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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>99mTc-Labeled acetylated dendrimer poly(amido)-amine generation 5-folic acid-2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid conjugate - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf</title>
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<meta name="citation_title" content="99mTc-Labeled acetylated dendrimer poly(amido)-amine generation 5-folic acid-2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid conjugate">
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<meta name="citation_date" content="2011/04/21">
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<meta name="citation_author" content="Liang Shan">
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<meta name="og:description" content="99mTc-Labeled acetylated (Ac) dendrimer poly(amido)-amine (PAMAM) generation 5 (G5)-folic acid (FA)-2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid (1B4M DTPA) conjugate, abbreviated as 99mTc-G5-Ac-FA-DTPA, was synthesized by Zhang et al. for folate receptor (FR)-targeted imaging of FR-positive tumors (1, 2).">
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stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK54068_"><span class="title" itemprop="name"><sup>99m</sup>Tc-Labeled acetylated dendrimer poly(amido)-amine generation 5-folic acid-2-(<i>p</i>-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid conjugate</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"><sup>99m</sup>Tc-G5-Ac-FA-DTPA</div><p class="contribs">Shan L.</p><p class="fm-aai"><a href="#_NBK54068_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figTcAcFATncchemicalname99mtclabeled"><a href="/books/NBK54068/table/Tc-Ac-FA.T.nc_chemical_name99mtclabeled_/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobTcAcFATncchemicalname99mtclabeled"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="Tc-Ac-FA.T.nc_chemical_name99mtclabeled_"><a href="/books/NBK54068/table/Tc-Ac-FA.T.nc_chemical_name99mtclabeled_/?report=objectonly" target="object" rid-ob="figobTcAcFATncchemicalname99mtclabeled">Table</a></h4><p class="float-caption no_bottom_margin">
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<i>In vitro</i>
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Rodents
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</p></div></div><div id="Tc-Ac-FA.Background"><h2 id="_Tc-Ac-FA_Background_">Background</h2><p>[<a href="/pubmed/?term=folate+and+dendrimer+and+imaging" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p><sup>99m</sup>Tc-Labeled acetylated (Ac) dendrimer poly(amido)-amine (PAMAM) generation 5 (G5)-folic acid (FA)-2-(<i>p</i>-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid (1B4M DTPA) conjugate, abbreviated as <sup>99m</sup>Tc-G5-Ac-FA-DTPA, was synthesized by Zhang et al. for folate receptor (FR)-targeted imaging of FR-positive tumors (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2">1, 2</a>).</p><p>Folate is an essential vitamin for cell synthesis of nucleotide bases. Some unique features of the FR-folate system make it extremely valuable for developing FR-targeted imaging and therapeutic agents (<a class="bibr" href="#Tc-Ac-FA.REF.3" rid="Tc-Ac-FA.REF.3 Tc-Ac-FA.REF.4 Tc-Ac-FA.REF.5">3-5</a>). First, FR has a high affinity for the exogenous folate conjugates (<i>K</i><sub>d</sub> = ~100 pM), but they are inaccessible for the conjugates in most normal tissues. Second, FR-α isoform is overexpressed on ~40% of human cancers, where it is completely accessible to folate conjugates. Third, folate conjugates are taken up by cancer cells <i>via</i> FR-mediated endocytosis, and FR recycles actively to the cell surface with a frequency of 5.7–20 