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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>HSV1-TK/GFP/Fluc - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf</title>
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<meta name="citation_author" content="Huiming Zhang">
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rid-figpopup="figTGLT1" rid-ob="figobTGLT1"><img class="small-thumb" src="/books/NBK23131/table/TGL.T1/?report=thumb" src-large="/books/NBK23131/table/TGL.T1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="TGL.T1"><a href="/books/NBK23131/table/TGL.T1/?report=objectonly" target="object" rid-ob="figobTGLT1">Table</a></h4><p class="float-caption no_bottom_margin">
<i>In vitro</i>
Rodents
</p></div></div><div id="TGL.Background"><h2 id="_TGL_Background_">Background</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=HSV1-tk%20+%20GFP%20+%20luciferase" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Reporter genes, also known as marker genes, possess a measurable phenotype distinguishable from the background of endogenous proteins (<a class="bibr" href="#TGL.REF.1" rid="TGL.REF.1">1</a>). Several reporter genes express proteins that can generate signals for <i>in vivo</i> imaging, such as the herpes simplex virus type 1 thymidine kinase (HSV1-TK) gene, the green fluorescence protein (GFP) gene, and the firefly luciferase (Fluc) gene (<a class="bibr" href="#TGL.REF.2" rid="TGL.REF.2">2</a>). The reporter gene is constructed with a &#x0201c;constitutive&#x0201d; promoter for continuous transcriptions or with an &#x0201c;inducible&#x0201d; promoter for controlled transcriptions (<a class="bibr" href="#TGL.REF.3" rid="TGL.REF.3">3</a>). Both types of gene constructs have been used in the expression of exogenous genes and/or endogenous genes to monitor the levels of gene delivery and the efficiency in cell/tissue transduction in gene therapy.</p><p>HSV1-TK/GFP/Fluc (TGL, Mw = 130 kDa) is a triple reporter protein used for multimodal <i>in vivo</i> imaging of gene expression (<a class="bibr" href="#TGL.REF.4" rid="TGL.REF.4">4</a>) with single photon emission computed tomography (SPECT) or fluorescence and bioluminescence imaging. TGL is produced from the expression of a triple-fusion reporter gene (TGL gene) in which transcription and translation are processed through a single open reading frame. TGL consists of three fused protein subunits: HSV1-TK, GFP, and Fluc, where polylysine is used as a linker to connect the protein subunits and to maintain the molecular stability in the fused protein. Each subunit corresponds to a specific imaging modality. HSV1-TK is a homodimer composed of two 376-residue subunits (<a class="bibr" href="#TGL.REF.5" rid="TGL.REF.5">5</a>), and it functions as a key enzyme in the pyrimidine-salvage pathway to catalyze the phosphorylation of thymidine (dT) to thymidine monophosphate (dTMP) in the presence of ATP and Mg<sup>2+</sup>. This feature has been used to design antiviral nucleoside analogs (i.e., ganciclovir) for antiviral therapy (<a class="bibr" href="#TGL.REF.5" rid="TGL.REF.5">5</a>) and radiolabeled substrates such as radiolabeled 2&#x02019;-fluoro-2&#x02019;-deoxy-1-&#x003b2;-D-arabino-furanosyl-5-iodo-uracil (FIAU) for SPECT imaging (<a class="bibr" href="#TGL.REF.6" rid="TGL.REF.6">6</a>). HSV can easily infect a variety of cells in that the expressed HSV1-TK can induce significant cytotoxicity in the presence of nucleoside analogs such as ganciclovir (<a class="bibr" href="#TGL.REF.7" rid="TGL.REF.7">7</a>). For this reason, HSV1-TK gene is also widely used as a suicide gene in cancer treatment. <sup>131</sup>I-Labeled FIAU is an active radiolabeled substrate of HSV1-TK that is detectable with SPECT (i.e., <sup>131</sup>I emits gamma-ray at 364 keV (81% abundance) with a half-life time of 8.02 days, which can be detected with a gamma camera or SPECT. GFP is a fluorescent protein of 238 amino acids that emits a bright green fluorescence (&#x003bb;<sub>max</sub> = 509 nm) when illuminated with a blue light (&#x003bb;<sub>max</sub> = 395 nm) (<a class="bibr" href="#TGL.REF.8" rid="TGL.REF.8">8</a>). The presence of the GFP subunit allows <i>in vitro</i>/<i>in vivo</i> fluorescence imaging and cell sorting with the fluorescence-activated cell sorting (FACS) technique. Fluc is an oxygenase (Mw = 62 kDa) extracted from <i>Photinus pyralis</i> (<a class="bibr" href="#TGL.REF.9" rid="TGL.REF.9">9</a>). In the presence of adenosine triphosphate (ATP) and O<sub>2</sub>, Fluc oxidizes the heterocyclic substrate <span class="small-caps">d</span>-luciferin to oxyluciferin and emits light in the wavelength range of 400&#x02013;620 nm (<a class="bibr" href="#TGL.REF.10" rid="TGL.REF.10">10</a>). The Fluc subunit allows for planar whole-body bioluminescence imaging of gene-transduced cells.