{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:06:53Z","timestamp":1784606813185,"version":"3.55.0"},"reference-count":93,"publisher":"Springer Science and Business Media LLC","issue":"7-8","license":[{"start":{"date-parts":[[2020,7,4]],"date-time":"2020-07-04T00:00:00Z","timestamp":1593820800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,7,4]],"date-time":"2020-07-04T00:00:00Z","timestamp":1593820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772010"],"award-info":[{"award-number":["81772010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Apoptosis"],"published-print":{"date-parts":[[2020,8]]},"DOI":"10.1007\/s10495-020-01621-5","type":"journal-article","created":{"date-parts":[[2020,7,4]],"date-time":"2020-07-04T13:03:41Z","timestamp":1593867821000},"page":"459-473","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Rational design of genetically encoded reporter genes for optical imaging of apoptosis"],"prefix":"10.1007","volume":"25","author":[{"given":"Zhijing","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhuang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-0833","authenticated-orcid":false,"given":"Fu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,4]]},"reference":[{"key":"1621_CR1","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.2967\/jnumed.110.078584","volume":"51","author":"G Niu","year":"2010","unstructured":"Niu G, Chen X (2010) Apoptosis imaging: beyond annexin V. J Nucl Med 51:1659\u20131662","journal-title":"J Nucl Med"},{"key":"1621_CR2","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1007\/s13738-017-1178-x","volume":"14","author":"CH Xia","year":"2017","unstructured":"Xia CH, Lun ZQ, Lin XY, Wang BQ, Wang Y (2017) Apoptosis imaging by radionuclide probes. J Iran Chem Soc 14:2437\u20132447","journal-title":"J Iran Chem Soc"},{"key":"1621_CR3","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nrc2663","volume":"9","author":"TG Cotter","year":"2009","unstructured":"Cotter TG (2009) Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer 9:501\u2013507","journal-title":"Nat Rev Cancer"},{"key":"1621_CR4","doi-asserted-by":"crossref","first-page":"20476","DOI":"10.18632\/oncotarget.14730","volume":"8","author":"X Wang","year":"2017","unstructured":"Wang X, Feng H, Zhao S et al (2017) SPECT and PET radiopharmaceuticals for molecular imaging of apoptosis: from bench to clinic. Oncotarget 8:20476\u201320495","journal-title":"Oncotarget"},{"key":"1621_CR5","doi-asserted-by":"crossref","first-page":"559","DOI":"10.7150\/thno.11548","volume":"5","author":"WB Zeng","year":"2015","unstructured":"Zeng WB, Wang XB, Xu PF, Liu G, Eden HS, Chen XY (2015) Molecular imaging of apoptosis: from micro to macro. Theranostics 5:559\u2013582","journal-title":"Theranostics"},{"key":"1621_CR6","first-page":"3","volume":"1","author":"X Huang","year":"2011","unstructured":"Huang X, Lee S, Chen X (2011) Design of \u201csmart\u201d probes for optical imaging of apoptosis. Am J Nucl Med Mol Imaging 1:3\u201317","journal-title":"Am J Nucl Med Mol Imaging"},{"key":"1621_CR7","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.cell.2005.05.019","volume":"121","author":"DR Green","year":"2005","unstructured":"Green DR (2005) Apoptotic pathways: ten minutes to dead. Cell 121:671\u2013674","journal-title":"Cell"},{"key":"1621_CR8","first-page":"15","volume":"22","author":"S Gupta","year":"2003","unstructured":"Gupta S (2003) Molecular signaling in death receptor and mitochondrial pathways of apoptosis. Int J Oncol 22:15\u201320","journal-title":"Int J Oncol"},{"key":"1621_CR9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.coi.2019.11.009","volume":"62","author":"S Nagata","year":"2020","unstructured":"Nagata S, Sakuragi T, Segawa K (2020) Flippase and scramblase for phosphatidylserine exposure. Curr Opin Immunol 62:31\u201338","journal-title":"Curr Opin Immunol"},{"key":"1621_CR10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1006\/excr.2000.4834","volume":"256","author":"S Nagata","year":"2000","unstructured":"Nagata S (2000) Apoptotic DNA fragmentation. Exp Cell Res 256:12\u201318","journal-title":"Exp Cell