{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T15:00:44Z","timestamp":1761490844690,"version":"3.37.3"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["ME097-PP02, PP07, NM097"],"award-info":[{"award-number":["ME097-PP02, PP07, NM097"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["96-2627-B-400-001"],"award-info":[{"award-number":["96-2627-B-400-001"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transgenic mice harboring imaging reporters take full advantage of imaging technologies in studies using living mice. Here, we established a tri-fusion multimodal reporter gene containing fragments from firefly luciferase, enhanced green fluorescent protein, and herpes simplex virus type 1 thymidine kinase and generated tri-fusion reporter Tg mice. Fibroblast growth factor type 1 (FGF1), a multifunctional mitogen to a wide range of tissues, regulates proliferation of neural stem cells of the brain, where FGF1 expression is initiated through activation of the FGF1B (F1B) promoter. The reporter mouse under the control of the human F1B promoter enables visualization <jats:italic>in vivo<\/jats:italic> where F1B activity is elevated, including tissues not only in the brain but also in the nasopharynx, skull, spine, and testes, particularly in Leydig cells. Treating Tg mice with the alkylating agent busulfan, which is known to eradicate Leydig cells and disrupt spermatogenesis in mice, eliminated the reporter signals. Restoring Leydig cells recovered reporter expression, indicating that the reporter can be used as a surrogate marker for Leydig cells. The F1B tri-fusion reporter mouse model can be utilized in longitudinal monitoring of the health status of the male reproductive system, such as in studies exploring the toxicity of chemicals to spermatogenesis.<\/jats:p>","DOI":"10.1038\/s41598-019-47641-3","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T10:02:32Z","timestamp":1564567352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Tri-fusion Reporter Mouse Reveals Tissue-Specific FGF1B Promoter Activity in vivo"],"prefix":"10.1038","volume":"9","author":[{"given":"Shan-Wen","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2351-2052","authenticated-orcid":false,"given":"Ching-Han","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Ru","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ing-Ming","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-5569","authenticated-orcid":false,"given":"Kurt M.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"47641_CR1","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00330-006-0378-z","volume":"17","author":"C Rome","year":"2007","unstructured":"Rome, C., Couillaud, F. & Moonen, C. T. Gene expression and gene therapy imaging. Eur Radiol 17, 305\u2013319, https:\/\/doi.org\/10.1007\/s00330-006-0378-z (2007).","journal-title":"Eur Radiol"},{"issue":"Suppl 2","key":"47641_CR2","doi-asserted-by":"publisher","first-page":"164S","DOI":"10.2967\/jnumed.107.045955","volume":"49","author":"JH Kang","year":"2008","unstructured":"Kang, J. H. & Chung, J. K. Molecular-genetic imaging based on reporter gene expression. J Nucl Med 49(Suppl 2), 164S\u2013179S, https:\/\/doi.org\/10.2967\/jnumed.107.045955 (2008).","journal-title":"J Nucl Med"},{"key":"47641_CR3","doi-asserted-by":"publisher","first-page":"465","DOI":"10.2310\/7290.2006.00024","volume":"5","author":"AH Kesarwala","year":"2006","unstructured":"Kesarwala, A. H. et al. Second-generation triple reporter for bioluminescence, micro-positron emission tomography, and fluorescence imaging. Mol Imaging 5, 465\u2013474, https:\/\/doi.org\/10.2310\/7290.2006.00024 (2006).","journal-title":"Mol Imaging"},{"key":"47641_CR4","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.mibio.2004.06.009","volume":"6","author":"YJ Kim","year":"2004","unstructured":"Kim, Y. J., Dubey, P., Ray, P., Gambhir, S. S. & Witte, O. N. Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene. Mol Imaging Biol 6, 331\u2013340, https:\/\/doi.org\/10.1016\/j.mibio.2004.06.009 (2004).","journal-title":"Mol Imaging Biol"},{"key":"47641_CR5","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1007\/s00259-003-1441-5","volume":"31","author":"V Ponomarev","year":"2004","unstructured":"Ponomarev, V. et al. A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging. Eur J Nucl Med Mol Imaging 31, 740\u2013751, https:\/\/doi.org\/10.1007\/s00259-003-1441-5 (2004).","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"47641_CR6","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1158\/0008-5472.CAN-03-1816","volume":"64","author":"P Ray","year":"2004","unstructured":"Ray, P., De, A., Min, J. J., Tsien, R. Y. & Gambhir, S. S. Imaging tri-fusion multimodality reporter gene expression in living subjects. Cancer Res 64, 1323\u20131330, https:\/\/doi.org\/10.1158\/0008-5472.CAN-03-1816 (2004).","journal-title":"Cancer Res"},{"key":"47641_CR7","doi-asserted-by":"publisher","first-page":"15292","DOI":"10.1074\/jbc.271.25.15292","volume":"271","author":"DM Ornitz","year":"1996","unstructured":"Ornitz, D. M. et al. Receptor specificity of the fibroblast growth factor family. J Biol Chem 271, 15292\u201315297, https:\/\/doi.org\/10.1074\/jbc.271.25.15292 (1996).","journal-title":"J Biol Chem"},{"key":"47641_CR8","doi-asserted-by":"publisher","first-page":"15694","DOI":"10.1074\/jbc.M601252200","volume":"281","author":"X Zhang","year":"2006","unstructured":"Zhang, X. et al. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem 281, 15694\u201315700, https:\/\/doi.org\/10.1074\/jbc.M601252200 (2006).","journal-title":"J Biol Chem"},{"key":"47641_CR9","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1128\/MCB.9.6.2387","volume":"9","author":"WP Wang","year":"1989","unstructured":"Wang, W. P., Lehtoma, K., Varban, M. L., Krishnan, I. & Chiu, I. M. Cloning of the gene coding for human class 1 heparin-binding growth factor and its expression in fetal tissues. Mol Cell Biol 9, 2387\u20132395 (1989).","journal-title":"Mol Cell Biol"},{"key":"47641_CR10","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1128\/mcb.20.6.2260-2268.2000","volume":"20","author":"DL Miller","year":"2000","unstructured":"Miller, D. L., Ortega, S., Bashayan, O., Basch, R. & Basilico, C. Compensation by fibroblast growth factor 1 (FGF1) does not account for the mild phenotypic defects observed in FGF2 null mice. Mol Cell Biol 20, 2260\u20132268, https:\/\/doi.org\/10.1128\/mcb.20.6.2260-2268.2000 (2000).","journal-title":"Mol Cell Biol"},{"key":"47641_CR11","doi-asserted-by":"publisher","first-page":"211","DOI":"10.2174\/157489006777442478","volume":"1","author":"GJ Chen","year":"2006","unstructured":"Chen, G. J. & Forough, R. Fibroblast growth factors, fibroblast growth factor receptors, diseases, and drugs. Recent Pat Cardiovasc Drug Discov 1, 211\u2013224 (2006).","journal-title":"Recent Pat Cardiovasc Drug Discov"},{"key":"47641_CR12","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.mcn.2009.04.010","volume":"41","author":"DC Lee","year":"2009","unstructured":"Lee, D. C. et al. Isolation of neural stem\/progenitor cells by using EGF\/FGF1 and FGF1B promoter-driven green fluorescence from embryonic and adult mouse brains. Mol Cell Neurosci 41, 348\u2013363, https:\/\/doi.org\/10.1016\/j.mcn.2009.04.010 (2009).","journal-title":"Mol Cell Neurosci"},{"key":"47641_CR13","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1126\/science.7682010","volume":"260","author":"V Nurcombe","year":"1993","unstructured":"Nurcombe, V., Ford, M. D., Wildschut, J. A. & Bartlett, P. F. Developmental regulation of neural response to FGF-1 and FGF-2 by heparan sulfate proteoglycan. Science 260, 103\u2013106, https:\/\/doi.org\/10.1126\/science.7682010 (1993).","journal-title":"Science"},{"key":"47641_CR14","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1046\/j.1440-1711.1998.00762.x","volume":"76","author":"PF Bartlett","year":"1998","unstructured":"Bartlett, P. F. et al. Regulation of neural stem cell differentiation in the forebrain. Immunol Cell Biol 76, 414\u2013418, https:\/\/doi.org\/10.1046\/j.1440-1711.1998.00762.x (1998).","journal-title":"Immunol Cell Biol"},{"key":"47641_CR15","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.ydbio.2006.05.031","volume":"296","author":"AL Jacob","year":"2006","unstructured":"Jacob, A. L., Smith, C., Partanen, J. & Ornitz, D. M. Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation. Dev Biol 296, 315\u2013328, https:\/\/doi.org\/10.1016\/j.ydbio.2006.05.031 (2006).","journal-title":"Dev Biol"},{"key":"47641_CR16","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1083\/jcb.114.6.1261","volume":"114","author":"YM Fu","year":"1991","unstructured":"Fu, Y. M. et al. Acidic fibroblast growth factor in the developing rat embryo. J Cell Biol 114, 1261\u20131273, https:\/\/doi.org\/10.1083\/jcb.114.6.1261 (1991).","journal-title":"J Cell Biol"},{"key":"47641_CR17","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/0045-6039(88)90010-3","volume":"22","author":"H Grunz","year":"1988","unstructured":"Grunz, H., McKeehan, W. L., Knochel, W., Born, J. & Tiedemann, H. Induction of mesodermal tissues by acidic and basic heparin binding growth factors. Cell Differ 22, 183\u2013189, https:\/\/doi.org\/10.1016\/0045-6039(88)90010-3 (1988).","journal-title":"Cell Differ"},{"key":"47641_CR18","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/nar\/21.3.489","volume":"21","author":"RA Payson","year":"1993","unstructured":"Payson, R. A. et al. Cloning of two novel forms of human acidic fibroblast growth factor (aFGF) mRNA. Nucleic Acids Res 21, 489\u2013495, https:\/\/doi.org\/10.1093\/nar\/21.3.489 (1993).","journal-title":"Nucleic Acids Res"},{"key":"47641_CR19","first-page":"341","volume":"8","author":"RL Myers","year":"1993","unstructured":"Myers, R. L., Payson, R. A., Chotani, M. A., Deaven, L. L. & Chiu, I. M. Gene structure and differential expression of acidic fibroblast growth factor mRNA: identification and distribution of four different transcripts. Oncogene 8, 341\u2013349 (1993).","journal-title":"Oncogene"},{"key":"47641_CR20","first-page":"785","volume":"11","author":"RL Myers","year":"1995","unstructured":"Myers, R. L., Chedid, M., Tronick, S. R. & Chiu, I. M. Different fibroblast growth factor 1 (FGF-1) transcripts in neural tissues, glioblastomas and kidney carcinoma cell lines. Oncogene 11, 785\u2013789 (1995).","journal-title":"Oncogene"},{"key":"47641_CR21","doi-asserted-by":"publisher","first-page":"8257","DOI":"10.1074\/jbc.270.14.8257","volume":"270","author":"RL Myers","year":"1995","unstructured":"Myers, R. L., Ray, S. K., Eldridge, R., Chotani, M. A. & Chiu, I. M. Functional characterization of the brain-specific FGF-1 promoter, FGF-1.B. J Biol Chem 270, 8257\u20138266, https:\/\/doi.org\/10.1074\/jbc.270.14.8257 (1995).","journal-title":"J Biol Chem"},{"key":"47641_CR22","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1093\/nar\/23.3.434","volume":"23","author":"MA Chotani","year":"1995","unstructured":"Chotani, M. A., Payson, R. A., Winkles, J. A. & Chiu, I. M. Human fibroblast growth factor 1 gene expression in vascular smooth muscle cells is modulated via an alternate promoter in response to serum and phorbol ester. Nucleic Acids Res 23, 434\u2013441, https:\/\/doi.org\/10.1093\/nar\/23.3.434 (1995).","journal-title":"Nucleic Acids Res"},{"key":"47641_CR23","doi-asserted-by":"publisher","first-page":"30263","DOI":"10.1074\/jbc.271.47.30263","volume":"271","author":"KY Alam","year":"1996","unstructured":"Alam, K. Y. et al. Characterization of the 1B promoter of fibroblast growth factor 1 and its expression in the adult and developing mouse brain. J Biol Chem 271, 30263\u201330271, https:\/\/doi.org\/10.1074\/jbc.271.47.30263 (1996).","journal-title":"J Biol Chem"},{"key":"47641_CR24","doi-asserted-by":"publisher","first-page":"6229","DOI":"10.1038\/sj.onc.1204021","volume":"19","author":"IM Chiu","year":"2000","unstructured":"Chiu, I. M., Touhalisky, K., Liu, Y., Yates, A. & Frostholm, A. Tumorigenesis in transgenic mice in which the SV40 T antigen is driven by the brain-specific FGF1 promoter. Oncogene 19, 6229\u20136239, https:\/\/doi.org\/10.1038\/sj.onc.1204021 (2000).","journal-title":"Oncogene"},{"key":"47641_CR25","doi-asserted-by":"publisher","first-page":"7453","DOI":"10.1038\/sj.onc.1205936","volume":"21","author":"WA Weiss","year":"2002","unstructured":"Weiss, W. A. et al. Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum. Oncogene 21, 7453\u20137463, https:\/\/doi.org\/10.1038\/sj.onc.1205936 (2002).","journal-title":"Oncogene"},{"key":"47641_CR26","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1002\/dvdy.21753","volume":"238","author":"YC Hsu","year":"2009","unstructured":"Hsu, Y. C. et al. Brain-specific 1B promoter of FGF1 gene facilitates the isolation of neural stem\/progenitor cells with self-renewal and multipotent capacities. Dev Dyn 238, 302\u2013314, https:\/\/doi.org\/10.1002\/dvdy.21753 (2009).","journal-title":"Dev Dyn"},{"key":"47641_CR27","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/dneu.22225","volume":"75","author":"MS Chen","year":"2015","unstructured":"Chen, M. S. et al. Human FGF1 promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFP transgenic mice. Developmental neurobiology 75, 232\u2013248, https:\/\/doi.org\/10.1002\/dneu.22225 (2015).","journal-title":"Developmental neurobiology"},{"key":"47641_CR28","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s11307-008-0147-2","volume":"10","author":"KM Lin","year":"2008","unstructured":"Lin, K. M., Hsu, C. H., Chang, W. S., Chen, C. T. & Lee, T. W. Human breast tumor cells express multimodal imaging reporter genes. Mol Imaging Biol 10, 253\u2013263, https:\/\/doi.org\/10.1007\/s11307-008-0147-2 (2008).","journal-title":"Mol Imaging Biol"},{"key":"47641_CR29","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1038\/nprot.2006.334","volume":"1","author":"SS Yaghoubi","year":"2006","unstructured":"Yaghoubi, S. S. & Gambhir, S. S. Measuring herpes simplex virus thymidine kinase reporter gene expression in vitro. Nature protocols 1, 2137\u20132142, https:\/\/doi.org\/10.1038\/nprot.2006.334 (2006).","journal-title":"Nature protocols"},{"key":"47641_CR30","doi-asserted-by":"publisher","first-page":"e73580","DOI":"10.1371\/journal.pone.0073580","volume":"8","author":"X Yan","year":"2013","unstructured":"Yan, X. et al. A transgenic tri-modality reporter mouse. Plos one 8, e73580, https:\/\/doi.org\/10.1371\/journal.pone.0073580 (2013).","journal-title":"Plos one"},{"key":"47641_CR31","doi-asserted-by":"publisher","first-page":"S191","DOI":"10.1016\/j.ymthe.2006.08.564","volume":"13","author":"H Fu","year":"2006","unstructured":"Fu, H., DiRosario, J. & McCarty, D. M. Optimizing the Mannitol-Facilitated CNS Entry of Peripherally-Delivered AAV2 Vector. Mol Therapy 13, S191, https:\/\/doi.org\/10.1016\/j.ymthe.2006.08.564 (2006).","journal-title":"Mol Therapy"},{"key":"47641_CR32","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/sj.gt.3302961","volume":"14","author":"H Fu","year":"2007","unstructured":"Fu, H. et al. Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice. Gene Ther 14, 1065\u20131077, https:\/\/doi.org\/10.1038\/sj.gt.3302961 (2007).","journal-title":"Gene Ther"},{"key":"47641_CR33","unstructured":"Tong, R., Ray, P. & Gambhir, S. In World Molecular Imaging Conference 0911 (Nice, France, 2008)."},{"key":"47641_CR34","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/nature10998","volume":"485","author":"JW Jonker","year":"2012","unstructured":"Jonker, J. W. et al. A PPARgamma-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis. Nature 485, 391\u2013394, https:\/\/doi.org\/10.1038\/nature10998 (2012).","journal-title":"Nature"},{"key":"47641_CR35","doi-asserted-by":"publisher","first-page":"11937","DOI":"10.1074\/jbc.274.17.11937","volume":"274","author":"F Madiai","year":"1999","unstructured":"Madiai, F., Hackshaw, K. V. & Chiu, I. M. Characterization of the entire transcription unit of the mouse fibroblast growth factor 1 (FGF-1) gene. Tissue-specific expression of the FGF-1.A mRNA. The Journal of biological chemistry 274, 11937\u201311944, https:\/\/doi.org\/10.1074\/jbc.274.17.11937 (1999).","journal-title":"The Journal of biological chemistry"},{"key":"47641_CR36","doi-asserted-by":"publisher","first-page":"2853","DOI":"10.1089\/scd.2015.0157","volume":"24","author":"L Hung-Yu","year":"2015","unstructured":"Hung-Yu, L., Don-Ching, L., Horng-Dar, W., Ya-Hui, C. & Ing-Ming, C. Activation of FGF1B Promoter and FGF1 Are Involved in Cardiogenesis Through the Signaling of PKC, but Not MAPK. Stem Cells and Development 24, 2853\u20132863, https:\/\/doi.org\/10.1089\/scd.2015.0157 (2015).","journal-title":"Stem Cells and Development"},{"key":"47641_CR37","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1095\/biolreprod65.3.660","volume":"65","author":"SM Mendis-Handagama","year":"2001","unstructured":"Mendis-Handagama, S. M. & Ariyaratne, H. B. Differentiation of the adult Leydig cell population in the postnatal testis. Biol Reprod 65, 660\u2013671, https:\/\/doi.org\/10.1095\/biolreprod65.3.660 (2001).","journal-title":"Biol