</p></div><div id="TGL.Synthesis"><h2 id="_TGL_Synthesis_">Synthesis</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=(%20HSV1-tk%20+%20GFP%20+%20luciferase)+AND+synthesis%0D%0A" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Ponomarev et al. described the preparation of the HSV1-TK/GFP/Fluc expression vector in multiple steps (<a class="bibr" href="#TGL.REF.4" rid="TGL.REF.4">4</a>). First, a construct SFG-HSV1-TK/GFP was obtained (<a class="bibr" href="#TGL.REF.11" rid="TGL.REF.11">11</a>). Plasmid pLTKRNL was digested with restriction enzyme <i>Bam</i>HI to generate a 2.2-kb fragment that encoded the open reading frame of HSV1-TK. This fragment was ligated into plasmid pcDNA.1/Zeo to result in the 7.8-kb plasmid pTKZeo3.2; this ligation was followed by sequential digestions with <i>Bam</i>HI and <i>Xma</i>l to produce a 1.2-kb TK fragment. At the same time, plasmid pEGFP-N1 was digested sequentially with <i>BgI</i>II and <i>Xma</i>l to generate a 4.7-kb DNA fragment containing the open reading frame of GFP. The 1.2-kb fragment was then ligated with the 4.7-kb fragment to form the 5.9-kb expression plasmid pTKGFP, in which the TK-GFP cDNA was under control of the cytomegalovirus immediately early (IE) promoter. After the ligation, the plasmid was cloned into a retroviral vector, the Moloney murine leukemia virus-based SFG vector, to yield SFG-TK-GFP. Second, two modified constructs, SFG-NES-HSV1-TK/GFP and SFG-&#x00394;45-HSV1-TK/GFP, were obtained (<a class="bibr" href="#TGL.REF.6" rid="TGL.REF.6">6</a>). To generate SFG-NES-HSV1-TK/GFP, the Xenopus cDNA for encoding the 20 amino acids in the nuclear export signal (NES) sequence of the mitogen-activated protein (MAP) kinase kinase (MAPKK) was inserted into the N-terminus of HSV1-TK/GFP between His-9 and Ala-10 using <i>Mlu</i>L. To generate SFG-&#x00394;45-HSV1-TK/GFP, the &#x00394;45-HSV1 cDNA lacking the first 45 amino acids (135 nucleotides) of the original HSV1-TK was amplified with selective primers and subsequently cloned between the <i>Nco</i>l sites of SFG-HSV1-TK/GFP. Third, the commercially available cDNA of fused <i>Aequorea victoria</i> eGFP and Fluc (eGFP/Fluc) was obtained from the plasmid pEGF/Pluc and subcloned into the retroviral vector SFG-Ntp to yield the construct SFG-GL (<a class="bibr" href="#TGL.REF.4" rid="TGL.REF.4">4</a>). Finally, SFG-NES-HSV1-TK/GFP or SFG-&#x00394;45-HSV1-TK/GFP was treated with <i>Nco</i>l and the fragment containing NES-HSV1-TK or &#x00394;45-HSV1-TK was subcloned into the <i>Nco</i>I site of the SFG-GL to produce SFG-NES-HSV1-TK/GFP/Fluc (SFG-NES-TGL) or SFG-&#x00394;45-HSV1-TK/GFP/Fluc (SFG-&#x00394;45-TGL) (<a class="bibr" href="#TGL.REF.4" rid="TGL.REF.4">4</a>). [<sup>131</sup>I]-FIAU with &#x0003e;97% radiochemical purity was prepared by the iododestannylation reaction using the tin precursor and carrier-free <sup>131</sup>I.</p></div><div id="TGL.In_Vitro_Studies_Tes"><h2 id="_TGL_In_Vitro_Studies_Tes_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=(%20HSV1-tk%20+%20GFP%20+%20luciferase)+AND+%22in+vitro%22" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Ponomarev et al. assessed the integrity of the fused reporter proteins with Western blot analysis (<a class="bibr" href="#TGL.REF.4" rid="TGL.REF.4">4</a>). The molecular weight of the NES-TGL and &#x00394;45-TGL proteins as determined with Western blot analysis matched the predicted molecular weights. These proteins were further examined with anti-HSV1-TK, anti-GFP, and anti-Fluc antibodies to demonstrate the coexistence of the triple subunits in the full reporter proteins. Ponomarev et al. then imaged the cytoplasmic localizations of the NES-TGL and &#x00394;45-TGL reporter proteins with fluorescence microscopy (<a class="bibr" href="#TGL.REF.4" rid="TGL.REF.4">4</a>). Human glioma U87 cells were transduced with the retroviral vectors SFG-NES-TGL or SFG-&#x00394;45-TGL <i>in vitro</i>, followed by a bulk culture for 48 h. The obtained U87-NES-TGL cells