18 1 2006 2 Chinese Bulletin of Life Sciences Vol. 18, No. 1 Feb., 2006 1004-0374(2006)01-0025-06 1 100005 2 100084 Q-331; R319 A Current developments in animal in vivo optical imaging technologies with bioluminescence and fluorescence ZHANG Yi 1, HAN Yu 2, ZHAO Chun-Lin 2 * (1 Institute of Basic Medical Sciences, CAMS and PUMC, Beijing 100005, China; 2 Longmed, Inc., Beijing 100084, China) Abstract: Bioluminescence and fluorescence have been proved to be a versatile tool for in vivo imaging. Reporters that confer optical signals on a given biological process have been used widely in cell biology and more recently to interrogate biological process in animal models of human biology and disease. The theories, technologies, and the applications of these technologies will be compared and reviewed, especially the advantages and disadvantages between bioluminescence and fluorescence in vivo imaging. We also discussed the different technologies and applications about multi-spectral imaging and time-domain optical imaging, and reviewed the trend for future developments of these technologies. Key words: optical in vivo imaging; animal imaging; bioluminescence; luciferase; fluorescence; multi-spectral imaging; time domain optical imaging (optical in vivo imaging) (bioluminescence) (fluorescence) (luciferase) DNA (GFP RFP Cyt dyes ) [1] 2005-10-18 (1978 ) (1977 ) (1968 ) *
26 (ultrasound) (computed tomography, CT) (magnetic resonance imaging, MRI) (positron-emission tomography, PET) (single-photon-emission computed tomography, SPECT) [2~4] 1 1995 Contag Lux [1] 1997 Fluc (luciferase) [2, 4] Lux [1] Fluc DNA ATP ( ) (luciferin) (Xenogen Corp.) IVIS ( 1) CCD [5] (350~600nm) (>900nm) (600~900nm) [5] IVIS 100 [6] ( 2) 2 1 2 [7]
27 (GFP) (DsRed) [8] CRI GE-ART (time domain, TD) [2,4] Xenogen IVIS 400~950 nm (blue-shifted background filters) [5] CRI Maestro (multi-spectral imaging) 10nm [9] [10] (time domain optical imaging, TDOI) GE ( 3) 1mm [2] 1mm [2] 3 [10] 10 6 3 (Vera et al, UCSD, GE Optix)
28 1 FACS 10 2, CCD 10 6 10 2 [6,11~12] [4,12~16] [8~9] ( 1) [6,17~18] 4 ATP CT, PET [3] CT CT [19~21] [4,22] FDA 5 DNA, [23~24] 100 [24] [14] FDA [4,22]
29 [18] [6] Lentivirus [18,25] [29] T [6,18] DNA sirna [3,10,26] AAV2 AAV5 Sindbis CMV HPV [10, 27] [28] DNA DNA [5] McCaffrey [26] sirna shrna sirna [29] Zhang [21] (inos-luc) NO (inos) VGEF2 Luc [30] GFAP Luc (Alzheimer Disease) [29] ( p450) Luc [19] [4] Paulmurugan [31] II (IGF-II) 6(IGFBP-6) GFP Renilla [13] 6 CT MRI PET [3] [4] [1] Contag P R, Olomu I N, Stenvenson D K, et al. Bioluminescent indicators in living mammals. Nat Med, 1998, 4(2): 245~247 [2] Ntziachristos V, Ripoll J, Wang L V, et al. Looking and listenting to light: the evolution of whole-body photonic imaging. Nat Biotechnol, 2005, 23(3): 313~320 [3] Iyer M, Berenji M, Templeton N S, et al. Noninvasive imaging of cationic lipid-mediated delivery of optical and PET reporter genes in living mice. Mol Ther, 2002, 6(4): 555~562 [4] Maggi A, Ciana P. Reporter mice and drug discovery and development. Nat Rev Drug Discov, 2005, 4(3): 249~255 [5] Rice B W, Cable M D, Nelson M B. In vivo imaging of lightemitting probes. J Biomed Opt, 2001, 6(4): 432~440 [6] Edinger M, Cao Y A, Verneris M R, et al. Revealing lym-
