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<title>Fibroblast activation protein α–specific, near-infrared peptide probe (KGPGPNQC) linked to Cy5.5 and a quencher dye, QSY21 - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf</title>
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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="Molecular Imaging and Contrast Agent Database (MICAD) [Internet]" /><meta name="citation_title" content="Fibroblast activation protein α–specific, near-infrared peptide probe (KGPGPNQC) linked to Cy5.5 and a quencher dye, QSY21" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2012/11/21" /><meta name="citation_author" content="Arvind Chopra" /><meta name="citation_pmid" content="23193619" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK114336/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Fibroblast activation protein α–specific, near-infrared peptide probe (KGPGPNQC) linked to Cy5.5 and a quencher dye, QSY21" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Center for Biotechnology Information (US)" /><meta name="DC.Contributor" content="Arvind Chopra" /><meta name="DC.Date" content="2012/11/21" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK114336/" /><meta name="description" content="The fibroblast activation protein α (FAPα; also known as seprase) is a tumor stromal fibroblast cell-surface dipeptidyl peptidase IV (DPPIV) serine protease that is expressed in various pathologies such as cancers (colon-rectal, pancreas, lung, ovarian, etc.), arthritis, fibrosis, and inflammation, but not in normal tissues (1). 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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="#__NBK114336_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK114336_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/LXY2-Cy55/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/cMBPAOCCy55/" 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="_NBK114336_"><span class="title" itemprop="name">Fibroblast activation protein α–specific, near-infrared peptide probe (KGPGPNQC) linked to Cy5.5 and a quencher dye, QSY21</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">ANP<sub>FAP</sub></div><p class="contrib-group"><span itemprop="author">Arvind Chopra</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK114336_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK114336_ai__"><div class="contrib half_rhythm"><span itemprop="author">Arvind Chopra</span>, PhD<div class="affiliation small">National Center for Biotechnology Information, NLM, Bethesda, MD 20894<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><p class="small">Created: <span itemprop="datePublished">October 31, 2012</span>; Last Update: <span itemprop="dateModified">November 21, 2012</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="Cy55AFPQSY21.T.nc_chemical_namefibroblas" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK114336/table/Cy55AFPQSY21.T.nc_chemical_namefibroblas/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Cy55AFPQSY21.T.nc_chemical_namefibroblas_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;">Fibroblast activation protein α–specific, near-infrared peptide probe (KGPGPNQC) linked to Cy5.5 and a quencher dye, QSY21</td><td rowspan="9" colspan="1" style="text-align:center;vertical-align:middle;">
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<span class="graphic"><img src="/books/NBK114336/bin/Cy55ANPQSY21.jpg" alt="Image Cy55ANPQSY21.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;">ANP<sub>FAP</sub><br /></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;"></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;">Fibroblast activation protein-α</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;">Enzyme</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;">Near-infrared (NIFR) imaging; optical imaging</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Source of signal / contrast:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cy5.5</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;">Yes</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;">Structure of ANP<sub>FAP</sub></td></tr></tbody></table></div></div><div id="Cy55AFPQSY21.Background"><h2 id="_Cy55AFPQSY21_Background_">Background</h2><p>[<a href="/pubmed?term=fibroblast%20activation%20protein%20review&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The fibroblast activation protein α (FAPα; also known as seprase) is a tumor stromal fibroblast cell-surface dipeptidyl peptidase IV (DPPIV) serine protease that is expressed in various pathologies such as cancers (colon-rectal, pancreas, lung, ovarian, etc.), arthritis, fibrosis, and inflammation, but not in normal tissues (<a class="bk_pop" href="#Cy55AFPQSY21.REF.1">1</a>). Although the exact function of FAPα in the development of the different diseases is not clear, it is believed to participate in the progression and metastasis of cancer, angiogenesis, and the suppression of the antitumor response of the immune system (<a class="bk_pop" href="#Cy55AFPQSY21.REF.1">1</a>). Because of its role in the ontogeny of various pathological conditions, FAPα is considered an excellent target for the detection and treatment of different diseases, particularly cancer (<a class="bk_pop" href="#Cy55AFPQSY21.REF.2">2</a>). A small molecule inhibitor of FAPα has been evaluated in a phase II clinical trial for the treatment of metastatic colorectal cancer (<a class="bk_pop" href="#Cy55AFPQSY21.REF.3">3</a>). Therefore, probes that can be used with noninvasive imaging can be of much value for the early detection of cancer, to screen for patients who would benefit most from an anti-FAPα therapy, and to monitor patients for treatment response (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>).