or U87-&#x00394;45-TGL cells were sorted for positive GFP expression using FACS with 488-nm excitation beam and 510-nm emission filter. The subcellular localization of NES-TGL and &#x00394;45-TGL was visualized with fluorescence microscopy with similar excitation emission parameters. The GFP/Fluc signal appeared to be lower in the nucleus than in cytoplasm, but it was still detectable. Reporter gene expression in these transduced U87 cells was quantified with FACS, a bioluminescence assay, and a radiotracer [<sup>14</sup>C]-FIAU assay. The level of GFP fluorescence was found to be ~1.3 &#x000d7; 10<sup>3</sup> relative fluorescent units (RU) in the U87-NES-TGL cells and ~2.1 &#x000d7; 10<sup>3</sup> RU in the U87-&#x00394;45-TGL cells. The influx rate constant <i>Ki</i> of <sup>14</sup>C-labeled FIAU was ~1.4 media ml/min per g in the U87-NES-TGL cells and ~1.7 media ml/min per g in the U87-&#x00394;45-TGL cells. The bioluminescence was ~2.8 &#x000d7; 10<sup>3</sup> relative bioluminescence unit (RLU) in the U87-NES-TGL cells and ~4.9 &#x000d7; 10<sup>3</sup> RLU in the U87-&#x00394;45-TGL. The wild-type U87 cells were used as a control. Their measured fluorescence, influx rate, and bioluminescence were negligible.</p></div><div id="TGL.Animal_Studies"><h2 id="_TGL_Animal_Studies_">Animal Studies</h2><div id="TGL.Rodents"><h3>Rodents</h3><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=(%20HSV1-tk%20+%20GFP%20+%20luciferase)%20+AND++rodentia" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Ponomarev et al. used three imaging modalities to examine the expression of the triple reporter proteins <i>in vivo</i> (<a class="bibr" href="#TGL.REF.4" rid="TGL.REF.4">4</a>). <i>Nu</i>/<i>nu</i> mice (20&#x02013;25 g) were implanted subcutaneously with U87-NES-TGL cells on the right shoulder, with U87-&#x00394;45-TGL cells on the left shoulder, and with wild-type U87 cells on the left flank. The tumors grew to an average size of 5.4 &#x000b1; 2.1 mm and were imaged with whole-body fluorescence, bioluminescence, and gamma camera imaging. For bioluminescence imaging, mice were injected intravenously with 100 &#x003bc;l of D-luciferin solution at a dose of 150 mg/kg, and the images were acquired for 0.5&#x02013;10 s. For the gamma camera imaging, mice received an intraperitoneal injection of 0.9% NaI solution (1 ml) one day before imaging to block the thyroid uptake of radioactive iodide. Then the mice were injected intravenously with [<sup>131</sup>I]-FIAU at a dose of 7.4 MBq per animal. The gamma camera images were collected 24 h after [<sup>131</sup>I]-FIAU injection to allow sufficient clearance of body background radioactivity. The GFP fluorescence was collected with a charge-coupled device (CCD) camera. The average level of gene expression in the implanted U87-NES-TGL tumor was detected as 707 &#x000b1; 36 in fluorescence, 486 &#x000b1; 47 &#x000d7; 10<sup>6</sup> photons/cm<sup>2</sup> per sr in bioluminescence, and 0.47 &#x000b1; 0.08% injected dose (ID)/g in [<sup>131</sup>I]-FIAU accumulation. The average level of gene expression in the implanted U87-&#x00394;45-TGL tumor was detected as 740 &#x000b1; 47 in fluorescence, 508 &#x000b1; 36 &#x000d7; 10<sup>6</sup> photons/cm<sup>2</sup> per sr in bioluminescence, and 0.86 &#x000b1; 0.06% ID/g in [<sup>131</sup>I]-FIAU accumulation. As a control, the average level of gene expression in the implanted wild-type U87 cells was found at background level in fluorescence or bioluminescence imaging and at 0.03 &#x000b1; 0.01% ID/g in [<sup>131</sup>I]-FIAU accumulation (the background level). After completion of the triple modality imaging, the mice were euthanized and the tissues were harvested for <i>in vitro</i> fluorescence imaging. Bright green fluorescent areas were found in the tumor tissues, demonstrating the presence of TGL labeling.</p></div><div id="TGL.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=%22%20SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20%28dog%20OR%20rabbit%20OR%20pig%20OR%20sheep%29" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="TGL.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=(%20HSV1-tk%20+%20GFP%20+%20luciferase)%20+AND+(primate+non+human)" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="TGL.Human_Studies"><h2 id="_TGL_Human_Studies_">Human Studies</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=(%20HSV1-tk%20+%20GFP%20+%20luciferase)%20+AND+human" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="TGL.references"><h2 id="_TGL_references_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="TGL.REF.1">Massoud T.F. , Singh A. , Gambhir S.S. Noninvasive molecular neuroimaging using reporter genes: part I, principles revisited. <span><span class="ref-journal">AJNR Am J Neuroradiol. </span>2008;<span class="ref-vol">
