Molecular-genetic imaging

Molecular Imaging in Oncology

Volumn , Issue , 2008, Pages 443-467

  Waerzeggers, Yannic ^a   Winkeler, Alexandra ^a   Jacobs, Andreas H ^a  

^a UNIVERSITY OF COLOGNE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84986561421     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (218)

1. Blasberg RG, Gelovani-Tjuvajev J. In vivo molecular-genetic imaging. J Cell Biochem Suppl 2002; 39:172-183.
2. Weissleder R, Mahmood U. Molecular imaging. Radiology 2001; 219:316-333.
3. Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003; 17:545-580.
4. Townsend DW, Beyer T. A combined PET/CT scanner: the path to true image fusion. Br J Radiol 2002; 75 Spec No:S24-S30.
5. Beyer T, Townsend DW. Putting 'clear' into nuclear medicine: a decade of PET/CT development. Eur J Nucl Med Mol Imaging 2006; 33:857-861.
6. Pichler BJ, Judenhofer MS, Catana C, et al. Performance test of an LSO-APD detector in a 7-T MRI scanner for simultaneous PET/MRI. J Nucl Med 2006; 47:639-647.
7. Raylman RR, Majewski S, Lemieux SK, et al. Simultaneous MRI and PET imaging of a rat brain. Phys Med Biol 2006; 51:6371-6379.
8. Cizek J, Herholz K, Vollmar S, et al. Fast and robust registration of PET and MR images of human brain. Neuroimage 2004; 22:434-442.
9. Ray P, De A, Min JJ, et al. Imaging tri-fusion multi-modality reporter gene expression in living subjects. Cancer Res 2004; 64:1323-1330.
10. Phelps ME. PET: the merging of biology and imaging into molecular imaging. J Nucl Med 2000; 41:661-681.
11. Acton PD, Kung HF. Small animal imaging with highresolution single photon emission tomography. Nucl Med Biol 2003; 30:889-895.
12. Shah K, Jacobs A, Breakefield XO, et al. Molecular imaging of gene therapy for cancer. Gene Ther 2004; 11:1175-1187.
13. Contag CH, Bachmann MH. Advances in in vivo bio-luminescence imaging of gene expression. Annu Rev Biomed Eng 2002; 4:235-260.
14. Blasberg RG, Tjuvajev JG. Molecular-genetic imaging: current and future perspectives. J Clin Invest 2003; 111:1620-1629.
15. Tavitian B. In vivo imaging with oligonucleotides for diagnosis and drug development. Gut 2003; 52(suppl 4): iv40-iv47.
16. Perez JM, Josephson L, Weissleder R. Use of magnetic nanoparticles as nanosensors to probe for molecular interactions. Chembiochem 2004; 5:261-264.
17. Perez JM, Josephson L, O'Loughlin T, et al. Magnetic relaxation switches capable of sensing molecular interactions. Nat Biotechnol 2002; 20:816-820.
18. Grimm J, Perez JM, Josephson L, et al. Novel nanosensors for rapid analysis of telomerase activity. Cancer Res 2004; 64:639-643.
19. Pickles MD, Lowry M, Manton DJ, et al. Role of dynamic contrast enhanced MRI in monitoring early response of locally advanced breast cancer to neoadjuvant chemotherapy. Breast Cancer Res Treat 2005; 91:1-10.
20. Turetschek K, Preda A, Floyd E, et al. MRI monitoring of tumor response following angiogenesis inhibition in an experimental human breast cancer model. Eur J Nucl Med Mol Imaging 2003; 30:448-455.
21. Checkley D, Tessier JJ, Kendrew J, et al. Use of dynamic contrast-enhanced MRI to evaluate acute treatment with ZD6474, a VEGF signalling inhibitor, in PC-3 prostate tumours. Br J Cancer 2003; 89:1889-1895.
22. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347:472-480.
23. Van den Abbeele AD, Badawi RD. Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs). Eur J Cancer 2002; 38(suppl 5):S60-S65.
24. Pio BS, Park CK, Pietras R, et al. Usefulness of 3'-[F-18] fluoro-3'-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol 2006; 8:36-12.
25. Bogdanov A Jr., Weissleder R. The development of in vivo imaging systems to study gene expression. Trends Biotechnol 1998; 16:5-10.
26. Doubrovin M, Serganova I, Mayer-Kuckuk P, et al. Multi-modality in vivo molecular-genetic imaging. Bioconjug Chem 2004; 15:1376-1388.
27. Jacobs A, Dubrovin M, Hewett J, et al. Functional coex-pression of HSV-1 thymidine kinase and green fluorescent protein: implications for noninvasive imaging of transgene expression. Neoplasia 1999; 1:154-161.
28. Ponomarev V, Doubrovin M, Serganova I, et al. Cyto-plasmically retargeted HSV1-tk/GFP reporter gene mutants for optimization of noninvasive molecular-genetic imaging. Neoplasia 2003; 5:245-254.