Res"},{"key":"1621_CR11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/34112","volume":"391","author":"M Enari","year":"1998","unstructured":"Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391:43\u201350","journal-title":"Nature"},{"key":"1621_CR12","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0092-8674(00)80197-X","volume":"89","author":"X Liu","year":"1997","unstructured":"Liu X, Zou H, Slaughter C, Wang X (1997) DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89:175\u2013184","journal-title":"Cell"},{"key":"1621_CR13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/35083620","volume":"412","author":"LY Li","year":"2001","unstructured":"Li LY, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95\u201399","journal-title":"Nature"},{"key":"1621_CR14","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/35037710","volume":"407","author":"MO Hengartner","year":"2000","unstructured":"Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770\u2013776","journal-title":"Nature"},{"key":"1621_CR15","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/cdd.2011.96","volume":"19","author":"L Galluzzi","year":"2012","unstructured":"Galluzzi L, Vitale I, Abrams J et al (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ 19:107\u2013120","journal-title":"Cell Death Differ"},{"key":"1621_CR16","doi-asserted-by":"crossref","unstructured":"Ormerod M (1998) The study of apoptotic cells by flow cytometry. Leukemia.","DOI":"10.1038\/sj.leu.2401061"},{"key":"1621_CR17","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/978-1-4939-3302-0_15","volume":"1389","author":"AM Rieger","year":"2016","unstructured":"Rieger AM, Barreda DR (2016) Accurate assessment of cell death by imaging flow cytometry. Methods Mol Biol 1389:209\u2013220","journal-title":"Methods Mol Biol"},{"key":"1621_CR18","doi-asserted-by":"crossref","unstructured":"Mountz JD, Hsu HC, Wu Q, Liu HG, Zhang HG, Mountz JM (2002) Molecular imaging: new applications for biochemistry. J Cell Biochem 162\u2013171.","DOI":"10.1002\/jcb.10434"},{"key":"1621_CR19","doi-asserted-by":"crossref","first-page":"W206","DOI":"10.2214\/AJR.13.10555","volume":"201","author":"H Youn","year":"2013","unstructured":"Youn H, Chung JK (2013) Reporter gene imaging. Am J Roentgenol 201:W206\u2013214","journal-title":"Am J Roentgenol"},{"issue":"Suppl 2","key":"1621_CR20","doi-asserted-by":"crossref","first-page":"164S","DOI":"10.2967\/jnumed.107.045955","volume":"49","author":"JH Kang","year":"2008","unstructured":"Kang JH, Chung JK (2008) Molecular-genetic imaging based on reporter gene expression. J Nucl Med 49(Suppl 2):164S\u2013179S","journal-title":"J Nucl Med"},{"key":"1621_CR21","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.2967\/jnumed.118.220004","volume":"60","author":"I Serganova","year":"2019","unstructured":"Serganova I, Blasberg RG (2019) Molecular imaging with reporter genes: has its promise been delivered? J Nucl Med 60:1665\u20131681","journal-title":"J Nucl Med"},{"key":"1621_CR22","doi-asserted-by":"crossref","first-page":"12288","DOI":"10.1073\/pnas.0404041101","volume":"101","author":"KE Luker","year":"2004","unstructured":"Luker KE, Smith MC, Luker GD, Gammon ST, Piwnica-Worms H, Piwnica-Worms D (2004) Kinetics of regulated protein\u2013protein interactions revealed with firefly luciferase complementation imaging in cells and living animals. Proc Natl Acad Sci USA 101:12288\u201312293","journal-title":"Proc Natl Acad Sci USA"},{"key":"1621_CR23","first-page":"2109","volume":"45","author":"JH Shin","year":"2004","unstructured":"Shin JH, Chung JK, Kang JH et al (2004) Noninvasive imaging for monitoring of viable cancer cells using a dual-imaging reporter gene. J Nucl Med 45:2109\u20132115","journal-title":"J Nucl Med"},{"key":"1621_CR24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/156652312799789299","volume":"12","author":"M Tangney","year":"2012","unstructured":"Tangney M, Francis KP (2012) In vivo optical imaging in gene & cell therapy. Curr Gene Ther 12:2\u201311","journal-title":"Curr Gene Ther"},{"key":"1621_CR25","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1152\/physrev.00038.2009","volume":"90","author":"M