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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="#__NBK23297_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK23297_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/CCMSH99mTc/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/Folate-DO3A-EA99mTc/" 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="_NBK23297_"><span class="title" itemprop="name"><sup>99m</sup>Tc-[Cys<sup>3,4,10</sup>,<span class="small-caps">d</span>-Phe<sup>7</sup>,Arg<sup>11</sup>]α-MSH<sub>3-13</sub></span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"><sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH</div><p class="contrib-group"><span itemprop="author">Kenneth T Cheng</span>, PhD and <span itemprop="author">Thomas P Quinn</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK23297_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK23297_ai__"><div class="contrib half_rhythm"><span itemprop="author">Kenneth T Cheng</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><div class="contrib half_rhythm"><span itemprop="author">Thomas P Quinn</span>, PhD<div class="affiliation small">Department of Biochemistry, University of Missouri-Columbia, Columbia, MO, Corresponding Author<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.iruossim@tnniuq" class="oemail">ude.iruossim@tnniuq</a></div></div><div class="small">Corresponding author.</div></div></div><p class="small">Created: <span itemprop="datePublished">January 26, 2007</span>; Last Update: <span itemprop="dateModified">January 22, 2008</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="MSH99mTc.T.nc_chemical_name99mtccys3410d" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK23297/table/MSH99mTc.T.nc_chemical_name99mtccys3410d/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__MSH99mTc.T.nc_chemical_name99mtccys3410d_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-[Cys<sup>3,4,10</sup>,<span class="small-caps">d</span>-Phe<sup>7</sup>,Arg<sup>11</sup>]α-MSH<sub>3-13</sub></td><td rowspan="9" colspan="1" style="text-align:center;vertical-align:middle;">
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<span class="graphic"><img src="/books/NBK23297/bin/MSH99mTc.jpg" alt="Image MSH99mTc.jpg" /></span>
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</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;"><sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH</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-α-MSH, <sup>99m</sup>Tc-Labeled α-melanocyte−stimulating hormone peptides</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Backbone:</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;">Melanocortin-1 (MC-1) receptor</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Mechanism:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Peptide-receptor binding</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) or 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;"><sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH structure.<br />Click on <a href="/entrez/viewer.fcgi?db=protein&val=27477129" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">protein</a>, <a href="/entrez/viewer.fcgi?db=nucleotide&val=27477128" 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=4157" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">gene</a> for more information about the melanocortin-1 receptor.