29. Ray P, Wu AM, Gambhir SS. Optical bioluminescence and positron emission tomography imaging of a novel fusion reporter gene in tumor xenografts of living mice. Cancer Res 2003; 63:1160-1165.
30. Wang Y, Yu YA, Shabahang S, et al. Renilla luciferase-Aequorea GFP (Ruc-GFP) fusion protein, a novel dual reporter for real-time imaging of gene expression in cell cultures and in live animals. Mol Genet Genomics 2002; 268:160-168.
31. Kummer C, Winkeler A, Dittmar C, et al. Multitracer positron emission tomographic imaging of exogenous gene expression mediated by a universal herpes simplex virus 1 amplicon vector. Mol Imaging 2007; 6:181-192.
32. Ray P, Tsien R, Gambhir SS. Construction and validation of improved triple fusion reporter gene vectors for molecular imaging of living subjects. Cancer Res 2007; 67:3085-3093.
33. Tjuvajev JG, Joshi A, Callegari J, et al. A general approach to the non-invasive imaging of transgenes using cis-linked herpes simplex virus thymidine kinase. Neoplasia 1999; 1:315-320.
34. Jacobs AH, Winkeler A, Hartung M, et al. Improved herpes simplex virus type 1 amplicon vectors for proportional coexpression of positron emission tomography marker and therapeutic genes. Hum Gene Ther 2003; 14:277-297.
35. Serganova I, Blasberg R. Reporter gene imaging: potential impact on therapy. Nucl Med Biol 2005; 32:763-780.
36. Serganova I, Doubrovin M, Vider J, 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 2004; 64:6101-6108.
37. Gambhir SS, Barrio JR, Herschman HR, et al. Assays for noninvasive imaging of reporter gene expression. Nucl Med Biol 1999; 26:481-490.
38. Gambhir SS, Herschman HR, Cherry SR, et al. Imaging transgene expression with radionuclide imaging technologies. Neoplasia 2000; 2:118-138.
39. Herschman HR. PET reporter genes for noninvasive imaging of gene therapy, cell tracking and transgenic analysis. Crit Rev Oncol Hematol 2004; 51:191-204.
40. Serganova I, Ponomarev V, Blasberg R. Human reporter genes: potential use in clinical studies. Nucl Med Biol 2007; 34:791-807.
41. Saito Y, Price RW, Rottenberg DA, et al. Quantitative autoradiographic mapping of herpes simplex virus encephalitis with a radiolabeled antiviral drug. Science 1982; 217:1151-1153.
42. Tjuvajev JG, Stockhammer G, Desai R, et al. Imaging the expression of transfected genes in vivo. Cancer Res 1995; 55:6126-6132.
43. Tjuvajev JG, Finn R, Watanabe K, et al. Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy. Cancer Res 1996; 56:4087-4095.
44. Gambhir SS, Bauer E, Black ME, et al. A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography. Proc Natl Acad Sci USA 2000; 97:2785-2790.
45. Tjuvajev JG, Doubrovin M, Akhurst T, et al. Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression. J Nucl Med 2002; 43:1072-1083.
46. Min JJ, Iyer M, Gambhir SS. Comparison of [18F]FHBG and [14C]FIAU for imaging of HSVl-tk reporter gene expression: adenoviral infection vs stable transfection. Eur J Nucl Med Mol Imaging 2003; 30:1547-1560.
47. Hackman T, Doubrovin M, Balatoni J, et al. Imaging expression of cytosine deaminase-herpes virus thymidine kinase fusion gene (CD/TK) expression with [124I]FIAU and PET. Mol Imaging 2002; 1:36-12.
48. Stegman LD, Rehemtulla A, Beattie B, et al. Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy. Proc Natl Acad Sci USA 1999; 96:9821-9826.
49. Doubrovin M, Ponomarev V, Serganova I, et al. Development of a new reporter gene system-dsRed/xanthine phosphoribosyltransferase-xanthine for molecular imaging of processes behind the intact blood-brain barrier. Mol Imaging 2003; 2:93-112.
50. Conti PS, Alauddin MM, Fissekis JR, et al. Synthesis of 2'-fluoro-5-[11C]-methyl-1-beta-D-arabinofuranosyluracil ([11C]-FMAU): a potential nucleoside analog for in vivo study of cellular proliferation with PET. Nucl Med Biol 1995; 22:783-789.
51. Mangner TJ, Klecker RW, Anderson L, et al. Synthesis of 2'-deoxy-2'-[18F]fluoro-beta-D-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F] FIAU, as potential PET agents for imaging cellular proliferation. Synthesis of [18F]labelled FAU, FMAU, FBAU, FIAU. Nucl Med Biol 2003; 30:215-224.