Dmitriy","year":"2010","unstructured":"Dmitriy M, Chudakov MVM, Lukyanov S, Lukyanov KA (2010) Fluorescent proteins and their applications in imaging living cells and tissues. Physiol Rev 90:1103\u20131163","journal-title":"Physiol Rev"},{"key":"1621_CR26","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.tibtech.2005.10.005","volume":"23","author":"DM Chudakov","year":"2005","unstructured":"Chudakov DM, Lukyanov S, Lukyanov KA (2005) Fluorescent proteins as a toolkit for in vivo imaging. Trends Biotechnol 23:605\u2013613","journal-title":"Trends Biotechnol"},{"key":"1621_CR27","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/jcp.1030590302","volume":"59","author":"O Shimomura","year":"1962","unstructured":"Shimomura O, Johnson FH, Saiga Y (1962) Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan. J Cell Comp Physiol 59:223\u2013239","journal-title":"J Cell Comp Physiol"},{"key":"1621_CR28","doi-asserted-by":"crossref","unstructured":"Zhang J, Wang X, Cui W et al (2013) Visualization of caspase-3-like activity in cells using a genetically encoded fluorescent biosensor activated by protein cleavage. Nat Commun 4","DOI":"10.1038\/ncomms3157"},{"key":"1621_CR29","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1073\/pnas.1502857112","volume":"112","author":"TL To","year":"2015","unstructured":"To TL, Piggott BJ, Makhijani K, Yu D, Jan YN, Shu X (2015) Rationally designed fluorogenic protease reporter visualizes spatiotemporal dynamics of apoptosis in vivo. Proc Natl Acad Sci USA 112:3338\u20133343","journal-title":"Proc Natl Acad Sci USA"},{"key":"1621_CR30","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.chembiol.2016.06.007","volume":"23","author":"TL To","year":"2016","unstructured":"To TL, Schepis A, Ruiz-Gonzalez R et al (2016) Rational design of a GFP-based fluorogenic caspase reporter for imaging apoptosis in vivo. Cell Chem Biol 23:875\u2013882","journal-title":"Cell Chem Biol"},{"key":"1621_CR31","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.1021\/jacs.8b13042","volume":"141","author":"Q Zhang","year":"2019","unstructured":"Zhang Q, Schepis A, Huang H et al (2019) Designing a green fluorogenic protease reporter by flipping a beta strand of GFP for imaging apoptosis in animals. J Am Chem Soc 141:4526\u20134530","journal-title":"J Am Chem Soc"},{"key":"1621_CR32","doi-asserted-by":"crossref","first-page":"e166","DOI":"10.1038\/cddis.2011.47","volume":"2","author":"N Yivgi-Ohana","year":"2011","unstructured":"Yivgi-Ohana N, Eifer M, Addadi Y, Neeman M, Gross A (2011) Utilizing mitochondrial events as biomarkers for imaging apoptosis. Cell Death Dis 2:e166","journal-title":"Cell Death Dis"},{"key":"1621_CR33","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1021\/acs.analchem.5b03367","volume":"88","author":"Y Nasu","year":"2015","unstructured":"Nasu Y, Asaoka Y, Namae M, Nishina H, Yoshimura H, Ozawa T (2015) Genetically encoded fluorescent probe for imaging apoptosis in vivo with spontaneous GFP complementation. Anal Chem 88:838\u2013844","journal-title":"Anal Chem"},{"key":"1621_CR34","doi-asserted-by":"crossref","unstructured":"Nicholls SB, Chu J, Abbruzzese G, Tremblay KD, Hardy JA. (2011) Mechanism of a genetically encoded dark-to-bright reporter for caspase activity. J Biol Chem","DOI":"10.1074\/jbc.M111.221648"},{"key":"1621_CR35","doi-asserted-by":"crossref","first-page":"015001","DOI":"10.1088\/2050-6120\/aae6f8","volume":"7","author":"LA Balderstone","year":"2018","unstructured":"Balderstone LA, Dawson JC, Welman A, Serrels A, Wedge SR, Brunton VG (2018) Development of a fluorescence-based cellular apoptosis reporter. Methods Appl Fluoresc 7:015001","journal-title":"Methods Appl Fluoresc"},{"key":"1621_CR36","doi-asserted-by":"crossref","first-page":"13901","DOI":"10.1073\/pnas.0806983105","volume":"105","author":"PL Bardet","year":"2008","unstructured":"Bardet PL, Kolahgar G, Mynett A et al (2008) A fluorescent reporter of caspase activity for live imaging. Proc Natl Acad Sci USA 105:13901\u201313905","journal-title":"Proc Natl Acad Sci USA"},{"key":"1621_CR37","doi-asserted-by":"crossref","first-page":"4336","DOI":"10.1096\/fj.10-161018","volume":"24","author":"TJ van Ham","year":"2010","unstructured":"van Ham TJ, Mapes J, Kokel D, Peterson RT (2010) Live imaging of apoptotic cells in zebrafish. FASEB J 24:4336\u20134342","journal-title":"FASEB J"},{"key":"1621_CR38","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1172\/JCI34388","volume":"118","author":"B Breart","year":"2008","unstructured":"Breart B, Lema\u00eetre F, Celli S, Bousso P (2008) Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice. J Clin Invest 118:1390\u20131397","journal-title":"J Clin Invest"},{"key":"1621_CR39","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/j.celrep.2012.10.015","volume":"2","author":"R Garrod Kym","year":"2012","unstructured":"Garrod Kym R, Moreau H\u00e9l\u00e8ne D, Garcia Z et al (2012) Dissecting T cell contraction in vivo using a genetically encoded reporter of apoptosis. Cell Rep 2:1438\u20131447","journal-title":"Cell Rep"},{"key":"1621_CR40","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0006-291X(03)00559-X","volume":"304","author":"KQ Luo","year":"2003","unstructured":"Luo KQ, Vivian CY, Pu Y, Chang DC (2003) Measuring dynamics of caspase-8 activation in a single living HeLa cell during TNF\u03b1-induced apoptosis. Biochem Biophys Res Commun 304:217\u2013222","journal-title":"Biochem Biophys Res Commun"},{"key":"1621_CR41","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1083\/jcb.200207111","volume":"160","author":"K Takemoto","year":"2003","unstructured":"Takemoto K, Nagai T, Miyawaki A, Miura M (2003) Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects. J Cell Biol 160:235\u2013243","journal-title":"J Cell Biol"},{"key":"1621_CR42","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11307-009-0235-y","volume":"12","author":"F Zhou","year":"2010","unstructured":"Zhou F, Xing D, Wu S, Chen WR (2010) Intravital imaging of tumor apoptosis with FRET probes during tumor therapy. Mol Imag Biol 12:63\u201370","journal-title":"Mol Imag Biol"},{"key":"1621_CR43","doi-asserted-by":"crossref","first-page":"13367","DOI":"10.1073\/pnas.0702733104","volume":"104","author":"K Takemoto","year":"2007","unstructured":"Takemoto K, Kuranaga E, Tonoki A, Nagai T, Miyawaki A, Miura M (2007) Local initiation of caspase activation in Drosophila salivary gland programmed cell death in vivo. Proc Natl Acad Sci USA 104:13367\u201313372","journal-title":"Proc Natl Acad Sci USA"},{"key":"1621_CR44","doi-asserted-by":"crossref","first-page":"729","DOI":"10.4161\/cc.5.7.2630","volume":"5","author":"Y Wu","year":"2006","unstructured":"Wu Y, Xing D, Chen WR (2006) Single cell FRET imaging for determination of pathway of tumor cell apoptosis induced by photofrin-PDT. Cell Cycle 5:729\u2013734","journal-title":"Cell Cycle"},{"key":"1621_CR45","doi-asserted-by":"crossref","unstructured":"Mayer CT, Gazumyan A, Kara EE et al (2017) The microanatomic segregation of selection by apoptosis in the germinal center. Science (New York, NY) 358.","DOI":"10.1126\/science.aao2602"},{"key":"1621_CR46","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1254\/jphs.FP0040592","volume":"97","author":"H Kawai","year":"2005","unstructured":"Kawai H, Suzuki T, Kobayashi T et al (2005) Simultaneous real-time detection of initiator-and effector-caspase activation by double fluorescence resonance energy transfer analysis. J Pharmacol Sci 97:361\u2013368","journal-title":"J Pharmacol Sci"},{"key":"1621_CR47","doi-asserted-by":"crossref","first-page":"024011","DOI":"10.1117\/1.2187013","volume":"11","author":"J Lin","year":"2006","unstructured":"Lin J, Zhang Z, Yang J, Zeng S, Liu B, Luo Q (2006) Real-time detection of caspase-2 activation in a single living HeLa cell during cisplatin-induced apoptosis. J Biomed Opt 11:024011","journal-title":"J Biomed Opt"},{"key":"1621_CR48","doi-asserted-by":"crossref","first-page":"e50218","DOI":"10.1371\/journal.pone.0050218","volume":"7","author":"K Kominami","year":"2012","unstructured":"Kominami K, Nagai T, Sawasaki T et al (2012) In vivo imaging of hierarchical spatiotemporal activation of caspase-8 during apoptosis. PLoS ONE 7:e50218","journal-title":"PLoS ONE"},{"key":"1621_CR49","doi-asserted-by":"crossref","unstructured":"Buschhaus