</td></tr></tbody></table></div></div><div id="MSH99mTc.Background"><h2 id="_MSH99mTc_Background_">Background</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%2899mTc-%20and%20111In-labeled%20alpha-melanocyte-stimulating%20hormone%20peptides%29%20OR%20%28radiolabeled-alpha-MSH%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p><sup>99m</sup>Tc-[Cys<sup>3,4,10</sup>,<span class="small-caps">d</span>-Phe<sup>7</sup>,Arg<sup>11</sup>]αMSH<sub>3-13</sub> (<sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH) is a radioligand developed as a single-photon emission computed tomography (SPECT) imaging probe for primary and metastatic melanoma (<a class="bk_pop" href="#MSH99mTc.REF.1">1</a>). <sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH is an α-melanocyte−stimulating hormone (MSH) peptide labeled with <sup>99m</sup>Tc, a gamma emitter with a physical <i>t</i><sub>½</sub> of 6 h.</p><p>Malignant melanoma is the sixth most common cancer in the United States (<a class="bk_pop" href="#MSH99mTc.REF.1">1</a>). Early diagnosis and prompt surgical removal comprise the best approach for a possible cure (<a class="bk_pop" href="#MSH99mTc.REF.2">2</a>). The melanocortin (MC) system is the best characterized neuropeptide network of the skin, and it is involved in pigmentation regulation, cortisol production and many other physiological processes (<a class="bk_pop" href="#MSH99mTc.REF.3">3</a>). Most cutaneous cell types express MC receptors, proopiomelanocortin (POMC), prohormone convertases, and also release MCs. Five MC receptors (MC-1 to MC-5) have been cloned and characterized as receptors that belong to the G-protein−coupled receptors superfamily. MSHs (α-, β-, and γ-MSH) are derived from POMC by the proteolytic action of prohormone convertases. α-MSH (Ac-Ser<sup>1</sup>-Tyr<sup>2</sup>-Ser<sup>3</sup>-Met<sup>4</sup>-Glu<sup>5</sup>-His<sup>6</sup>-Phe<sup>7</sup>-Arg<sup>8</sup>-Trp<sup>9</sup>-Gly<sup>10</sup>-Lys<sup>11</sup>-Pro<sup>12</sup>-Val<sup>13</sup>-NH<sub>2</sub>) is a 13−amino acid peptide and is the most potent naturally occurring melanotropic peptide (<a class="bk_pop" href="#MSH99mTc.REF.4">4</a>). The biological effects of α-MSH are mediated <i>via</i> MC receptors.</p><p>Although positron emission tomography (PET) imaging with [<sup>18</sup>F]fluoro-2-deoxy-2-<span class="small-caps">d</span>-glucose ([<sup>18</sup>F]FDG) is effective in the detection of melanoma, it is not melanoma-specific and some melanoma cells do not take up [<sup>18</sup>F]FDG (<a class="bk_pop" href="#MSH99mTc.REF.5" data-bk-pop-others="MSH99mTc.REF.6">5, 6</a>). Radiolabeled α-MSH peptide analogs have been shown to specifically bind to MC-1 receptors which are overexpressed on human and mouse melanoma cells (<a class="bk_pop" href="#MSH99mTc.REF.5" data-bk-pop-others="MSH99mTc.REF.7 MSH99mTc.REF.8 MSH99mTc.REF.9 MSH99mTc.REF.10">5, 7-10</a>). Some studies have successfully used 1,4,7,10-tetraazacyclodecane-<i>N</i>,<i>N'</i>,<i>N''</i>,<i>N'''</i>-tetraacetic acid (DOTA) coupled to the α-MSH peptide analogs for radiolabeling. These α-MSH derivatives (DOTA-α-MSH) can be labeled with a variety of radionuclides (<a class="bk_pop" href="#MSH99mTc.REF.5">5</a>). To improve the <i>in vivo</i> pharmacokinetics of these radiolabeled peptides, a number of different α-MSH analogs have been designed (<a class="bk_pop" href="#MSH99mTc.REF.11" data-bk-pop-others="MSH99mTc.REF.12">11, 12</a>). Froidevaux et al. (<a class="bk_pop" href="#MSH99mTc.REF.11">11</a>) showed that the kidney uptake of a short linear DOTA−α-MSH analog (DOTA-NAPamide) could be considerably reduced by neutralizing the charge of the Lys<sup>11</sup> residue. Giblin et al. (<a class="bk_pop" href="#MSH99mTc.REF.13">13</a>) used metal cyclization to