52. Ponomarev V, Doubrovin M, Shavrin A, et al. A human-derived reporter gene for noninvasive imaging in humans: mitochondrial thymidine kinase type 2. J Nucl Med 2007; 48:819-826.
53. Neve KA, Cox BA, Henningsen RA, et al. Pivotal role for aspartate-80 in the regulation of dopamine D2 receptor affinity for drugs and inhibition of adenylyl cyclase. Mol Pharmacol 1991; 39:733-739.
54. Liang Q, Satyamurthy N, Barrio JR, et al. Noninvasive, quantitative imaging in living animals of a mutant dopa-mine D2 receptor reporter gene in which ligand binding is uncoupled from signal transduction. Gene Ther 2001; 8:1490-1498.
55. MacLaren DC, Gambhir SS, Satyamurthy N, et al. Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals. Gene Ther 1999; 6:785-791.
56. Ogawa O, Umegaki H, Ishiwata K, et al. In vivo imaging of adenovirus-mediated over-expression of dopamine D2 receptors in rat striatum by positron emission tomography. Neuroreport 2000; 11:743-748.
57. Umegaki H, Ishiwata K, Ogawa O, et al. In vivo assessment of adenoviral vector-mediated gene expression of dopamine D(2) receptors in the rat striatum by positron emission tomography. Synapse 2002; 43:195-200.
58. Sun X, Annala AJ, Yaghoubi SS, et al. Quantitative imaging of gene induction in living animals. Gene Ther 2001; 8:1572-1579.
59. Groot-Wassink T, Aboagye EO, Wang Y, et al. Non-invasive imaging of the transcriptional activities of human telomerase promoter fragments in mice. Cancer Res 2004; 64:4906-4911.
60. Zinn KR, Chaudhuri TR, Krasnykh VN, et al. Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after gene transfer with a bicistronic adenovirus in mice. Radiology 2002; 223:417-425.
61. Zinn KR, Chaudhuri TR. The type 2 human somatostatin receptor as a platform for reporter gene imaging. Eur J Nucl Med Mol Imaging 2002; 29:388-399.
62. Boland A, Ricard M, Opolon P, et al. Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy. Cancer Res 2000; 60:3484-3492.
63. Spitzweg C, Zhang S, Bergert ER, et al. Prostate-specific antigen (PSA) promoter-driven androgen-inducible expression of sodium iodide symporter in prostate cancer cell lines. Cancer Res 1999; 59:2136-2141.
64. Spitzweg C, Dietz AB, O'Connor MK, et al. In vivo sodium iodide symporter gene therapy of prostate cancer. Gene Ther 2001; 8:1524-1531.
65. Sieger S, Jiang S, Schonsiegel F, et al. Tumour-specific activation of the sodium/iodide symporter gene under control of the glucose transporter gene 1 promoter (GTI-1.3). Eur J Nucl Med Mol Imaging 2003; 30:748-756.
66. Huang M, Batra RK, Kogai T, et al. Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non-small cell lung cancer. Cancer Gene Ther 2001; 8:612-618.
67. Axelrod J, Kopin IJ. The uptake, storage, release and metabolism of noradrenaline in sympathetic nerves. Prog Brain Res 1969; 31:21-32.
68. Moroz MA, Serganova I, Zanzonico P, et al. Imaging hNET reporter gene expression with 124I-MIBG. J Nucl Med 2007; 48:827-836.
69. Bonini C, Ferrari G, Verzeletti S, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997; 276:1719-1724.
70. Verzeletti S, Bonini C, Marktel S, et al. Herpes simplex virus thymidine kinase gene transfer for controlled graft-versus-host disease and graft-versus-leukemia: clinical follow-up and improved new vectors. Hum Gene Ther 1998; 9:2243-2251.
71. Jacobs A, Voges J, Reszka R, et al. Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 2001; 358:727-729.
72. Penuelas I, Mazzolini G, Boan JF, et al. Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology 2005; 128:1787-1795.
73. Ntziachristos V, Bremer C, Weissleder R. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol 2003; 13:195-208.
74. Shah K, Tung CH, Chang CH, et al. In vivo imaging of HIV protease activity in amplicon vector-transduced gliomas. Cancer Res 2004; 64:273-278.
75. Bhaumik S, Lewis XZ, Gambhir SS. Optical imaging of Renilla luciferase, synthetic Renilla luciferase, and firefly luciferase reporter gene expression in living mice. J Biomed Opt 2004; 9:578-586.
76. Shah K, Tang Y, Breakefield X, et al. Real-time imaging of TRAIL-induced apoptosis of glioma tumors in vivo. Oncogene 2003; 22:6865-6872.
77. Shah K, Bureau E, Kim DE, et al. Glioma therapy and real-time imaging of neural precursor cell migration and tumor regression. Ann Neurol 2005; 57:34-11.
78. Kolb VA, Makeyev EV, Spirin AS. Co-translational folding of an eukaryotic multidomain protein in a prokaryotic translation system. J Biol Chem 2000; 275:16597-16601.