</p><p>Targeted, activatable, near-infrared (NIR) fluorescent probes (ANP<sub>FAP</sub>) based on fluorescence resonance energy transfer (FRET), that target proteases such as matrix metalloproteinases (MMP) (<a class="bk_pop" href="#Cy55AFPQSY21.REF.5">5</a>), cysteine proteases (<a class="bk_pop" href="#Cy55AFPQSY21.REF.6">6</a>), and caspase (<a class="bk_pop" href="#Cy55AFPQSY21.REF.7">7</a>) have been successfully used to detect cancerous tumors. However, no such probe that targets the FAPα is available (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>). Li et al. developed a FRET probe that was selectively activated by FAPα, and showed that it was suitable for the <i>in vivo</i> detection of tumors that express activation protein in mice (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>). The probe consists of the NIR dye Cy5.5, which is linked to QSY21, a quencher dye, through a peptide (ANP; sequence KGPGPNQC) that specifically binds to and is a substrate for the FAPα.</p><div id="Cy55AFPQSY21.Related_Resource_Links"><h3>Related Resource Links</h3><p>Related chapters in <a href="/books/?term=FRET+AND+micad%5Bbook%5D&view=chapter&p%24a=&p%24l=PBooksLayout&p%24st=books" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MICAD</a></p><p><a href="http://clinicaltrials.gov/ct2/results?term=fibroblast+activation+protein&Search=Search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Clinical trials</a> related to FAPα</p><p>FAPα in <a href="/gene/2191" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Gene database</a> (Gene ID: 2191)</p><p><a href="http://omim.org/entry/600403" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FAPα</a> in Online Mendalian Inheritance in man database (OMIM)</p><p><a href="/nuccore/NM_004460.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Protein and mRNA</a> sequences of human FAPα (seprase)</p></div></div><div id="Cy55AFPQSY21.Synthesis"><h2 id="_Cy55AFPQSY21_Synthesis_">Synthesis</h2><p>[<a href="/pubmed?term=Fibroblast%20activation%20protein%20probe%20synthesis&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The synthesis of ANP<sub>FAP</sub> peptide has been described by Li et al. (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>). The substrate peptide was synthesized on an automatic peptide synthesizer. The final product was purified with reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The purified peptide was then conjugated with Cy5.5, and the NIR dye-labeled ANP was purified with RP-HPLC. The Cy5.5-peptide was characterized with MALDI-TOF-MS before use for the next step. The Cy5.5-peptide was then conjugated with QSY21 to obtain ANP<sub>FAP</sub>, the activatable NIR probe. The final preparation of ANP<sub>FAP</sub> was purified with RP-HPLC and characterized with MALDI-TOF-MS. The final yield of ANP<sub>FAP</sub> was reported to be ~26% and had a purity of >95%.</p><p>A fluorescence spectrum analysis of Cy5.5-labeled ANP and ANP<sub>FAP</sub> showed that the quenching efficiency of QSY21 in the probe was 94% (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>).</p></div><div id="Cy55AFPQSY21.In_Vitro_Studies_Testing_in"><h2 id="_Cy55AFPQSY21_In_Vitro_Studies_Testing_in_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/pubmed?term=Fibroblast%20activation%20protein%20probe%20In%20Vitro%20Studies&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The specificity of ANP<sub>FAP</sub> for FAPα was established by incubating 10 μM of the probe with 1 μg/mL FAPα, 1 μg/mL DPPIV, and 1 μg/mL MMP, respectively, for 1 h at 37°C (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>). At the end of incubation, only the ANP<sub>FAP</sub>/FAPα reaction showed a 12-fold increase in fluorescence emission intensity compared with controls (ANP<sub>FAP</sub> incubated without FAPα under the same <i>in vitro</i> conditions as the test samples), and the fluorescence emission spectrum of the ANP<sub>FAP</sub>/FAPα reaction corresponded to that of Cy5.5. No increase in fluorescence emission was observed with either DPPIV or MMP. This indicated that the ANP<sub>FAP</sub> probe was cleaved only by FAPα, and the release of QSY21 from the FRET pair resulted in the generation of fluorescence by Cy5.5. Incubation of ANP<sub>FAP</sub> with increasing concentrations of FAPα (ranging from 0.25 μg/mL to 1.0 μg/mL) for 1 h at 37°C showed that the increase of fluorescence in the reaction mixture corresponded well with the amount of FAPα present in the reaction mixture (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>).