JM, Humphries B, Luker KE, Luker GD. (2018) A caspase-3 reporter for fluorescence lifetime imaging of single-cell apoptosis. Cells 7.","DOI":"10.3390\/cells7060057"},{"key":"1621_CR50","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/btpr.144","volume":"25","author":"ST Gammon","year":"2009","unstructured":"Gammon ST, Villalobos VM, Roshal M, Samrakandi M, Piwnica-Worms D (2009) Rational design of novel red-shifted BRET pairs: platforms for real-time single-chain protease biosensors. Biotechnol Prog 25:559\u2013569","journal-title":"Biotechnol Prog"},{"key":"1621_CR51","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1002\/cbic.201700486","volume":"18","author":"S Tsuboi","year":"2017","unstructured":"Tsuboi S, Jin T (2017) Bioluminescence resonance energy transfer (BRET)-coupled AnnexinV-functionalized quantum dots for near-infrared optical detection of apoptotic cells. ChemBioChem 18:2231\u20132235","journal-title":"ChemBioChem"},{"key":"1621_CR52","doi-asserted-by":"crossref","first-page":"26248","DOI":"10.1074\/jbc.M412327200","volume":"280","author":"JA Sniegowski","year":"2005","unstructured":"Sniegowski JA, Lappe JW, Patel HN, Huffman HA, Wachter RM (2005) Base catalysis of chromophore formation in Arg96 and Glu222 variants of green fluorescent protein. J Biol Chem 280:26248\u201326255","journal-title":"J Biol Chem"},{"key":"1621_CR53","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/pro.2188","volume":"22","author":"SB Nicholls","year":"2013","unstructured":"Nicholls SB, Hardy JA (2013) Structural basis of fluorescence quenching in caspase activatable-GFP. Protein Sci 22:247\u2013257","journal-title":"Protein Sci"},{"key":"1621_CR54","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/j.bpj.2013.01.058","volume":"104","author":"P Wu","year":"2013","unstructured":"Wu P, Nicholls SB, Hardy JA (2013) A tunable, modular approach to fluorescent protease-activated reporters. Biophys J 104:1605\u20131614","journal-title":"Biophys J"},{"key":"1621_CR55","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev.biochem.67.1.509","volume":"67","author":"RY Tsien","year":"1998","unstructured":"Tsien RY (1998) The green fluorescent protein. Annu Rev Biochem 67:509\u2013544","journal-title":"Annu Rev Biochem"},{"key":"1621_CR56","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nprot.2011.364","volume":"6","author":"Y Sun","year":"2011","unstructured":"Sun Y, Day RN, Periasamy A (2011) Investigating protein-protein interactions in living cells using fluorescence lifetime imaging microscopy. Nat Protoc 6:1324\u20131340","journal-title":"Nat Protoc"},{"key":"1621_CR57","doi-asserted-by":"crossref","unstructured":"Buschhaus JM, Gibbons AE, Luker KE, Luker GD (2017) Fluorescence lifetime imaging of a caspase-3 apoptosis reporter. Curr Protocols Cell Biol 77:21.12.21\u201321.12.12.","DOI":"10.1002\/cpcb.36"},{"key":"1621_CR58","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/84443","volume":"19","author":"AG Harpur","year":"2001","unstructured":"Harpur AG, Wouters FS, Bastiaens PI (2001) Imaging FRET between spectrally similar GFP molecules in single cells. Nat Biotechnol 19:167\u2013169","journal-title":"Nat Biotechnol"},{"key":"1621_CR59","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-anchem-061318-115027","volume":"12","author":"H-W Yeh","year":"2019","unstructured":"Yeh H-W, Ai H-W (2019) Development and applications of bioluminescent and chemiluminescent reporters and biosensors. Annu Rev Analyt Chem 12:129\u2013150","journal-title":"Annu Rev Analyt Chem"},{"key":"1621_CR60","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.tibtech.2017.03.012","volume":"35","author":"L Mezzanotte","year":"2017","unstructured":"Mezzanotte L, van\u2019t Root M, Karatas H, Goun EA, L\u00f6wik CW (2017) In vivo molecular bioluminescence imaging: new tools and applications. Trends Biotechnol 35:640\u2013652","journal-title":"Trends Biotechnol"},{"key":"1621_CR61","doi-asserted-by":"crossref","first-page":"15608","DOI":"10.1073\/pnas.242594299","volume":"99","author":"R Paulmurugan","year":"2002","unstructured":"Paulmurugan R, Umezawa Y, Gambhir S (2002) Noninvasive