h depending on cell types. Fourth, conjugation of imaging labels <i>via</i> the γ-carboxyl group of folate has no apparent effects on the ligand-binding affinity to FR. Furthermore, folate is a small molecule (MW = ~441) that exhibits rapid and complete penetration of solid tumors and rapid clearance from FR-negative tissues (<i>t</i><sub>1/2</sub>, <10 min). One disadvantage of the FR-folate system is that FR expresses at a relatively low density on some tumor cell surface (1–3 million FR/cell), which means that the FR-folate binding can be saturated rapidly and the imaging contrast will be limited (<a class="bibr" href="#Tc-Ac-FA.REF.3" rid="Tc-Ac-FA.REF.3 Tc-Ac-FA.REF.4 Tc-Ac-FA.REF.6">3, 4, 6</a>). Sensitive imaging techniques such as positron emission tomography and single-photon emission computed tomography (SPECT) are more desirable for FR-targeted imaging (<a class="bibr" href="#Tc-Ac-FA.REF.3" rid="Tc-Ac-FA.REF.3 Tc-Ac-FA.REF.4 Tc-Ac-FA.REF.7">3, 4, 7</a>). To date, a large set of folate-based radiopharmaceutical agents have been synthesized for nuclear imaging (<a class="bibr" href="#Tc-Ac-FA.REF.8" rid="Tc-Ac-FA.REF.8">8</a>). In general, a chelating agent is necessary to bridge the radiolabels and the folate molecule. The chelating agent is also critical for optimizing the molecular properties of conjugates (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2 Tc-Ac-FA.REF.9">1, 2, 9</a>).</p><p>Dendrimers represent a unique class of nanostructures that are synthesized from branched monomers in a step-wise manner. The molecular properties of dendrimers can be precisely controlled by choosing different branching monomers and surface functional groups (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2 Tc-Ac-FA.REF.9">1, 2, 9</a>). PAMAM is one of the most extensively studied dendrimers. Zhang et al. synthesized two folate-based compounds, <sup>99m</sup>Tc-G5-Ac-pegFA-DTPA and <sup>99m</sup>Tc-G5-Ac-FA-DTPA, and one control, <sup>99m</sup>Tc-G5-Ac-DTPA, with PAMAM G5 dendrimer and folate (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2">1, 2</a>). To increase the solubility and decrease the nonspecific cellular uptake of the agents, the primary amines on the surface of PAMAM dendrimers were partially converted to acetamide moieties, which were used to link with the bifunctional chelating agent 1B4M DTPA. Folate was either PEGylated or left unPEGylated, and its c-carboxyl group was used to conjugate with the primary amine of PAMAM. The two folate-based conjugates exhibited excellent stability, rapid clearance from blood, and high accumulation in tumor xenografts (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2">1, 2</a>). This chapter describes the results obtained with <sup>99m</sup>Tc-G5-Ac-FA-DTPA. Another chapter in MICAD describes the data obtained with <a href="/books/NBK5330/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri"><sup>99m</sup>Tc-G5-Ac-pegFA-DTPA</a>.</p><div id="Tc-Ac-FA.Related_Resource_Links"><h3>Related Resource Links:</h3><ul><li class="half_rhythm"><div><a href="/books/?term=folate%20receptor%20AND%20micad%5bbook%5d" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FR-targeted chapters</a> on MICAD</div></li><li class="half_rhythm"><div><a href="/protein/?term=Folate+Receptor" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Protein</a> and <a href="/nucleotide/?term=Folate+Receptor" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">nucleotide</a> information of FR</div></li><li class="half_rhythm"><div><a href="http://clinicaltrials.gov/ct2/results?term=Folate+Receptor" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FR-targeted clinical trials</a> in Clinicaltrials.gov</div></li></ul></div></div><div id="Tc-Ac-FA.Synthesis"><h2 