</p><p>The expression of FAPα in <a href="https://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=HTB-14&Template=cellBiology" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">U87MG cells</a> (human glioblastoma cells that express FAPα) and <a href="https://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=CCL-107&Template=cellBiology" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">C6 cells</a> (rat fibroblasts that do not express FAPα), which were used to generate tumors in mice, was confirmed with Western blot analysis (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>). An anti-FAP monoclonal antibody (Ab) was used as the primary Ab for the blots, and the protein bands were visualized with an anti-rabbit horseradish peroxidase–conjugated secondary Ab. From the blots it was evident that only the U87MG cells expressed high levels of FAPα.</p></div><div id="Cy55AFPQSY21.Animal_Studies"><h2 id="_Cy55AFPQSY21_Animal_Studies_">Animal Studies</h2><div id="Cy55AFPQSY21.Rodents"><h3>Rodents</h3><p>[<a href="/pubmed?term=Fibroblast%20activation%20protein%20probe%20rodentia&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Mice bearing C6 cell tumors (controls) or U87MG cell tumors (<i>n</i> = 5 animals/group) were injected with 1 nmol ANP<sub>FAP</sub> through the tail vein, and whole-body fluorescence images of the rodents were acquired at time points ranging from 0.5 h to 4 h postinjection (p.i.), with the use of a Cy5.5 filter (background 580–610 nm; excitation 615–665 nm and emission 695–770 nm) as described by Li et al. (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>). For comparison, all of the fluorescence emission data were normalized to photons per second per centimeter squared per <a href="http://www.princeton.edu/~achaney/tmve/wiki100k/docs/Steradian.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">steradian</a> (p/s/cm<sup>2</sup>/sr). In contrast to the C6 cell tumors, strong fluorescent signals were obtained from the U87MG cell tumors (<i>P</i> < 0.05) at 0.5 h p.i. The intensity of the fluorescence signals from the U87MG lesions peaked at 2 h p.i. and remained constant thereafter. No such increase in fluorescence signal intensity was observed with the C6 cell tumors. The tumor/normal tissue fluorescence ratios (T/N ratio) of the U87MG lesions increased from 2.22 ± 0.40 at 0.5 h p.i. to 4.63 ± 0.73 at 4 h p.i., indicating there was an accumulation of the Cy5.5 probe in the tumors. The T/N ratio of the C6 cell tumors remained constant during the same time period. Although no blocking studies were reported, the investigators concluded that ANP<sub>FAP</sub> exhibited a high <i>in vivo</i> specificity to target FAPα expressed on the U87MG cell lesions in rodents.</p><p>At the end of the imaging session at 4 h p.i., the rodents were euthanized, and all organs of interest, including the tumors, were retrieved from the animals for <i>ex vivo</i> imaging (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>). The U87MG cell tumors had a significantly higher fluorescence signal (<i>P</i> < 0.05) compared with the C6 cell lesions as observed earlier during the <i>in vivo</i> studies. The high fluorescence signal generated in the stomachs of mice in both groups was attributed to the autofluorescence of mouse chow present in these organs. All other organs from the two groups of animals produced comparable low fluorescence signals. The T/N ratio of the U87MG cell tumors was significantly higher (<i>P</i> < 0.05) than that of the C6 cell tumors (~30 <i>versus</i> ~9).</p><p>From these studies, the investigators concluded that ANP<sub>FAP</sub> was a suitable probe to detect tumors that express FAPα in rodents (<a class="bk_pop" href="#Cy55AFPQSY21.REF.4">4</a>).</p></div><div id="Cy55AFPQSY21.Other_NonPrimate_Mammals"><h3>Other Non-Primate Mammals</h3><p>[<a href="/pubmed?term=Fibroblast%20activation%20protein%20probe%20Other%20Non-Primate%20Mammals&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="Cy55AFPQSY21.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/pubmed?term=Fibroblast%20activation%20protein%20probe%20Non-Human%20Primates&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="Cy55AFPQSY21.Human_Studies"><h2 id="_Cy55AFPQSY21_Human_Studies_">Human Studies</h2><p>[<a href="/pubmed?term=Fibroblast%20activation%20protein%20probe%20Human%20Studies&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="Cy55AFPQSY21.Supplemental_Information"><h2 id="_Cy55AFPQSY21_Supplemental_Information_">Supplemental Information</h2><p>[<a href="/books/n/micad/disclaimer/">Disclaimers</a>]</p><p>No information is currently available.</p></div><div id="Cy55AFPQSY21.NIH_Support"><h2 id="_Cy55AFPQSY21_NIH_Support_">NIH Support</h2><p>Supported in part by grant 5R01 CA119053 from the National Cancer Institute of the National Institutes of Health.</p></div><div id="Cy55AFPQSY21.References"><h2 id="_Cy55AFPQSY21_References_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="Cy55AFPQSY21.REF.1">Kelly T., Huang Y., Simms A.E., Mazur A.