imaging of protein\u2013protein interactions in living subjects by using reporter protein complementation and reconstitution strategies. Proc Natl Acad Sci USA 99:15608\u201315613","journal-title":"Proc Natl Acad Sci USA"},{"key":"1621_CR62","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.bios.2012.06.034","volume":"38","author":"M Torkzadeh-Mahani","year":"2012","unstructured":"Torkzadeh-Mahani M, Ataei F, Nikkhah M, Hosseinkhani S (2012) Design and development of a whole-cell luminescent biosensor for detection of early-stage of apoptosis. Biosensors Bioelectron 38:362\u2013368","journal-title":"Biosensors Bioelectron"},{"issue":"346\u2013350","key":"1621_CR63","first-page":"352","volume":"34","author":"D Thormeyer","year":"2003","unstructured":"Thormeyer D, Ammerpohl O, Larsson O et al (2003) Characterization of lacZ complementation deletions using membrane receptor dimerization. Biotechniques 34(346\u2013350):352\u2013345","journal-title":"Biotechniques"},{"key":"1621_CR64","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1158\/1078-0432.CCR-07-0782","volume":"14","author":"JM Coppola","year":"2008","unstructured":"Coppola JM, Ross BD, Rehemtulla A (2008) Noninvasive imaging of apoptosis and its application in cancer therapeutics. Clin Cancer Res 14:2492\u20132501","journal-title":"Clin Cancer Res"},{"key":"1621_CR65","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1096\/fj.13-243014","volume":"28","author":"HW Lee","year":"2014","unstructured":"Lee HW, Singh TD, Lee SW et al (2014) Evaluation of therapeutic effects of natural killer (NK) cell-based immunotherapy in mice using in vivo apoptosis bioimaging with a caspase-3 sensor. FASEB J 28:2932\u20132941","journal-title":"FASEB J"},{"key":"1621_CR66","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1007\/s10495-013-0849-z","volume":"18","author":"Q Fu","year":"2013","unstructured":"Fu Q, Duan X, Yan S et al (2013) Bioluminescence imaging of caspase-3 activity in mouse liver. Apoptosis 18:998\u20131007","journal-title":"Apoptosis"},{"key":"1621_CR67","doi-asserted-by":"crossref","first-page":"e66248","DOI":"10.1371\/journal.pone.0066248","volume":"8","author":"S Galban","year":"2013","unstructured":"Galban S, Jeon YH, Bowman BM et al (2013) Imaging proteolytic activity in live cells and animal models. PLoS ONE 8:e66248","journal-title":"PLoS ONE"},{"key":"1621_CR68","doi-asserted-by":"crossref","first-page":"7595","DOI":"10.1002\/anie.200700538","volume":"46","author":"A Kanno","year":"2007","unstructured":"Kanno A, Yamanaka Y, Hirano H, Umezawa Y, Ozawa T (2007) Cyclic luciferase for real-time sensing of caspase-3 activities in living mammals. Angew Chem Int Ed Eng 46:7595\u20137599","journal-title":"Angew Chem Int Ed Eng"},{"key":"1621_CR69","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-1-60327-321-3_9","volume":"574","author":"A Kanno","year":"2009","unstructured":"Kanno A, Umezawa Y, Ozawa T (2009) Detection of apoptosis using cyclic luciferase in living mammals. Methods Mol Biol 574:105\u2013114","journal-title":"Methods Mol Biol"},{"key":"1621_CR70","doi-asserted-by":"crossref","first-page":"207","DOI":"10.7150\/thno.3806","volume":"2","author":"M Ozaki","year":"2012","unstructured":"Ozaki M, Haga S, Ozawa T (2012) In vivo monitoring of liver damage using caspase-3 probe. Theranostics 2:207\u2013214","journal-title":"Theranostics"},{"key":"1621_CR71","doi-asserted-by":"crossref","first-page":"190","DOI":"10.7150\/thno.5825","volume":"3","author":"G Niu","year":"2013","unstructured":"Niu G, Zhu L, Ho DN et al (2013) Longitudinal bioluminescence imaging of the dynamics of doxorubicin induced apoptosis. Theranostics 3:190\u2013200","journal-title":"Theranostics"},{"key":"1621_CR72","doi-asserted-by":"crossref","first-page":"22355","DOI":"10.18632\/oncotarget.7971","volume":"7","author":"Y Wang","year":"2016","unstructured":"Wang Y, Zhang B, Liu W et al (2016) Noninvasive bioluminescence imaging of the dynamics of sanguinarine induced apoptosis via activation of reactive oxygen species. Oncotarget 7:22355\u201322367","journal-title":"Oncotarget"},{"key":"1621_CR73","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.1039\/c2an35741k","volume":"137","author":"M