id="_Tc-Ac-FA_Synthesis_">Synthesis</h2><p>[<a href="/pubmed/20350006" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Zhang et al. described the synthesis of <sup>99m</sup>Tc-G5-Ac-pegFA-DTPA, <sup>99m</sup>Tc-G5-Ac-FA-DTPA, and <sup>99m</sup>Tc-G5-Ac-DTPA (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2">1, 2</a>). The primary amines on the surface of G5 PAMAM dendrimers were first partially converted to acetamide moieties (G5-Ac, yield = 94.7%). PEGylated folate (NHS-PEG1540-FA) was synthesized through reactions of <i>N</i>-hydroxysuccinimide ester of FA with poly(ethylene glycol)bis amine (NH<sub>2</sub>-PEG1540-NH<sub>2</sub>). Conjugation of the folate or PEGylated folate to the dendrimers was achieved <i>via</i> condensation between the γ-carboxyl group of folate and the primary amine of dendrimer (G5-Ac-FA or G5-Ac-pegFA, yield = 90.8%). The partially acetylated dendrimers were then linked with the chelating agent 1B4M DTPA to generate G5-Ac-FA-DTPA, G5-Ac-pegFA-DTPA, or G5-Ac-DTPA (yield = 98.2%). Each G5-Ac-DTPA contained 77 acetyl and 8 DTPA molecules. Each G5-Ac-FA-DTPA contained 77 acetyl, 4.8 folic acid molecules, and 7 DTPA molecules, and each G5-Ac-pegFA-DTPA contained 77 acetyl, 5.2 folic acid molecules, and 8 DTPA molecules. Therefore, the three compounds (G5-Ac-pegFA-DTPA, G5-Ac-FA-DTPA, and G5-Ac-DTPA) contained a similar number of DTPA molecules (i.e., 7 or 8 molecules). The two folate conjugates (G5-Ac-pegFA-DTPA and G5-Ac-FA-DTPA) contained a similar number of folic acid molecules (i.e., 4.8 to 5.2 molecules).</p><p>Radiolabeling was performed after reduction of <sup>99m</sup>TcO4− to reduced <sup>99m</sup>Tc using stannous chloride. The radiochemical yield and radioactivity of the three radiolabeled agents were >95% and 88.3 ± 1.0%, respectively. They were used for experiments without further purification. The partition ratios (log <i>P</i>) between n-octanol and water were −2.030, −2.061, and −2.167 for <sup>99m</sup>Tc-G5-Ac-FA-DTPA, <sup>99m</sup>Tc-G5-Ac-pegFA-DTPA, and <sup>99m</sup>Tc-G5-Ac-DTPA, respectively, indicating that the agents had high water solubility.</p></div><div id="Tc-Ac-FA.In_Vitro_Studies_Testing_in_Cel"><h2 id="_Tc-Ac-FA_In_Vitro_Studies_Testing_in_Cel_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/pubmed/20350006" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The <i>in vitro</i> stability was analyzed after incubation of the <sup>99m</sup>Tc-G5-Ac-FA-DTPA, <sup>99m</sup>Tc-G5-Ac-pegFA-DTPA, and <sup>99m</sup>Tc-G5-Ac-DTPA with phosphate-buffered saline and new-born calf serum, respectively. After incubation for 6 h at 37ºC, at least 86% and 84% of the agents kept their original structure in phosphate-buffered saline and in new-born calf serum, respectively, indicating high stability.</p><p>Cell uptake of the three agents was quantitatively measured with FR-expressing KB cells (a human oral epidermoid carcinoma line) (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2">1, 2</a>). <i>In vitro</i> cell binding of the <sup>99m</sup>Tc-G5-Ac-pegFA-DTPA was ~15% of total added radioactivity after incubation for 6 h at 37ºC, whereas <sup>99m</sup>Tc-G5-Ac-FA-DTPA and the control <sup>99m</sup>Tc-G5-Ac-DTPA exhibited lower binding ability (~11% and ~10%, respectively).</p><p>These results indicated that conjugation of FA directly to PAMAM dendrimers did not improve the cell uptake. In contrast, conjugation through a PEG spacer could improve the cellular internalization. Uptake of the three agents in the KB cells grown in FA-rich medium (to inhibit FR expression) was similar (<10%), suggesting no significant binding.