79. Thompson JF, Hayes LS, Lloyd DB. Modulation of firefly luciferase stability and impact on studies of gene regulation. Gene 1991; 103:171-177.
80. Day RN, Kawecki M, Berry D. Dual-function reporter protein for analysis of gene expression in living cells. Biotechniques 1998; 25:848-850, 852-854, 856.
81. Uhrbom L, Nerio E, Holland EC. Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nat Med 2004; 10:1257-1260.
82. Vooijs M, Jonkers J, Lyons S, et al. Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer Res 2002; 62:1862-1867.
83. Rehemtulla A, Hall DE, Stegman LD, et al. Molecular imaging of gene expression and efficacy following adenoviral-mediated brain tumor gene therapy. Mol Imaging 2002; 1:43-55.
84. Soling A, Theiss C, Jungmichel S, et al. A dual function fusion protein of Herpes simplex virus type 1 thymidine kinase and firefly luciferase for noninvasive in vivo imaging of gene therapy in malignant glioma. Genet Vaccines Ther 2004; 2:7.
85. Rehemtulla A, Stegman LD, Cardozo SJ, et al. Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia 2000; 2:491-495.
86. Tang Y, Shah K, Messerli SM, et al. In vivo tracking of neural progenitor cell migration to glioblastomas. Hum Gene Ther 2003; 14:1247-1254.
87. Michalet X, Pinaud FF, Bentolila LA, et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 2005; 307:538-544.
88. Wu X, Liu H, Liu J, et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol 2003; 21:41-46.
89. Gao X, Cui Y, Levenson RM, et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 2004; 22:969-976.
90. Akerman ME, Chan WC, Laakkonen P, et al. Nanocrystal targeting in vivo. Proc Natl Acad Sci U S A 2002; 99:12617-12621.
91. Gao X, Chung LW, Nie S. Quantum dots for in vivo molecular and cellular imaging. Methods Mol Biol 2007; 374:135-145.
92. Gilad AA, Winnard PT Jr., van Zijl PC, et al. Developing MR reporter genes: promises and pitfalls. NMR Biomed 2007; 20:275-290.
93. Blackstock AW, Lightfoot H, Case LD, et al. Tumor uptake and elimination of 2',2'-difluoro-2'-deoxycytidine (gemcitabine) after deoxycytidine kinase gene transfer: correlation with in vivo tumor response. Clin Cancer Res 2001; 7:3263-3268.
94. Auricchio A, Zhou R, Wilson JM, et al. In vivo detection of gene expression in liver by 31P nuclear magnetic resonance spectroscopy employing creatine kinase as a marker gene. Proc Natl Acad Sci U S A 2001; 98:5205-5210.
95. Li Z, Qiao H, Lebherz C, et al. Creatine kinase, a magnetic resonance-detectable marker gene for quantification of liver-directed gene transfer. Hum Gene Ther 2005; 16:1429-1438.
96. Walter G, Barton ER, Sweeney HL. Noninvasive measurement of gene expression in skeletal muscle. Proc Natl Acad Sci U S A 2000; 97:5151-5155.
97. Weissleder R, Moore A, Mahmood U, et al. In vivo magnetic resonance imaging of transgene expression. Nat Med 2000; 6:351-355.
98. Moore A, Josephson L, Bhorade RM, et al. Human trans-ferrin receptor gene as a marker gene for MR imaging. Radiology 2001; 221:244-250.
99. Funovics MA, Kapeller B, Hoeller C, et al. MR imaging of the her2/neu and 9.2.27 tumor antigens using immunospe-cific contrast agents. Magn Reson Imaging 2004; 22: 843-850.
100. McAteer MA, Sibson NR, von Zur Muhlen C, et al. In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide. Nat Med 2007; 13:1253-1258.
101. Sipkins DA, Gijbels K, Tropper FD, et al. ICAM-1 expression in autoimmune encephalitis visualized using magnetic resonance imaging. J Neuroimmunol 2000; 104:1-9.
102. Louie AY, Huber MM, Ahrens ET, et al. In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 2000; 18:321-325.
103. Cui W, Otten P, Li Y, et al. Novel NMR approach to assessing gene transfection: 4-fluoro-2-nitrophenyl-beta-D-galactopyranoside as a prototype reporter molecule for beta-galactosidase. Magn Reson Med 2004; 51:616-620.
104. Kodibagkar VD, Yu J, Liu L, et al. Imaging beta-galactosidase activity using 19F chemical shift imaging of LacZ gene-reporter molecule 2-fluoro-4-nitrophenol-beta-D-galactopyranoside. Magn Reson Imaging 2006; 24:959-962.
105. Cui W LL, Adam A, Yu J, et al. Detection of beta- galactosidase activity in a human tumor xenograft by 1H MRI in vivo using S-Gal. Proc Int Soc Magn Reson Med 2005; 13:2593.