Nazari","year":"2012","unstructured":"Nazari M, Emamzadeh R, Hosseinkhani S, Cevenini L, Michelini E, Roda A (2012) Renilla luciferase-labeled Annexin V: a new probe for detection of apoptotic cells. Analyst 137:5062\u20135070","journal-title":"Analyst"},{"key":"1621_CR74","doi-asserted-by":"crossref","first-page":"e2826","DOI":"10.1038\/cddis.2017.141","volume":"8","author":"T Head","year":"2017","unstructured":"Head T, Dau P, Duffort S et al (2017) An enhanced bioluminescence-based Annexin V probe for apoptosis detection in vitro and in vivo. Cell Death Dis 8:e2826\u2013e2826","journal-title":"Cell Death Dis"},{"key":"1621_CR75","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.ymthe.2004.10.016","volume":"11","author":"BA Tannous","year":"2005","unstructured":"Tannous BA, Kim D-E, Fernandez JL, Weissleder R, Breakefield XO (2005) Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol Ther 11:435\u2013443","journal-title":"Mol Ther"},{"key":"1621_CR76","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1021\/acschembio.7b00454","volume":"12","author":"S Gaur","year":"2017","unstructured":"Gaur S, Bhargava-Shah A, Hori S et al (2017) Engineering intracellularly retained Gaussia luciferase reporters for improved biosensing and molecular imaging applications. ACS Chem Bio 12:2345\u20132353","journal-title":"ACS Chem Bio"},{"key":"1621_CR77","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/340066a0","volume":"340","author":"M Eilers","year":"1989","unstructured":"Eilers M, Picard D, Yamamoto KR, Bishop JM (1989) Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells. Nature 340:66\u201368","journal-title":"Nature"},{"key":"1621_CR78","doi-asserted-by":"crossref","first-page":"5114","DOI":"10.1073\/pnas.88.12.5114","volume":"88","author":"G Superti-Furga","year":"1991","unstructured":"Superti-Furga G, Bergers G, Picard D, Busslinger M (1991) Hormone-dependent transcriptional regulation and cellular transformation by Fos-steroid receptor fusion proteins. P Natl Acad Sci USA 88:5114\u20135118","journal-title":"P Natl Acad Sci USA"},{"key":"1621_CR79","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1073\/pnas.90.9.4290","volume":"90","author":"DI Israel","year":"1993","unstructured":"Israel DI, Kaufman RJ (1993) Dexamethasone negatively regulates the activity of a chimeric dihydrofolate reductase\/glucocorticoid receptor protein. P Natl Acad Sci USA 90:4290\u20134294","journal-title":"P Natl Acad Sci USA"},{"key":"1621_CR80","doi-asserted-by":"crossref","first-page":"16551","DOI":"10.1073\/pnas.252644499","volume":"99","author":"B Laxman","year":"2002","unstructured":"Laxman B, Hall DE, Bhojani MS et al (2002) Noninvasive real-time imaging of apoptosis. Proc Natl Acad Sci USA 99:16551\u201316555","journal-title":"Proc Natl Acad Sci USA"},{"key":"1621_CR81","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1038\/jid.2010.55","volume":"130","author":"D Khanna","year":"2010","unstructured":"Khanna D, Hamilton CA, Bhojani MS et al (2010) A transgenic mouse for imaging caspase-dependent apoptosis within the skin. J Investig Dermatol 130:1797\u20131806","journal-title":"J Investig Dermatol"},{"key":"1621_CR82","first-page":"2539","volume":"35","author":"M Yang","year":"2015","unstructured":"Yang M, Jiang P, Hoffman RM (2015) Early reporting of apoptosis by real-time imaging of cancer cells labeled with green fluorescent protein in the nucleus and red fluorescent protein in the cytoplasm. Anticancer Res 35:2539\u20132543","journal-title":"Anticancer Res"},{"key":"1621_CR83","doi-asserted-by":"crossref","first-page":"6865","DOI":"10.1038\/sj.onc.1206748","volume":"22","author":"K Shah","year":"2003","unstructured":"Shah K, Tang Y, Breakefield X, Weissleder R (2003) Real-time imaging of TRAIL-induced apoptosis of glioma tumors in vivo. Oncogene 22:6865\u20136872","journal-title":"Oncogene"},{"key":"1621_CR84","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1038\/onc.2012.304","volume":"32","author":"T Bagci-Onder","year":"2013","unstructured":"Bagci-Onder T, Agarwal A, Flusberg D, Wanningen S, Sorger P, Shah K (2013) Real-time imaging of the dynamics of death receptors and therapeutics that overcome TRAIL resistance in tumors. Oncogene 32:2818\u20132827","journal-title":"Oncogene"},{"key":"1621_CR85","unstructured":"Singh TD, Lee HW, Lee S-W, et al. (2014) Noninvasive imaging of apoptosis induced by adenovirus-mediated cancer gene therapy using a caspase-3 biosensor in living subjects. Mol Imaging 13."