666</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="Exendin4HYNIC99mTc.REF.2">Doyle M.E., Egan J.M.
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<em>Glucagon-like peptide-1.</em>
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<span><span class="ref-journal">Recent Prog Horm Res. </span>2001;<span class="ref-vol">56</span>:377–99.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11237222" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11237222</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="Exendin4HYNIC99mTc.REF.3">Reubi J.C., Waser B.
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<em>Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting.</em>
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<span><span class="ref-journal">Eur J Nucl Med Mol Imaging. </span>2003;<span class="ref-vol">30</span>(5):781–93.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12707737" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12707737</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="Exendin4HYNIC99mTc.REF.4">Meier J.J., Nauck M.A.
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<em>Glucagon-like peptide 1(GLP-1) in biology and pathology.</em>
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<span><span class="ref-journal">Diabetes Metab Res Rev. </span>2005;<span class="ref-vol">21</span>(2):91–117.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15759282" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15759282</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="Exendin4HYNIC99mTc.REF.5">Nielsen L.L., Young A.A., Parkes D.G.
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<em>Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes.</em>
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<span><span class="ref-journal">Regul Pept. </span>2004;<span class="ref-vol">117</span>(2):77–88.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14700743" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14700743</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="Exendin4HYNIC99mTc.REF.6">Wild D., Wicki A., Mansi R., Behe M., Keil B., Bernhardt P., Christofori G., Ell P.J., Macke H.R.
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<em>Exendin-4-based radiopharmaceuticals for glucagonlike peptide-1 receptor PET/CT and SPECT/CT.</em>
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<span><span class="ref-journal">J Nucl Med. </span>2010;<span class="ref-vol">51</span>(7):1059–67.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20595511" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20595511</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK92500/?report=reader">PubReader</a></li><li><a href="/books/NBK92500/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK92500" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK92500" style="display:none" title="Cite this Page"><div class="bk_tt">Leung K. 99mTc-Hydrazinonicotinamide-aminohexanoic acid-Lys40-exendin-4. 2012 Jan 20 [Updated 2012 Apr 26]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK92500/pdf/Bookshelf_NBK92500.pdf">PDF version of this page</a> (130K)</li><li><a href="/books/n/micad/toc/bin/micad.csv">MICAD summary (CSV file)</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#Exendin4HYNIC99mTc.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#Exendin4HYNIC99mTc.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#Exendin4HYNIC99mTc.In_Vitro_Studies_Test" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#Exendin4HYNIC99mTc.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#Exendin4HYNIC99mTc.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#Exendin4HYNIC99mTc.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Search MICAD</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-application" id="Shutter"></a></div><div class="portlet_content"><form xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" name="frmSearch" method="get" action="/books/NBK5330/" id="frmSearch"><script type="text/javascript" src="/corehtml/pmc//js/bookshelf/micad.js">/**/</script><label class="offscreen_noflow" for="txtfield">Search term</label><input id="txtfield" type="text" name="f1_term" size="22" onKeyPress="KeyPress('micad',event,'/books/NBK5330/','')" /><button name="f1_search" type="submit">Go</button><button onclick="this.form.reset();" type="reset">Clear</button><p><b>Limit my Search:</b></p><div class="clearfix"><label for="detection">Method of detection:</label><div class="right"><select name="detection" id="detection" style="width:200px"><option value="" selected="selected">Any</option><option value="(MRI OR "Magnetic resonance imaging" OR MRS)">MRI</option><option value="Multimodal">Multimodal imaging</option><option value="Optical">Optical imaging</option><option value="PET">PET</option><option value="Photoacoustic">Photoacoustic imaging</option><option value="(SPECT OR planar)">SPECT</option><option value="Ultrasound">Ultrasound</option><option value="(x-ray OR ct)">X-ray, CT</option></select></div></div><div class="clearfix"><label for="signal">Source of signal/contrast:</label><div class="right"><select name="signal" id="signal" style="width:200px"><option value="" selected="selected">Any</option><optgroup label="MRI agents"><option value="(Copper OR Cu)">Copper</option><option value="(Europium OR Eu3+)">Europium</option><option value="(Fluorine OR 19F)">Fluorine</option><option value="(Gadolinium OR Gd3+)">Gadolinium</option><option value=""Hyperpolarized 13C"">Hyperpolarized 13C</option><option value=""Iron oxide"">Iron oxide</option><option value=""Nitroxide radicals"">Nitroxide radicals</option><option value="(Oxygen OR 17O)">Oxygen</option><option value="Thulium">Thulium</option></optgroup><optgroup label="Multimodal agents"><option value="((Gadolinium OR Gd3+) AND Optical)">Gadolinium and optical</option><option value="((Gadolinium OR Gd3+) AND (Gold OR Au))">Gadolinium and Gold</option><option value="("Iron oxide" AND (64Cu OR 124I OR 111In))">Iron oxide and
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value="(nanoparticle OR nanoparticles OR nanotubes OR "iron oxide")">Nanoparticles</option><option value="(siRNA OR "nucleic acid" OR oligonucleotide)">Nucleic acids</option><option value="peptide">Peptides</option><option value="polyeptide">Polyeptides</option><option value="(protein OR albumin OR chemokin OR immunoprotein OR luciferase OR albumin)">Proteins</option><option value="(virus OR adenovirus)">Viruses</option></select></div></div><div class="clearfix"><label for="target">Target Category:</label><div class="right"><select name="target" id="target" style="width:200px"><option value="" selected="selected">Any</option><option value="acceptor">Acceptors</option><option value=""adhesion molecule"">Adhesion molecules</option><option value="(antigen OR antibody-antigen)">Antigens</option><option value="(enzyme OR enzymes OR enzyme-substrate)">Enzymes</option><option value="(lipids OR lipophilic cation)">Lipids</option><option value="(receptor OR receptors OR receptor-ligand OR 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