Reprod"},{"key":"47641_CR38","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1083\/jcb.200409107","volume":"167","author":"MS Davidoff","year":"2004","unstructured":"Davidoff, M. S. et al. Progenitor cells of the testosterone-producing Leydig cells revealed. J Cell Biol 167, 935\u2013944, https:\/\/doi.org\/10.1083\/jcb.200409107 (2004).","journal-title":"J Cell Biol"},{"key":"47641_CR39","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1073\/pnas.0507692103","volume":"103","author":"RS Ge","year":"2006","unstructured":"Ge, R. S. et al. In search of rat stem Leydig cells: identification, isolation, and lineage-specific development. Proc Natl Acad Sci USA 103, 2719\u20132724, https:\/\/doi.org\/10.1073\/pnas.0507692103 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"47641_CR40","first-page":"1682","volume":"42","author":"MM Alauddin","year":"2001","unstructured":"Alauddin, M. M., Shahinian, A., Gordon, E. M., Bading, J. R. & Conti, P. S. Preclinical evaluation of the penciclovir analog 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine for in vivo measurement of suicide gene expression with PET. J Nucl Med 42, 1682\u20131690 (2001).","journal-title":"J Nucl Med"},{"key":"47641_CR41","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/jlcr.637","volume":"46","author":"MM Alauddin","year":"2003","unstructured":"Alauddin, M. M., Conti, P. S. & Fissekis, J. D. A general synthesis of 2\u2032-deoxy-2\u2032-[18F]fluoro-1-b-D-arabinofuranosyluracil and its 5-substituted nucleosides. J Label Compd Radiopharm 46, 285\u2013289, https:\/\/doi.org\/10.1002\/jlcr.637 (2003).","journal-title":"J Label Compd Radiopharm"},{"key":"47641_CR42","doi-asserted-by":"publisher","first-page":"6101","DOI":"10.1158\/0008-5472.CAN-04-0842","volume":"64","author":"I Serganova","year":"2004","unstructured":"Serganova, I. et al. Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. Cancer Res 64, 6101\u20136108, https:\/\/doi.org\/10.1158\/0008-5472.CAN-04-0842 (2004).","journal-title":"Cancer Res"},{"key":"47641_CR43","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1088\/0031-9155\/43\/4\/027","volume":"43","author":"J Qi","year":"1998","unstructured":"Qi, J., Leahy, R. M., Cherry, S. R., Chatziioannou, A. & Farquhar, T. H. High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner. Phys Med Biol 43, 1001\u20131013 (1998).","journal-title":"Phys Med Biol"},{"key":"47641_CR44","unstructured":"Ruangma, A., Laforest, R., Bai, B. & Leahy, R. M.\u00a0Characterization of USC-MAP image reconstruction on microPET-R4\u00ae.\u00a0IEEE Nucl. Sci. Symp. Conf. 3449\u20133453 (2004)."},{"key":"47641_CR45","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1162\/153535003322556877","volume":"2","author":"AM Loening","year":"2003","unstructured":"Loening, A. M. & Gambhir, S. S. AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2, 131\u2013137 (2003).","journal-title":"Mol Imaging"},{"key":"47641_CR46","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00259-003-1269-z","volume":"31","author":"WP Deng","year":"2004","unstructured":"Deng, W. P. et al. Non-invasive in vivo imaging with radiolabelled FIAU for monitoring cancer gene therapy using herpes simplex virus type 1 thymidine kinase and ganciclovir. Eur J Nucl Med Mol Imaging 31, 99\u2013109, https:\/\/doi.org\/10.1007\/s00259-003-1269-z (2004).","journal-title":"Eur J Nucl Med Mol Imaging"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47641-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47641-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47641-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T12:11:25Z","timestamp":1671279085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47641-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,31]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["47641"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-47641-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2019,7,31]]},"assertion":[{"value":"28 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"I.C. and K.L. were granted US patents 12\/460797 and #13\/359424 regarding the F1B-TMIR vector and the uses of F1B-TMIR transgenic mice. I.C. and K.L. have no other competing interests. All other authors declare no potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"11143"}}