},{"key":"1621_CR86","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/mt.2011.17","volume":"19","author":"JM Niers","year":"2011","unstructured":"Niers JM, Kerami M, Pike L, Lewandrowski G, Tannous BA (2011) Multimodal in vivo imaging and blood monitoring of intrinsic and extrinsic apoptosis. Mol Ther 19:1090\u20131096","journal-title":"Mol Ther"},{"key":"1621_CR87","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1038\/mtna.2013.25","volume":"2","author":"CA Maguire","year":"2013","unstructured":"Maguire CA, Bovenberg MS, Crommentuijn MH et al (2013) Triple bioluminescence imaging for in vivo monitoring of cellular processes. Mol Ther-Nucl Acids 2:e99","journal-title":"Mol Ther-Nucl Acids"},{"key":"1621_CR88","doi-asserted-by":"crossref","first-page":"5801","DOI":"10.1158\/1078-0432.CCR-07-5244","volume":"14","author":"P Ray","year":"2008","unstructured":"Ray P, De A, Patel M, Gambhir SS (2008) Monitoring caspase-3 activation with a multimodality imaging sensor in living subjects. Clin Cancer Res 14:5801\u20135809","journal-title":"Clin Cancer Res"},{"key":"1621_CR89","doi-asserted-by":"crossref","first-page":"302","DOI":"10.7150\/thno\/v01p0302","volume":"1","author":"F Zhang","year":"2011","unstructured":"Zhang F, Zhu L, Liu G et al (2011) Multimodality imaging of tumor response to doxil. Theranostics 1:302\u2013309","journal-title":"Theranostics"},{"key":"1621_CR90","doi-asserted-by":"crossref","first-page":"413","DOI":"10.7150\/thno.3940","volume":"2","author":"G Niu","year":"2012","unstructured":"Niu G, Chen X (2012) Molecular imaging with activatable reporter systems. Theranostics 2:413","journal-title":"Theranostics"},{"key":"1621_CR91","doi-asserted-by":"crossref","first-page":"100144","DOI":"10.1016\/j.pacs.2019.100144","volume":"16","author":"ABE Attia","year":"2019","unstructured":"Attia ABE, Balasundaram G, Moothanchery M et al (2019) A review of clinical photoacoustic imaging: current and future trends. Photoacoustics 16:100144","journal-title":"Photoacoustics"},{"key":"1621_CR92","doi-asserted-by":"crossref","first-page":"116026","DOI":"10.1117\/1.3650240","volume":"16","author":"Q Yang","year":"2011","unstructured":"Yang Q, Cui H, Cai S, Yang X, Forrest ML (2011) In vivo photoacoustic imaging of chemotherapy-induced apoptosis in squamous cell carcinoma using a near-infrared caspase-9 probe. J Biomed Opt 16:116026","journal-title":"J Biomed Opt"},{"key":"1621_CR93","doi-asserted-by":"crossref","first-page":"4886","DOI":"10.1002\/anie.201813748","volume":"58","author":"Y Wang","year":"2019","unstructured":"Wang Y, Hu X, Weng J et al (2019) A photoacoustic probe for the imaging of tumor apoptosis by caspase-mediated macrocyclization and self-assembly. Angew Chem Int Ed Engl 58:4886\u20134890","journal-title":"Angew Chem Int Ed Engl"}],"container-title":["Apoptosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10495-020-01621-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10495-020-01621-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10495-020-01621-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T23:35:06Z","timestamp":1625355306000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10495-020-01621-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,4]]},"references-count":93,"journal-issue":{"issue":"7-8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["1621"],"URL":"https:\/\/doi.org\/10.1007\/s10495-020-01621-5","relation":{},"ISSN":["1360-8185","1573-675X"],"issn-type":[{"value":"1360-8185","type":"print"},{"value":"1573-675X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,4]]},"assertion":[{"value":"4 July 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"No potential conflicts of interest were disclosed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}