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<em>Fibroblast activation protein-alpha: a key modulator of the microenvironment in multiple pathologies.</em>
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<span><span class="ref-journal">Int Rev Cell Mol Biol. </span>2012;<span class="ref-vol">297</span>:83–116.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22608558" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22608558</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="Cy55AFPQSY21.REF.2">Lo P.C., Chen J., Stefflova K., Warren M.S., Navab R., Bandarchi B., Mullins S., Tsao M., Cheng J.D., Zheng G.
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<em>Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers.</em>
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||
<span><span class="ref-journal">J Med Chem. </span>2009;<span class="ref-vol">52</span>(2):358–68.</span> [<a href="/pmc/articles/PMC2773291/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2773291</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19093877" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19093877</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="Cy55AFPQSY21.REF.3">Narra K., Mullins S.R., Lee H.O., Strzemkowski-Brun B., Magalong K., Christiansen V.J., McKee P.A., Egleston B., Cohen S.J., Weiner L.M., Meropol N.J., Cheng J.D.
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<em>Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer.</em>
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||
<span><span class="ref-journal">Cancer Biol Ther. </span>2007;<span class="ref-vol">6</span>(11):1691–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18032930" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18032930</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="Cy55AFPQSY21.REF.4">Li J., Chen K., Liu H., Cheng K., Yang M., Zhang J., Cheng J.D., Zhang Y., Cheng Z.
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<em>Activatable near-infrared fluorescent probe for in vivo imaging of fibroblast activation protein-alpha.</em>
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<span><span class="ref-journal">Bioconjug Chem. </span>2012;<span class="ref-vol">23</span>(8):1704–11.</span> [<a href="/pmc/articles/PMC3419799/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3419799</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22812530" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22812530</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="Cy55AFPQSY21.REF.5">Roy R., Zurakowski D., Pories S., Moss M.L., Moses M.A.
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<em>Potential of fluorescent metalloproteinase substrates for cancer detection.</em>
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<span><span class="ref-journal">Clin Biochem. </span>2011;<span class="ref-vol">44</span>(17-18):1434–9.</span> [<a href="/pmc/articles/PMC3232457/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3232457</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22001071" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22001071</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="Cy55AFPQSY21.REF.6">Abd-Elgaliel W.R., Cruz-Monserrate Z., Logsdon C.D., Tung C.H.
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<em>Molecular imaging of Cathepsin E-positive tumors in mice using a novel protease-activatable fluorescent probe.</em>
|
||
<span><span class="ref-journal">Mol Biosyst. </span>2011;<span class="ref-vol">7</span>(12):3207–13.</span> [<a href="/pmc/articles/PMC4207267/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4207267</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21935563" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21935563</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="Cy55AFPQSY21.REF.7">Barnett E.M., Zhang X., Maxwell D., Chang Q., Piwnica-Worms D.
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<em>Single-cell imaging of retinal ganglion cell apoptosis with a cell-penetrating, activatable peptide probe in an in vivo glaucoma model.</em>
|
||
<span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2009;<span class="ref-vol">106</span>(23):9391–6.</span> [<a href="/pmc/articles/PMC2695102/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2695102</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19458250" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19458250</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: NBK114336</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/23193619" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">23193619</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/LXY2-Cy55/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/cMBPAOCCy55/" title="Next page in this title">Next ></a></div></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/NBK114336/?report=reader">PubReader</a></li><li><a href="/books/NBK114336/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK114336" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK114336" style="display:none" title="Cite this Page"><div class="bk_tt">Chopra A. Fibroblast activation protein α–specific, near-infrared peptide probe (KGPGPNQC) linked to Cy5.5 and a quencher dye, QSY21. 2012 Oct 31 [Updated 2012 Nov 21]. 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/NBK114336/pdf/Bookshelf_NBK114336.pdf">PDF version of this page</a> (385K)</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="#Cy55AFPQSY21.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#Cy55AFPQSY21.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#Cy55AFPQSY21.In_Vitro_Studies_Testing_in" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#Cy55AFPQSY21.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#Cy55AFPQSY21.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#Cy55AFPQSY21.Supplemental_Information" ref="log$=inpage&link_id=inpage">Supplemental Information</a></li><li><a href="#Cy55AFPQSY21.NIH_Support" ref="log$=inpage&link_id=inpage">NIH Support</a></li><li><a href="#Cy55AFPQSY21.References" ref="log$=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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