design a new class of α-MSH peptide analogs that are resistant to chemical and proteolytic degradation <i>in vivo</i> (<a class="bk_pop" href="#MSH99mTc.REF.10">10</a>). <sup>99m</sup>Tc-CCMSH analogs, cyclized through site-specific coordination of <sup>99m</sup>TcO, showed excellent tumor uptake and retention properties in B16/F1 murine melanoma-bearing C57 mice (<a class="bk_pop" href="#MSH99mTc.REF.13" data-bk-pop-others="MSH99mTc.REF.14">13, 14</a>). Miao et al. (<a class="bk_pop" href="#MSH99mTc.REF.12">12</a>) replaced the Lys<sup>11</sup> with Arg<sup>11</sup> in the CCMSH analog to form (Arg<sup>11</sup>)CCMSH in an effort to reduce nonspecific kidney uptake and minimize the kidney radiation dose.</p></div><div id="MSH99mTc.Synthesis"><h2 id="_MSH99mTc_Synthesis_">Synthesis</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%2899mTc-%20and%20111In-labeled%20alpha-melanocyte-stimulating%20hormone%20peptides%29%20OR%20%28radiolabeled-alpha-MSH%29%20AND%20synthesis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Miao et al. (<a class="bk_pop" href="#MSH99mTc.REF.12">12</a>) reported the synthesis of the (Arg<sup>11</sup>)CCMSH by using the standard fluorenylmethoxycarbonyl (Fmoc)/HBTU chemistry on amide resin. A solid-phase peptide synthesizer was used. The peptide was acetylated with glacial acetic acid at the N-terminus. The peptide was deprotected and cleaved from the resin by a mixture of trifluoroacetic acid, thioanisol, ethanedithiol, and water at room temperature for 3 h. The peptide was then purified by high-performance liquid chromatography (HPLC), and the identity was confirmed by electrospray ionization mass spectrometry. The <sup>99m</sup>Tc radiolabeling was prepared <i>via</i> a glucoheptonate transchelation reaction (<a class="bk_pop" href="#MSH99mTc.REF.14">14</a>).In this procedure, stannous chloride (SnCl<sub>2</sub>) was used as a reducing agent and glucoheptonate was used as a transfer ligand. Briefly, 10 μg of the peptide was added to the mixture of SnCl<sub>2</sub>, <sup>99m</sup>Tc-pertechnetate, and glucoheptonate. The mixture was incubated at 75ºC for 30 min. The final <sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH product was purified by HPLC. The specific activity was 1.2135 x 10<sup>10</sup> MBq/g (3.280 x 10<sup>8</sup> mCi/g). Based on a molecular weight of 1,467, the specific activity can be estimated to be 1.79 x 10<sup>7</sup> MBq/μmol (48.4 x 10<sup>4</sup> mCi/μmol).The radiochemical stability was evaluated in phosphate- buffered saline (pH 7.4). Over a 24-h period of incubation at 25ºC in phosphate-buffered saline, only radiolabeled peptide was detected by HPLC analysis with no detectable free radioactivity (<a class="bk_pop" href="#MSH99mTc.REF.14">14</a>).</p></div><div id="MSH99mTc.In_Vitro_Studies_Testing_in_Cel"><h2 id="_MSH99mTc_In_Vitro_Studies_Testing_in_Cel_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-%20and%20111In-labeled%20alpha-melanocyte-stimulating%20hormone%20peptides%29%20OR%20%28radiolabeled-alpha-MSH%29%29%20AND%20in%20vitro" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Giblin et al. (<a class="bk_pop" href="#MSH99mTc.REF.13">13</a>) performed <i>in vitro</i> quantitative receptor-binding assays of unlabeled CCMSH on B16/F1 murine melanoma cells. The inhibition constant (IC<sub>50</sub>) was determined to be 7.6 x 10−<sup>9</sup> M. Miao et al. (<a class="bk_pop" href="#MSH99mTc.REF.12">12</a>) determined the IC<sub>50</sub> of unlabeled (Arg<sup>11</sup>)CCMSH to be 1.7 X 10−<sup>9</sup> M, and the molecular weight was measured to be 1,476.