106. Koretsky A LY-J, Schorle H, Jaenisch R. Genetic control of MRI contrast by expression of the transferrin receptor. Proc Int Soc Magn Reson Med 1996; 4:69.
107. Weissleder R, Simonova M, Bogdanova A, et al. MR imaging and scintigraphy of gene expression through melanin induction. Radiology 1997; 204:425-429.
108. Alfke H, Stoppler H, Nocken F, et al. In vitro MR imaging of regulated gene expression. Radiology 2003; 228:488-192.
109. Cohen B, Dafni H, Meir G, et al. Ferritin as an endogenous MRI reporter for noninvasive imaging of gene expression in C6 glioma tumors. Neoplasia 2005; 7:109-117.
110. Genove G, DeMarco U, Xu H, et al. A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 2005; 11:450-154.
111. Deans AE, Wadghiri YZ, Bernas LM, et al. Cellular MRI contrast via coexpression of transferrin receptor and ferritin. Magn Reson Med 2006; 56:51-59.
112. Hynes NE, Kennedy N, Rahmsdorf U, et al. Hormone-responsive expression of an endogenous proviral gene of mouse mammary tumor virus after molecular cloning and gene transfer into cultured cells. Proc Natl Acad Sci USA 1981; 78:2038-2042.
113. Mayo KE, Warren R, Palmiter RD. The mouse metal-lothionein-I gene is transcriptionally regulated by cadmium following transfection into human or mouse cells. Cell 1982; 29:99-108.
114. Wurm FM, Gwinn KA, Kingston RE. Inducible overproduction of the mouse c-myc protein in mammalian cells. Proc Natl Acad Sci U S A 1986; 83:5414-5418.
115. Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A 1992; 89:5547-5551.
116. Christopherson KS, Mark MR, Bajaj V, et al. Ecdysteroid-dependent regulation of genes in mammalian cells by a Drosophila ecdysone receptor and chimeric transactiva-tors. Proc Natl Acad Sci U S A 1992; 89:6314-6318.
117. No D, Yao TP, Evans RM. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci U S A 1996; 93:3346-3351.
118. Wang Y, O'Malley BW Jr., Tsai SY, O'Malley BW. A regulatory system for use in gene transfer. Proc Natl Acad Sci U S A 1994; 91:8180-8184.
119. Delort JP, Capecchi MR. TAXI/UAS: a molecular switch to control expression of genes in vivo. Hum Gene Ther 1996; 7:809-820.
120. Yu YA, Szalay AA. A Renilla luciferase-Aequorea GFP (ruc-gfp) fusion gene construct permits real-time detection of promoter activation by exogenously administered mife-pristone in vivo. Mol Genet Genomics 2002; 268:169-178.
121. Winkeler A, Sena-Esteves M, Paulis LE, et al. Switching on the lights for gene therapy. PLoS ONE 2007; 2:e528.
122. Iyer M, Wu L, Carey M, et al. Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters. Proc Natl Acad Sci USA 2001; 98:14595-14600.
123. Qiao J, Doubrovin M, Sauter BV, et al. Tumor-specific transcriptional targeting of suicide gene therapy. Gene Ther 2002; 9:168-175.
124. Wang W, El-Deiry WS. Bioluminescent molecular imaging of endogenous and exogenous p53-mediated transcription in vitro and in vivo using an HCT116 human colon carcinoma xenograft model. Cancer Biol Ther 2003; 2:196-202.
125. Doubrovin M, Ponomarev V, Beresten T, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci U S A 2001; 98:9300-9305.
126. Ponomarev V, Doubrovin M, Lyddane C, et al. Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. Neoplasia 2001; 3:480-488.
127. Gross S, Piwnica-Worms D. Real-time imaging of ligand-induced IKK activation in intact cells and in living mice. Nat Methods 2005; 2:607-614.
128. Ting AY, Kain KH, Klemke RL, et al. Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells. Proc Natl Acad Sci U S A 2001; 98:15003-15008.
129. Zhang J, Ma Y, Taylor SS, et al. Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering. Proc Natl Acad Sci U S A 2001; 98:14997-15002.
130. Zhang GJ, Safran M, Wei W, et al. Bioluminescent imaging of Cdk2 inhibition in vivo. Nat Med 2004; 10:643-648.
131. Zhang L, Lee KC, Bhojani MS, et al. Molecular imaging of Akt kinase activity. Nat Med 2007; 13:1114-1119.
132. Carlsen H, Moskaug JO, Fromm SH, et al. In vivo imaging of NF-kappa B activity. J Immunol 2002; 168:1441-1446.
133. Magness ST, Jijon H, Van Houten Fisher N, et al. In vivo pattern of lipopolysaccharide and anti-CD3-induced NF-kappa B activation using a novel gene-targeted enhanced GFP reporter gene mouse. J Immunol 2004; 173:1561-1570.