</p></div><div id="Tc-Ac-FA.Animal_Studies"><h2 id="_Tc-Ac-FA_Animal_Studies_">Animal Studies</h2><div id="Tc-Ac-FA.Rodents"><h3>Rodents</h3><p>[<a href="/pubmed/20350006" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The <i>in vivo</i> studies on stability after injection into mice (<i>n</i> = 3/time point) showed that 80.45% of the <sup>99m</sup>Tc-G5-Ac-FA-DTPA, and 80.56% of the <sup>99m</sup>Tc-G5-Ac-DTPA remained intact within 6 h in blood of normal mice (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2">1, 2</a>).</p><p>The pharmacokinetics of the agents was studied in normal mice (<i>n</i> = 5). A rapid decrease was observed at 30 min after injection, followed by a slow clearance. The plasma half-life was estimated to be 13.75 min for the <sup>99m</sup>Tc-G5-Ac-FA-DTPA and 12.73 min for the control <sup>99m</sup>Tc-G5-Ac-DTPA. Less than 10% of the injected agents remained in circulation after 6 h (assuming that blood represents 5.5% of the total body mass).</p><p>Biodistribution was investigated with KB tumor–bearing nude mice (<i>n</i> = 3/time point). The mice were maintained on a folate-deficient diet for the duration of experiment to minimize the circulating levels of FA. Both <sup>99m</sup>Tc-G5-Ac-DTPA and <sup>99m</sup>Tc-G5-Ac-FA-DTPA were cleared rapidly from the blood, decreasing from 11.75% injected dose/gram (ID/g) at 2 h to 5.60% ID/g at 6 h for <sup>99m</sup>Tc-G5-Ac-DTPA and from 12.59% ID/g at 2 h to 4.00% ID/g at 6 h for <sup>99m</sup>Tc-G5-Ac-FA-DTPA. Both agents remained at a low level up to 6 h in the FR-negative organs, including brain.</p><p>The kidneys, which express FR, are the major clearance organs. The level of nontargeted <sup>99m</sup>Tc-G5-Ac-DTPA decreased from 32.08% ID/g at 2 h to 26.06% ID/g at 6 h. In contrast, the level of <sup>99m</sup>Tc-G5-Ac-FA-DTPA increased slightly with time (22.06% ID/g at 2 h to 28.18% ID/g at 6 h). In the liver, the concentrations of nontargeted <sup>99m</sup>Tc-G5-Ac-DTPA decreased with clearance from blood (41.07% ID/g at 2 h to 32.94% ID/g at 6 h), whereas the targeted <sup>99m</sup>Tc-G5-Ac-FA-DTPA decreased more slowly (32.02% ID/g at 2 h to 26.17% ID/g at 6 h). In the tumors, the level of <sup>99m</sup>Tc-G5-Ac-FA-DTPA increased from 3.10% ID/g at 2 h to 6.78% ID/g at 6 h. The nontargeted <sup>99m</sup>Tc-G5-Ac-DTPA also increased slightly from 2.81% ID/g at 2 h to 4.38% ID/g at 6 h.</p><p>Micro-SPECT imaging confirmed the predominant uptake of <sup>99m</sup>Tc-G5-Ac-FA-DTPA in the FR-positive tumors, liver, and kidneys in the KB tumor–bearing mice (<i>n</i> = 2/time point) (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2">1, 2</a>). Comparison among <sup>99m</sup>Tc-G5-Ac-pegFA-DTPA, <sup>99m</sup>Tc-G5-Ac-FA-DTPA, and <sup>99m</sup>Tc-G5-Ac-DTPA showed that PEGylation of the PAMAM dendrimer-FA conjugate improves the tumor targeting and may be used as a targeted delivery system for imaging labels and therapeutic drugs (<a class="bibr" href="#Tc-Ac-FA.REF.1" rid="Tc-Ac-FA.REF.1 Tc-Ac-FA.REF.2">1, 2</a>).</p></div><div id="Tc-Ac-FA.Other_NonPrimate_Mammals"><h3>Other Non-Primate Mammals</h3><p>[<a href="/pubmed/?term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20%28dog%20OR%20rabbit%20OR%20pig%20OR%20sheep%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="Tc-Ac-FA.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/pubmed/?term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20%28primate%20NOT%20human%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div></div><div id="Tc-Ac-FA.Human_Studies"><h2 id="_Tc-Ac-FA_Human_Studies_">Human Studies</h2><p>[<a href="/pubmed/?term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="Tc-Ac-FA.References"><h2 id="_Tc-Ac-FA_References_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.1">Zhang Y., Sun Y., Xu X., Zhu H., Huang L., Zhang X., Qi Y., Shen Y.M.