<strong>29</strong>
</span>(2):229&ndash;34.</span> [<a href="/pmc/articles/PMC8118983/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC8118983</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18024575" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 18024575</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="TGL.REF.2">Gross S. , Piwnica-Worms D. Spying on cancer: molecular imaging in vivo with genetically encoded reporters. <span><span class="ref-journal">Cancer Cell. </span>2005;<span class="ref-vol">
<strong>7</strong>
</span>(1):5&ndash;15.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15652745" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15652745</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="TGL.REF.3">Serganova I. , Ponomarev V. , Blasberg R. Human reporter genes: potential use in clinical studies. <span><span class="ref-journal">Nucl Med Biol. </span>2007;<span class="ref-vol">
<strong>34</strong>
</span>(7):791&ndash;807.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17921031" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 17921031</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="TGL.REF.4">Ponomarev V. , Doubrovin M. , Serganova I. , Vider J. , Shavrin A. , Beresten T. , Ivanova A. , Ageyeva L. , Tourkova V. , Balatoni J. , Bornmann W. , Blasberg R. , Gelovani Tjuvajev J. A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging. <span><span class="ref-journal">Eur J Nucl Med Mol Imaging. </span>2004;<span class="ref-vol">
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</span>(5):740&ndash;51.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15014901" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15014901</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="TGL.REF.5">Wurth C. , Thomas R.M. , Folkers G. , Scapozza L. Folding and self-assembly of herpes simplex virus type 1 thymidine kinase. <span><span class="ref-journal">J Mol Biol. </span>2001;<span class="ref-vol">
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</span>(3):657&ndash;70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11676546" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 11676546</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="TGL.REF.6">Ponomarev V. , Doubrovin M. , Serganova I. , Beresten T. , Vider J. , Shavrin A. , Ageyeva L. , Balatoni J. , Blasberg R. , Tjuvajev J.G. Cytoplasmically retargeted HSV1-tk/GFP reporter gene mutants for optimization of noninvasive molecular-genetic imaging. <span><span class="ref-journal">Neoplasia. </span>2003;<span class="ref-vol">
<strong>5</strong>
</span>(3):245&ndash;54.</span> [<a href="/pmc/articles/PMC1502405/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC1502405</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12869307" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 12869307</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="TGL.REF.7">Kussmann-Gerber S. , Kuonen O. , Folkers G. , Pilger B.D. , Scapozza L. Drug resistance of herpes simplex virus type 1--structural considerations at the molecular level of the thymidine kinase. <span><span class="ref-journal">Eur J Biochem. </span>1998;<span class="ref-vol">
<strong>255</strong>
</span>(2):472&ndash;81.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9716390" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 9716390</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="TGL.REF.8">Chalfie M. , Tu Y. , Euskirchen G. , Ward W.W. , Prasher D.C. Green fluorescent protein as a marker for gene expression. <span><span class="ref-journal">Science. </span>1994;<span class="ref-vol">
<strong>263</strong>
</span>(5148):802&ndash;5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8303295" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 8303295</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="TGL.REF.9">Conti E. , Franks N.P. , Brick P. Crystal structure of firefly luciferase throws light on a superfamily of adenylate-forming enzymes. <span><span class="ref-journal">Structure. </span>1996;<span class="ref-vol">