30 phoma growth and the efficacy of immune cell therapies using in vivo bioluminescence imaging. Blood, 2003, 101(2):640~648 [7] Minn A J, Kang Y, Serganova I, et al. Distinct organ-specific metastalic potential of individual breast cancer cells and primary tumors. J Clin Invest, 2005, 115: 44~55 [8] Chen X Y, Conti P S, Moats R A. In vivo near-infrared fluorescence imaging of integrin α v β 3 in brain tumor xenografts. Cancer Res, 2004, 64: 8009~8014 [9] Gao X H, Cui Y Y, Levenson R M, et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol, 2004, 22: 969~976 [10] Tseng J C, Levin B, Hurtado A, et al. Systemic tumor targeting and killing by sindbis viral vectors. Nat Biotechnol, 2004, 22: 70~77 [11] Troy T, Jekic-McMullen D, Sambucetti L, et al. Quantitative comparison of the sensitivity of detection of fluorescent and bioluminscent reporters in animal models. Mol Imaging, 2004, 3(1): 9~23 [12] Minn A J, Gupta G P, Siegel P M, et al, Genes that mediate breast cancer metastasis to lung. Nature, 2005, 436: 518~524 [13] Shachaf C M, Kopelman A M, Arvanitis C, et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature, 2004, 431: 1112~1117 [14] Walensky L D, Kung A L, Escher I, et al. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science, 2004, 305: 1466~1470 [15] Morizono K, Xie Y M, Ringpis G E, et al. Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection. Nat Med, 2005, 11: 346~352 [16] Gross S, Piwnica-Worms D. Real-time imaging of ligandinduced IKK activation in intact cells and in living mice. Nat Methods, 2005, 2: 607~614 [17] Zhang G J, Safran M, Wei W Y, et al. Bioluminescent imaging of Cdk2 inhibition in vivo. Nat Med, 2004, 10: 643~648 [18] Wang X L, Rosol M, Ge S D, et al. Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging. Blood, 2003, 102: 3478~3482 [19] Zhang W S, Purchio A F, Chen K, et al. A transgenic mouse model with a luciferase reporter for studying in vivo transcriptional regulation of the human CYP3A4 gene. Drug Metab Dispos, 2003, 31(8): 1054~1064 [20] Kim J H, Kim B, Cai L, et al. Transcriptional regulation of a metastasis suppressor gene by Tip60 and β-catenin complexes. Nature, 2005, 434: 921~926 [21] Zhang N, Weber A, Li B, et al. An inducible nitric oxide synthase-luciferase reporter system for in vivo testing of anti-inflammatory compounds in transgenic mice. J Immunol, 2003, 170: 6307~6319 [22] Mendel D B, Laird A D, Xin X H, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res, 2003, 9(1): 327~337 [23] Contag P R. Whole-animal cellular and molecular imaging to accelerate drug development. Drug Discov Today, 2002, 7 (10): 555~562 [24] Jenkins D E, Oei Y, Hornig Y S, et al. Bioluminescent imaging (BLI) to improve and refine traditional murine models of tumor growth and metastasis. Clin Exp Metastasis, 2003, 20 (8):733~744 [25] Cao Y A, Wagers A J, Beilhack A, et al. Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc Natl Acad Sci USA, 2004, 101(1): 221~226 [26] McCaffrey A P, Meuse L, Pham T T, et al. RNA interference in adult mice. Nature, 2002, 418: 38~39 [27] Sato M, Johnson M, Zhang L Q, et al. Optimization of adenoviral vectors to direct highly amplified prostate-specific expression for imaging and gene therapy. Mol Ther, 2003, 8(5): 726~737 [28] Luker G D, Prior J L, Song J L, et al. Bioluminescence imaging reveals systemic dissemination of herpes simplex virus type 1 in the absence of interferon receptors. J VIirol, 2003, 77(20): 11082~11093 [29] Zhu L Y, Ramboz S, Hewitt D, et al. Non-invasive imaging of GFAP expression after neuronal damage in mice. Neurosci Lett, 2004, 367: 210~212 [30] Zhang N, Fang Z X, Contag P R, et al. Tracking angiogenesis induced by skin wounding and contact hypersensitivity using a Vegfr2-luciferase transgenic mouse. Blood, 2004, 103: 617~626 [31] Paulmurugan R, Gambhir S S. Monitoring protein-protein interactions using split synthetic renilla luciferase proteinfragment-assisted complementation. Anal Chem, 2003, 75: 1584~1589