134. Zhang W, Purchio AF, 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; 31:1054-1064.
135. Lin AH, Luo J, Mondshein LH, et al. Global analysis of Smad2/3-dependent TGF-beta signaling in living mice reveals prominent tissue-specific responses to injury. J Immunol 2005; 175:547-554.
136. Zhang N, Ahsan MH, Purchio AF, et al. Serum amyloid A-luciferase transgenic mice: response to sepsis, acute arthritis, and contact hypersensitivity and the effects of proteasome inhibition. J Immunol 2005; 174:8125-8134.
137. Ohtani N, Imamura Y, Yamakoshi K, et al. Visualizing the dynamics of p21(Waf1/Cip1) cyclin-dependent kinase inhibitor expression in living animals. Proc Natl Acad Sci U S A 2007; 104:15034-15039.
138. Momota H, Holland EC. Bioluminescence technology for imaging cell proliferation. Curr Opin Biotechnol 2005; 16:681-686.
139. Green LA, Yap CS, Nguyen K, et al. Indirect monitoring of endogenous gene expression by positron emission tomography (PET) imaging of reporter gene expression in transgenic mice. Mol Imaging Biol 2002; 4:71-81.
140. Lee SY, Wang Z, Lin CK, et al. Regulation of intestine-specific spatiotemporal expression by the rat lactase promoter. J Biol Chem 2002; 277:13099-13105.
141. Zhang J, Tan X, Contag CH, et al. Dissection of promoter control modules that direct Bmp4 expression in the epithelium-derived components of hair follicles. Biochem Biophys Res Commun 2002; 293:1412-1419.
142. Zhang W, Feng JQ, Harris SE, et al. Rapid in vivo functional analysis of transgenes in mice using whole body imaging of luciferase expression. Transgenic Res 2001; 10:423-134.
143. Gross ME, Shazer RL, Agus DB. Targeting the HER-kinase axis in cancer. Semin Oncol 2004; 31:9-20.
144. Cai W, Niu G, Chen X. Multimodality imaging of the HER-kinase axis in cancer. Eur J Nucl Med Mol Imaging 2008; 35(1):186-208 [Epub 2007 September 11].
145. Niu G, Cai W, Chen X. Molecular imaging of human epidermal growth factor receptor 2 (HER-2) expression. Front Biosci 2008; 13:790-805.
146. Cai W, Chen K, He L, et al. Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody. Eur J Nucl Med Mol Imaging 2007; 34:850-858.
147. Sampath L, Kwon S, Ke S, et al. Dual-labeled trastuzumab-based imaging agent for the detection of human epidermal growth factor receptor 2 overexpression in breast cancer. J Nucl Med 2007; 48:1501-1510.
148. Villalobos V, Naik S, Piwnica-Worms D. Current state of imaging protein-protein interactions in vivo with genetically encoded reporters. Annu Rev Biomed Eng 2007; 9:321-349.
149. Ozawa T, Kaihara A, Sato M, et al. Split luciferase as an optical probe for detecting protein-protein interactions in mammalian cells based on protein splicing. Anal Chem 2001; 73:2516-2521.
150. Paulmurugan R, Gambhir SS. Monitoring protein-protein interactions using split synthetic renilla luciferase proteinfragment-assisted complementation. Anal Chem 2003; 75:1584-1589.
151. Luker GD, Sharma V, Pica CM, et al. Noninvasive imaging of protein-protein interactions in living animals. Proc Natl Acad Sci U S A 2002; 99:6961-6966.
152. Ray P, Pimenta H, Paulmurugan R, et al. Noninvasive quantitative imaging of protein-protein interactions in living subjects. Proc Natl Acad Sci U S A 2002; 99:3105-3110.
153. De A, Gambhir SS. Noninvasive imaging of proteinprotein interactions from live cells and living subjects using bioluminescence resonance energy transfer. FASEB J 2005; 19:2017-2019.
154. Thornberry NA, Lazebnik Y. Caspases: enemies within. Science 1998; 281:1312-1316.
155. Schmitt CA, Lowe SW. Apoptosis and therapy. J Pathol 1999; 187:127-137.
156. Laxman B, Hall DE, Bhojani MS, et al. Noninvasive realtime imaging of apoptosis. Proc Natl Acad Sci U S A 2002; 99:16551-16555.
157. Messerli SM, Prabhakar S, Tang Y, et al. A novel method for imaging apoptosis using a caspase-1 near-infrared fluorescent probe. Neoplasia 2004; 6:95-105.
158. Blankenberg FG, Katsikis PD, Tait JF, et al. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci U S A 1998; 95:6349-6354.
159. Mandl SJ, Mari C, Edinger M, et al. Multi-modality imaging identifies key times for annexin V imaging as an early predictor of therapeutic outcome. Mol Imaging 2004; 3:1-8.