</p></div><div id="MSH99mTc.Animal_Studies"><h2 id="_MSH99mTc_Animal_Studies_">Animal Studies</h2><div id="MSH99mTc.Rodents"><h3>Rodents</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-%20and%20111In-labeled%20alpha-melanocyte-stimulating%20hormone%20peptides%29%20OR%20%28radiolabeled-alpha-MSH%29%29%20AND%20rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Biodistribution and SPECT imaging studies with <sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH were conducted in C57 mice bearing B16/F1 (flank melanoma tumors) and B16/F10 (pulmonary metastatic melanoma tumors) melanomas (<a class="bk_pop" href="#MSH99mTc.REF.1">1</a>). Each mouse received 27.75 MBq (0.75 mCi) of <sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH by i.v. administration. The radioactivity levels in the flank tumors (<i>n</i> = 4) were 14.03 ± 2.58 (1 h), 11.16 ± 1.77 (4 h), and 3.33 ± 0.50 (24 h) % injected dose per g (% ID/g). The tumor/muscle ratios were 61 (1 h), 372 (4 h), and 333 (24 h). The critical organ appeared to be the kidneys (% ID/g) with 11.66 ± 1.44 (1 h), 5.53 ± 1.17 (4 h), and 0.60 ± 0.08 (24 h). The other major organ radioactivity levels (% ID/g) at 1 h were 7.32 ± 1.28 (intestines), 3.00 ± 0.45 (stomach), 1.59 ± 0.19 (liver), 1.52 ± 0.39 (lung), 1.97 ± 0.37 (skin), 0.63 ± 0.17 (heart), 0.04 ± 0.02 (brain), 0.23 ± 0.06 (muscle), and 0.87 ± 0.12 (blood). With coinjection of 10 μg of a high- affinity unlabeled αMSH analog, NDP ([NIe<sup>4</sup>,<span class="small-caps">d</span>-Phe<sup>7</sup>] αMSH), the tumor radioactivity was reduced by 90% (1.44 ± 0.23% ID/g) at 1 h.</p><p>In the pulmonary metastatic tumor model, the radioactivity levels (% ID/g) of <sup>99m</sup>Tc-(Arg<sup>11</sup>)CCMSH in the lung metastases (<i>n</i> = 4) were 2.77 ± 0.98 (2 h) and 2.30 ± 1.78 (4 h) (<a class="bk_pop" href="#MSH99mTc.REF.1">1</a>). The radioactivity levels in the normal lung were 0.52 ± 0.22 (2 h) and 0.65 ± 0.13 (4 h). The lung metastases/normal lung ratios were 5.33 and 3.54 at 2 h and 4 h, respectively. The lung metastases/muscle ratios were 11.54 and 5.00 at 2 h and 4 h, respectively. In the imaging studies, the flank melanoma tumors were visualized clearly at 2 h. The pulmonary metastatic melanoma lesions were also clearly imaged at 2 h, and distinct metastatic focal deposits were visible.</p></div><div id="MSH99mTc.Other_NonPrimate_Mammals"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-%20and%20111In-labeled%20alpha-melanocyte-stimulating%20hormone%20peptides%29%20AND%20%28dog%20OR%20rabbit%20OR%20pig%20OR%20sheep%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="MSH99mTc.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-%20and%20111In-labeled%20alpha-melanocyte-stimulating%20hormone%20peptides%29%20OR%20%28radiolabeled-alpha-MSH%29%29%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="MSH99mTc.Human_Studies"><h2 id="_MSH99mTc_Human_Studies_">Human Studies</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-%20and%20111In-labeled%20alpha-melanocyte-stimulating%20hormone%20peptides%29%20OR%20%28radiolabeled-alpha-MSH%29%29%20AND%20human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="MSH99mTc.Supplemental_Information"><h2 id="_MSH99mTc_Supplemental_Information_">Supplemental Information</h2><p>[<a href="/books/n/micad/disclaimer/">Disclaimers</a>]</p></div><div id="MSH99mTc.NIH_Support"><h2 id="_MSH99mTc_NIH_Support_">NIH Support</h2><p>NCI P50-CA-103130</p></div><div id="MSH99mTc.References"><h2 id="_MSH99mTc_References_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.1">Miao Y., Benwell K., Quinn T.P.