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<em>Radiosynthesis and micro-SPECT imaging of 99mTc-dendrimer poly(amido)-amine folic acid conjugate.</em>
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<span><span class="ref-journal">Bioorg Med Chem Lett. </span>2010;<span class="ref-vol">20</span>(3):927–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20045643" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20045643</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.2">Zhang Y., Sun Y., Xu X., Zhang X., Zhu H., Huang L., Qi Y., Shen Y.M.
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<em>Synthesis, biodistribution, and microsingle photon emission computed tomography (SPECT) imaging study of technetium-99m labeled PEGylated dendrimer poly(amidoamine) (PAMAM)-folic acid conjugates.</em>
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<span><span class="ref-journal">J Med Chem. </span>2010;<span class="ref-vol">53</span>(8):3262–72.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20350006" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20350006</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.3">Sega E.I., Low P.S.
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<em>Tumor detection using folate receptor-targeted imaging agents.</em>
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<span><span class="ref-journal">Cancer Metastasis Rev. </span>2008;<span class="ref-vol">27</span>(4):655–64.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18523731" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18523731</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.4">Low P.S., Kularatne S.A.
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<em>Folate-targeted therapeutic and imaging agents for cancer.</em>
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<span><span class="ref-journal">Curr Opin Chem Biol. </span>2009;<span class="ref-vol">13</span>(3):256–62.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19419901" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19419901</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.5">Zhao X., Li H., Lee R.J.
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<em>Targeted drug delivery via folate receptors.</em>
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<span><span class="ref-journal">Expert Opin Drug Deliv. </span>2008;<span class="ref-vol">5</span>(3):309–19.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18318652" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18318652</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.6">Miotti S., Bagnoli M., Ottone F., Tomassetti A., Colnaghi M.I., Canevari S.
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<em>Simultaneous activity of two different mechanisms of folate transport in ovarian carcinoma cell lines.</em>
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<span><span class="ref-journal">J Cell Biochem. </span>1997;<span class="ref-vol">65</span>(4):479–91.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9178098" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9178098</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.7">Altiparmak B., Lambrecht F.Y., Bayrak E., Durkan K.
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<em>Design and synthesis of 99mTc-citro-folate for use as a tumor-targeted radiopharmaceutical.</em>
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<span><span class="ref-journal">Int J Pharm. </span>2010;<span class="ref-vol">400</span>(1-2):8–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20696224" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20696224</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.8">Low P.S., Henne W.A., Doorneweerd D.D.
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<em>Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases.</em>
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<span><span class="ref-journal">Acc Chem Res. </span>2008;<span class="ref-vol">41</span>(1):120–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17655275" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17655275</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="Tc-Ac-FA.REF.9">Konda S.D., Aref M., Wang S., Brechbiel M., Wiener E.C.
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<em>Specific targeting of folate-dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts.</em>
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<span><span class="ref-journal">MAGMA. </span>2001;<span class="ref-vol">12</span>(2-3):104–13.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11390265" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11390265</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK54068_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Liang Shan</span>, PhD<div class="affiliation small">National Center for Biotechnology Information, NLM, NIH<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><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">March 15, 2011</span>; Last Update: <span itemprop="dateModified">April 21, 2011</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Shan L. 99mTc-Labeled acetylated dendrimer poly(amido)-amine generation 5-folic acid-2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid conjugate. 2011 Mar 15 [Updated 2011 Apr 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></p></div><div class="small-screen-prev"><a href="/books/n/micad/HYNIC-HBP99mTc/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/micad/Tc-Ac-pegFA/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobTcAcFATncchemicalname99mtclabeled"><div id="Tc-Ac-FA.T.nc_chemical_name99mtclabeled_" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK54068/table/Tc-Ac-FA.T.nc_chemical_name99mtclabeled_/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Tc-Ac-FA.T.nc_chemical_name99mtclabeled__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-Labeled acetylated dendrimer poly(amido)-amine generation 5-folic acid-2-(<i>p</i>-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid conjugate</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;"><sup>99m</sup>Tc-G5-Ac-FA-DTPA</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-Ac-G5-FA-1B4M DTPA</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;">Compounds</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;">Folate receptor</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 / contrast:</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;">No structure is available.</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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