<strong>4</strong>
</span>(3):287&ndash;98.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8805533" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 8805533</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="TGL.REF.10">Paulmurugan R. , Gambhir S.S. Firefly luciferase enzyme fragment complementation for imaging in cells and living animals. <span><span class="ref-journal">Anal Chem. </span>2005;<span class="ref-vol">
<strong>77</strong>
</span>(5):1295&ndash;302.</span> [<a href="/pmc/articles/PMC4154832/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC4154832</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15732910" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15732910</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="TGL.REF.11">Jacobs A. , Dubrovin M. , Hewett J. , Sena-Esteves M. , Tan C.W. , Slack M. , Sadelain M. , Breakefield X.O. , Tjuvajev J.G. Functional coexpression of HSV-1 thymidine kinase and green fluorescent protein: implications for noninvasive imaging of transgene expression. <span><span class="ref-journal">Neoplasia. </span>1999;<span class="ref-vol">
<strong>1</strong>
</span>(2):154&ndash;61.</span> [<a href="/pmc/articles/PMC1508134/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC1508134</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10933050" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 10933050</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK23131_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Huiming Zhang</span>, PhD<div class="affiliation small">
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD,
<span class="before-email-separator"></span><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><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">October 21, 2008</span>; Last Update: <span itemprop="dateModified">December 1, 2008</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&amp;targetsite=external&amp;targetcat=link&amp;targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Zhang H. HSV1-TK/GFP/Fluc. 2008 Oct 21 [Updated 2008 Dec 1]. 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/sosgreenfluorescencepro2/?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/soshilytefluor647/?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="figobTGLT1"><div id="TGL.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK23131/table/TGL.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__TGL.T1_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Chemical name:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HSV1-TK/GFP/Fluc</td><td rowspan="9" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Abbreviated name:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TGL</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Synonym:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TGL triple reporter</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Agent category:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Protein</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Target:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Target category:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other &#x02013; gene expression</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Method of detection:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Optical imaging, gamma imaging, SPECT</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Source of signal/contrast:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Green fluorescence protein (GFP), firefly luciferase, and <sup>131</sup>I-FIAU</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Activation:</b>
</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;">
<b>Studies:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
<ul class="simple-list"><li class="half_rhythm"><div>
<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" />
<i>In vitro</i>
</div></li></ul>
<ul class="simple-list"><li class="half_rhythm"><div>
<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
</div></li></ul>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No structure is currently available in <a href="http://pubchem.ncbi.nlm.nih.gov" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubChem</a>.</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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