160. Zhao M, Beauregard DA, Loizou L, et al. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nat Med 2001; 7:1241-1244.
161. Petrovsky A, Schellenberger E, Josephson L, et al. Near-infrared fluorescent imaging of tumor apoptosis. Cancer Res 2003; 63:1936-1942.
162. Schellenberger EA, Bogdanov A Jr., Petrovsky A, et al. Optical imaging of apoptosis as a biomarker of tumor response to chemotherapy. Neoplasia 2003; 5:187-192.
163. Chang J, Ormerod M, Powles TJ, et al. Apoptosis and proliferation as predictors of chemotherapy response in patients withbreastcarcinoma. Cancer2000; 89:2145-2152.
164. Weissleder R, Tung CH, Mahmood U, et al. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999; 17:375-378.
165. Tung CH, Mahmood U, Bredow S, et al. In vivo imaging of proteolytic enzyme activity using a novel molecular reporter. Cancer Res 2000; 60:4953-4958.
166. Gondi CS, Lakka SS, Yanamandra N, et al. Adenovirus-mediated expression of antisense urokinase plasminogen activator receptor and antisense cathepsin B inhibits tumor growth, invasion, and angiogenesis in gliomas. Cancer Res 2004; 64:4069-4077.
167. Wunder A, Tung CH, Muller-Ladner U, et al. In vivo imaging of protease activity in arthritis: a novel approach for monitoring treatment response. Arthritis Rheum 2004; 50:2459-2465.
168. Bremer C, Bredow S, Mahmood U, et al. Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model. Radiology 2001; 221:523-529.
169. Himmelreich U, Aime S, Hieronymus T, et al. A responsive MRI contrast agent to monitor functional cell status. Neuroimage 2006; 32:1142-1149.
170. Law B, Curino A, Bugge TH, et al. Design, synthesis, and characterization of urokinase plasminogen-activator-sensitive near-infrared reporter. Chem Biol 2004; 11:99-106.
171. Luker GD, Pica CM, Song J, et al. Imaging 26S protea-some activity and inhibition in living mice. Nat Med 2003; 9:969-973.
172. Gross S, Piwnica-Worms D. Monitoring proteasome activity in cellulo and in living animals by bioluminescent imaging: technical considerations for design and use of genetically encoded reporters. Methods Enzymol 2005; 399:512-530.
173. Sipkins DA, Cheresh DA, Kazemi MR, et al. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med 1998; 4:623-626.
174. Winter PM, Caruthers SD, Kassner A, et al. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res 2003; 63:5838-5843.
175. Lanza GM, Winter PM, Caruthers SD, et al. Magnetic resonance molecular imaging with nanoparticles. J Nucl Cardiol 2004; 11:733-743.
176. Haubner R, Wester HJ, Weber WA, et al. Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res 2001; 61:1781-1785.
177. Haubner R, Weber WA, Beer AJ, et al. Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F] Galacto-RGD. PLoS Med 2005; 2:e70.
178. Kang HW, Josephson L, Petrovsky A, et al. Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconjug Chem 2002; 13:122-127.
179. Kang HW, Weissleder R, Bogdanov A Jr. Targeting of MPEG-protected polyamino acid carrier to human E- selectin in vitro. Amino Acids 2002; 23:301-308.
180. Neri D, Carnemolla B, Nissim A, et al. Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform. Nat Biotech-nol 1997; 15:1271-1275.
181. Brower V. Tumor angiogenesis-new drugs on the block. Nat Biotechnol 1999; 17:963-968.
182. Pearson DA, Lister J, McBride WJ, et al. Thrombus imaging using technetium-99m-labeled high-potency GPIIb/IIIa receptor antagonists. Chemistry and initial biological studies. J Med Chem 1996; 39:1372-1382.
183. Bredow S, Lewin M, Hofmann B, et al. Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin. Eur J Cancer 2000; 36:675-681.
184. Anderson SA, Glod J, Arbab AS, et al. Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model. Blood 2005; 105:420-425.
185. Ferrari N, Glod J, Lee J, et al. Bone marrow-derived, endothelial progenitor-like cells as angiogenesis-selective gene-targeting vectors. Gene Ther 2003; 10:647-656.
186. Cai W, Chen X. Multimodality imaging of vascular endothelial growth factor and vascular endothelial growth factor receptor expression. Front Biosci 2007; 12:4267-4279.
187. Dove A. Cell-based therapies go live. Nat Biotechnol 2002; 20:339-343.
188. Gross S, Moss BL, Piwnica-Worms D. Veni, vidi, vici: in vivo molecular imaging of immune response. Immunity 2007; 27:533-538.
189. Koike C, Oku N, Watanabe M, et al. Real-time PET analysis of metastatic tumor cell trafficking in vivo and its relation to adhesion properties. Biochim Biophys Acta 1995; 1238:99-106.