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<em>99mTc- and 111In-labeled alpha-melanocyte-stimulating hormone peptides as imaging probes for primary and pulmonary metastatic melanoma detection.</em>
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||
<span><span class="ref-journal">J Nucl Med. </span>2007;<span class="ref-vol">48</span>(1):73–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17204701" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17204701</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.2">Miao Y., Hylarides M., Fisher D.R., Shelton T., Moore H., Wester D.W., Fritzberg A.R., Winkelmann C.T., Hoffman T., Quinn T.P.
|
||
<em>Melanoma therapy via peptide-targeted {alpha}-radiation.</em>
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||
<span><span class="ref-journal">Clin Cancer Res. </span>2005;<span class="ref-vol">11</span>(15):5616–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16061880" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16061880</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.3">Bohm M., Luger T.A., Tobin D.J., Garcia-Borron J.C.
|
||
<em>Melanocortin receptor ligands: new horizons for skin biology and clinical dermatology.</em>
|
||
<span><span class="ref-journal">J Invest Dermatol. </span>2006;<span class="ref-vol">126</span>(9):1966–75.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16912693" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16912693</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.4">Catania A., Airaghi L., Garofalo L., Cutuli M., Lipton J.M.
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||
<em>The neuropeptide alpha-MSH in HIV infection and other disorders in humans.</em>
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||
<span><span class="ref-journal">Ann N Y Acad Sci. </span>1998;<span class="ref-vol">840</span>:848–56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9629310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9629310</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.5">Weiner R.E., Thakur M.L.
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<em>Radiolabeled peptides in oncology: role in diagnosis and treatment.</em>
|
||
<span><span class="ref-journal">BioDrugs. </span>2005;<span class="ref-vol">19</span>(3):145–63.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15984900" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15984900</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.6">Dimitrakopoulou-Strauss A., Strauss L.G., Burger C.
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||
<em>Quantitative PET studies in pretreated melanoma patients: a comparison of 6-[18F]fluoro-L-dopa with 18F-FDG and (15)O-water using compartment and noncompartment analysis.</em>
|
||
<span><span class="ref-journal">J Nucl Med. </span>2001;<span class="ref-vol">42</span>(2):248–56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11216523" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11216523</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.7">Tatro J.B., Reichlin S.
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||
<em>Specific receptors for alpha-melanocyte-stimulating hormone are widely distributed in tissues of rodents.</em>
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||
<span><span class="ref-journal">Endocrinology. </span>1987;<span class="ref-vol">121</span>(5):1900–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2822378" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2822378</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.8">Siegrist W., Solca F., Stutz S., Giuffre L., Carrel S., Girard J., Eberle A.N.
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||
<em>Characterization of receptors for alpha-melanocyte-stimulating hormone on human melanoma cells.</em>
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||
<span><span class="ref-journal">Cancer Res. </span>1989;<span class="ref-vol">49</span>(22):6352–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2804981" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2804981</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.9">Miao Y., Whitener D., Feng W., Owen N.K., Chen J., Quinn T.P.
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||
<em>Evaluation of the human melanoma targeting properties of radiolabeled alpha-melanocyte stimulating hormone peptide analogues.</em>
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<span><span class="ref-journal">Bioconjug Chem. </span>2003;<span class="ref-vol">14</span>(6):1177–84.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14624632" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14624632</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.10">Chen J., Cheng Z., Owen N.K., Hoffman T.J., Miao Y., Jurisson S.S., Quinn T.P.
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<em>Evaluation of an (111)In-DOTA-rhenium cyclized alpha-MSH analog: a novel cyclic-peptide analog with improved tumor-targeting properties.</em>
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<span><span class="ref-journal">J Nucl Med. </span>2001;<span class="ref-vol">42</span>(12):1847–55.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11752084" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11752084</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.11">Froidevaux S., Calame-Christe M., Tanner H., Eberle A.N.
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<em>Melanoma targeting with DOTA-alpha-melanocyte-stimulating hormone analogs: structural parameters affecting tumor uptake and kidney uptake.</em>
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||
<span><span class="ref-journal">J Nucl Med. </span>2005;<span class="ref-vol">46</span>(5):887–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15872364" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15872364</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.12">Miao Y., Owen N.K., Whitener D., Gallazzi F., Hoffman T.J., Quinn T.P.
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<em>In vivo evaluation of 188Re-labeled alpha-melanocyte stimulating hormone peptide analogs for melanoma therapy.</em>
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||
<span><span class="ref-journal">Int J Cancer. </span>2002;<span class="ref-vol">101</span>(5):480–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12216078" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12216078</span></a>]</div></dd><dt>13.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.13">Giblin M.F., Wang N., Hoffman T.J., Jurisson S.S., Quinn T.P.
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<em>Design and characterization of alpha-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination.</em>
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<span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>1998;<span class="ref-vol">95</span>(22):12814–8.</span> [<a href="/pmc/articles/PMC23606/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC23606</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9788997" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9788997</span></a>]</div></dd><dt>14.</dt><dd><div class="bk_ref" id="MSH99mTc.REF.14">Chen J., Cheng Z., Hoffman T.J., Jurisson S.S., Quinn T.P.
|
||
<em>Melanoma-targeting properties of (99m)technetium-labeled cyclic alpha-melanocyte-stimulating hormone peptide analogues.</em>
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||
<span><span class="ref-journal">Cancer Res. </span>2000;<span class="ref-vol">60</span>(20):5649–58.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11059756" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11059756</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
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<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div><div class="small"><span class="label">Bookshelf ID: NBK23297</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/20641499" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">20641499</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/micad/">Contents</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/micad/CCMSH99mTc/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/Folate-DO3A-EA99mTc/" title="Next page in this title">Next ></a></div></div></div></div>
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<div id="ncbi_share_book"><a href="#" class="ncbi_share" data-ncbi_share_config="popup:false,shorten:true" ref="id=NBK23297&db=books">Share</a></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/NBK23297/?report=reader">PubReader</a></li><li><a href="/books/NBK23297/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK23297" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK23297" style="display:none" title="Cite this Page"><div class="bk_tt">Cheng KT, Quinn TP. 99mTc-[Cys3,4,10,d-Phe7,Arg11]α-MSH3-13. 2007 Jan 26 [Updated 2008 Jan 22]. 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/NBK23297/pdf/Bookshelf_NBK23297.pdf">PDF version of this page</a> (402K)</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="#MSH99mTc.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#MSH99mTc.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#MSH99mTc.In_Vitro_Studies_Testing_in_Cel" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#MSH99mTc.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#MSH99mTc.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#MSH99mTc.Supplemental_Information" ref="log$=inpage&link_id=inpage">Supplemental Information</a></li><li><a href="#MSH99mTc.NIH_Support" ref="log$=inpage&link_id=inpage">NIH Support</a></li><li><a href="#MSH99mTc.References" ref="log$=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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radionuclides</option><option value="(Perfluorocarbon AND (Europium OR Eu3+))">Perfluorocarbon and
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europium</option><option value="(166Ho OR 67Ga OR 68Ga OR 123I OR 124I OR 125I)">Radionuclides</option></optgroup><optgroup label="Optical agents"><option value="("Fluorescent dyes" OR protein)">Fluorescent dyes or proteins</option><option value=""Luminescent agents"">Luminescent agents</option><option value="(Metals OR Metal OR Gold OR Au)">Metals (Au)</option><option value="Nanotubes">Nanotubes</option><option value=""Quantum dots"">Quantum dots</option></optgroup><optgroup label="PET radionuclides"><option value="("Arsenic 74" OR 74As)">Arsenic-74</option><option value="("Bromine 76" OR 76Br)">Bromine-76</option><option value="("Carbon 11" OR 11C)">Carbon-11</option><option value="(Copper-60 