190. Adonai N, Nguyen KN, Walsh J, et al. Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiose-micarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc Natl Acad Sci USA 2002; 99:3030-3035.
191. Hardy J, Edinger M, Bachmann MH, et al. Bioluminescence imaging of lymphocyte trafficking in vivo. Exp Hematol 2001; 29:1353-1360.
192. Kircher MF, Allport JR, Graves EE, et al. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res 2003; 63:6838-6846.
193. Papierniak CK, Bourey RE, Kretschmer RR, et al. Technetium-99m labeling of human monocytes for chemotactic studies. J Nucl Med 1976; 17:988-992.
194. Gobuty AH, Robinson RG, Barth RF. Organ distribution of 99mTc- and 51Cr-labeled autologous peripheral blood lymphocytes in rabbits. J Nucl Med 1977; 18:141-146.
195. Koehne G, Doubrovin M, Doubrovina E, et al. Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes. Nat Bio-technol 2003; 21:405-113.
196. Dubey P, Su H, Adonai N, et al. Quantitative imaging of the T cell antitumor response by positron-emission tomography. Proc Natl Acad Sci U S A 2003; 100:1232-1237.
197. Kim YJ, Dubey P, Ray P, et al. Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene. Mol Imaging Biol 2004; 6:331-340.
198. Garbossa D, Fontanella M, Fronda C, et al. New strategies for repairing the injured spinal cord: the role of stem cells. Neurol Res 2006; 28:500-504.
199. Schouten JW, Fulp CT, Royo NC, et al. A review and rationale for the use of cellular transplantation as a therapeutic strategy for traumatic brain injury. J Neurotrauma 2004; 21:1501-1538.
200. Karussis D, Kassis I. Use of stem cells for the treatment of multiple sclerosis. Expert Rev Neurother 2007; 7: 1189-1201.
201. Parish CL, Arenas E. Stem-cell-based strategies for the treatment of Parkinson's disease. Neurodegener Dis 2007; 4:339-347.
202. Walczak P, Bulte JW. The role of noninvasive cellular imaging in developing cell-based therapies for neurode-generative disorders. Neurodegener Dis 2007; 4:306-313.
203. Aboody KS, Brown A, Rainov NG, et al. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA 2000; 97:12846-12851.
204. Xu F, Zhu JH. Stem cells tropism for malignant gliomas. Neurosci Bull 2007; 23:363-369.
205. Hoehn M, Kustermann E, Blunk J, et al. Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci U S A 2002; 99:16267-16272.
206. Modo M, Mellodew K, Cash D, et al. Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study. Neuroimage 2004; 21:311-317.
207. Kim DE, Schellingerhout D, Ishii K, et al. Imaging of stem cell recruitment to ischemic infarcts in a murine model. Stroke 2004; 35:952-957.
208. Sheikh AY, Lin SA, Cao F, et al. Molecular imaging of bone marrow mononuclear cell homing and engraftment in ischemic myocardium. Stem Cells 2007; 25:2677-2684.
209. Hung SC, Deng WP, Yang WK, et al. Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging. Clin Cancer Res 2005; 11:7749-7756.
210. Zhang Z, Jiang Q, Jiang F, et al. In vivo magnetic resonance imaging tracks adult neural progenitor cell targeting of brain tumor. Neuroimage 2004; 23:281-287.
211. Miletic H, Fischer Y, Litwak S, et al. Bystander Killing of Malignant Glioma by Bone Marrow-derived Tumor-Infiltrating Progenitor Cells Expressing a Suicide Gene. Mol Ther 2007; 15:1373-1381.
212. Cao F, Drukker M, Lin S, et al. Molecular imaging of embryonic stem cell misbehavior and suicide gene ablation. Cloning Stem Cells 2007; 9:107-117.
213. Rueger MAAM. (18F)FLT-PET for non-invasive monitoring of experimental gliomas during antiproliferative therapy with suicide genes in vivo 2007 (in preparation) 2007.
214. Segura J, Fillat C, Andreu D, et al. Monitoring gene therapy by external imaging of mRNA: pilot study on murine erythropoietin. Ther Drug Monit 2007; 29:612-618.
215. Jacobs AH, Rueger MA, Winkeler A, et al. Imaging-guided gene therapy of experimental gliomas. Cancer Res 2007; 67:1706-1715.
216. Yan C, Wen-Chao L, Hong-Yan Q, et al. A new targeting approach for breast cancer gene therapy using the human fatty acid synthase promoter. Acta Oncol 2007; 46: 773-781.
217. Maatta AM, Korja S, Venhoranta H, et al. Transcriptional targeting of virus-mediated gene transfer by the human hexokinase II promoter. Int J Mol Med 2006; 18:901-908.
218. Mathis JM, Williams BJ, Sibley DA, et al. Cancer-specific targeting of an adenovirus-delivered herpes simplex virus thymidine kinase suicide gene using translational control. J Gene Med 2006; 8:1105-1120.