OR Copper-61 OR Copper-62 OR Copper-64 OR 60Cu OR 61Cu OR 62Cu OR 64Cu)">Copper-60, 61, 62, 64</option><option value="("Fluorine 18" OR 18F)">Fluorine-18</option><option value="(Gallium-68 OR 68Ga)">Gallium-68</option><option value="("Iodine 124" OR 124I)">Iodine-124</option><option value="("Nitrogen 13" OR 13N)">Nitrogen-13</option><option value="("Yttrium 86" OR 86Y)">Yttrium-86</option><option value="("Zirconium 89" OR 89Zr)">Zirconium-89</option></optgroup><optgroup label="Photoacoustic agents"><option value="(Gold OR Au)">Gold</option><option value="("Indocyanine green" OR ICG)">Indocyanine green</option></optgroup><optgroup label="SPECT radionuclides"><option value="(Gallium-67 OR 67Ga)">Gallium-67</option><option value="("Indium 111" OR 111In)">Indium-111</option><option value="("Iodine 123" OR "Iodine 125" OR "Iodine 131" OR 123I OR 125I OR 131I)">Iodine-123, 125, 131</option><option value="("Lutetium 177" OR 177Lu)">Lutetium-177</option><option value="(Rhenium OR 186Re OR 188Re)">Rhenium</option><option value="("Technetium 99m" OR 99mTc)">Technetium-99m</option><option value="("Tellurium 125m" OR 125mTe)">Tellurium-125m</option></optgroup><optgroup label="Ultrasound agents"><option value="Microbubbles">Microbubbles</option><option value="Nanobubbles">Nanobubbles</option></optgroup><optgroup label="X-ray and CT agents"><option value="(Bismuth OR Bi)">Bismuth</option><option value="(Gold OR Au)">Gold</option><option value="Iodine">Iodine</option></optgroup></select></div></div><div class="clearfix"><label for="agent">Agent Category:</label><div class="right"><select name="agent" id="agent" style="width:200px"><option value="" selected="selected">Any</option><option value="(antibody OR trastuzumab OR immunoglobulin)">Antibodies</option><option value="(bacteria OR bacteriophage OR coli)">Bacteria</option><option value="cell">Cells</option><option value="(compound OR "amino acid" OR "folic acid" OR "cage molecule" OR carbohydrate OR copolymers OR polymer OR "small molecule" OR macromolecule OR triiodobenzoate OR estradiol OR glycosaminoglycan)">Compounds</option><option value="ligand">Ligands</option><option value="(lipid OR liposome OR liposomes">Lipids</option><option value="metal">Metal</option><option 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 receptor-antibody OR antibody-receptor)">Receptors</option><option value="transporter">Transporters</option><option value="non-targeted">Non-targeted</option><option value=""nucleic acid"">Nucleic acids</option><option value="(non-targeted OR "unknown binding site")">Others</option></select></div></div><div><input id="__micad_btn_1" type="radio" name="stage" value="vitro" /><label for="__micad_btn_1"><i>In vitro</i></label><input id="__micad_btn_2" type="radio" name="stage" value="rodents" /><label for="__micad_btn_2">Rodents</label><input id="__micad_btn_3" type="radio" name="stage" value="mammals" /><label for="__micad_btn_3">Non-primate non-rodent mammals</label><br /><input id="__micad_btn_4" type="radio" name="stage" value="primates" /><label for="__micad_btn_4">Non-human primates</label><input id="__micad_btn_5" type="radio" name="stage" value="humans" /><label for="__micad_btn_5">Humans</label><input id="__micad_btn_6" type="radio" name="stage" value="any" checked="checked" /><label for="__micad_btn_6">Any</label></div></form><form xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" name="frmGo" method="get" action="javascript:alert('frmGo:_@action_was_not_set')" id="frmGo"><input name="term" value="." type="hidden" /></form></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=1512912" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=1512912" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20641798" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (111)In-DOTA-Re(Cys(3,4,10),d-Phe(7),Arg(11))αMSH(3-13).</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop 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ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> [NIe(4),Asp(5),d-Phe(7), (67)Ga/(68)Ga-1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-1,4,7,10-tetraacetic acid-Lys(11)]-α-MSH(4-11).</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> [NIe(4),Asp(5),d-Phe(7), (67)Ga/(68)Ga-1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-1,4,7,10-tetraacetic acid-Lys(11)]-α-MSH(4-11).<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Cheng KT. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=20641499" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=20641499" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a 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