Abstract
Non-invasive in-vivo molecular genetic imaging developed over the past decade and predominantly utilises radiotracer (PET, gamma camera, autoradiography), magnetic resonance and optical imaging technology. Molecular genetic imaging has its roots in both molecular biology and cell biology. The convergence of these disciplines and imaging modalities has provided the opportunity to address new research questions, including oncogenesis, tumour maintenance and progression, as well as responses to molecular-targeted therapy. Three different imaging strategies are described: (1) “bio-marker” or “surrogate” imaging; (2) “direct” imaging of specific molecules and pathway activity; (3) “indirect” reporter gene imaging. Examples of each imaging strategy are presented and discussed. Several applications of PET- and optical-based reporter imaging are demonstrated, including signal transduction pathway monitoring, oncogenesis in genetic mouse models, endogenous molecular genetic/biological processes and the response to therapy in animal models of human disease. Molecular imaging studies will compliment established ex-vivo molecular-biological assays that require tissue sampling by providing a spatial and a temporal dimension to our understanding of disease development and progression, as well as response to treatment. Although molecular imaging studies are currently being performed primarily in experimental animals, we optimistically expect they will be translated to human subjects with cancer and other diseases in the near future.
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Keywords
- Positron Emission Tomography Imaging
- Reporter Gene Expression
- Bioluminescence Imaging
- Single Photon Emission Compute Tomogra
- Magnetic Reso Imaging
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Adonai N NK, Walsh J, Iyer M, Toyokuni T, Phelps ME, McCarthy T, McCarthy DW, Gambhir SS (2002) Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc Natl Acad Sci USA 99:3030–3035
Alauddin MM, Conti PS (1998) Synthesis and preliminary evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG): a new potential imaging agent for viral infection and gene therapy using PET. Nucl Med Biol 25:175–180
Altmann A, Kissel M, Zitzmann S, Kubler W, Mahmut M, Peschke P, Haberkorn U (2003) Increased MIBG uptake after transfer of the human norepinephrine transporter gene in rat hepatoma. J Nucl Med 44:973–980
Arbab AS, Yocum GT, Rad AM, Khakoo AY, Fellowes V, Read EJ, Frank JA (2005) Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed 18:553–559
Arbab AS, Yocum GT, Kalish H, Jordan EK, Anderson SA, Khakoo AY, Read EJ, Frank JA (2004) Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood 104:1217–1223
Artemov D, Mori N, Ravi R, Bhujwalla ZM (2003) Magnetic resonance molecular imaging of the HER-2/neu receptor. Cancer Res 63:2723–2727
Bachtiary B, Schindl M, Potter R, Dreier B, Knocke TH, Hainfellner JA, Horvat R, Birner P (2003) Overexpression of hypoxia-inducible factor 1alpha indicates diminished response to radiotherapy and unfavorable prognosis in patients receiving radical radiotherapy for cervical cancer. Clin Cancer Res 9:2234–2240
Berger F, Gambhir SS (2001) Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer. Breast Cancer Res 3:28–35
Bhaumik S, Gambhir SS (2002) Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc Natl Acad Sci USA 99:377–382
Blasberg RG, Gelovani J (2002) Molecular-genetic imaging: a nuclear medicine-based perspective. Mol Imaging 1:280–300
Blasberg RG, Tjuvajev JG (2003) Molecular-genetic imaging: current and future perspectives. J Clin Invest 111:1620–1629
Blend MJ, Stastny JJ, Swanson SM, Brechbiel MW (2003) Labeling anti-HER2/neu monoclonal antibodies with 111In and 90Y using a bifunctional DTPA chelating agent. Cancer Biother Radiopharm 18:355–363
Boland A, Ricard M, Opolon P, Bidart JM, Yeh P, Filetti S, Schlumberger M, Perricaudet M (2000) Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy. Cancer Res 60:3484–3492
Bradley J, Thorstad WL, Mutic S, Miller TR, Dehdashti F, Siegel BA, Bosch W, Bertrand RJ (2004) Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 59:78–86
Brennan P, Babbage JW, Burgering BM, Groner B, Reif K, Cantrell DA (1997) Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Immunity 7:679–689
Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Bean JM, Prosnitz LR, Dewhirst MW (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941–943
Brown RS, Leung JY, Fisher SJ, Frey KA, Ethier SP, Wahl RL (1996) Intratumoral distribution of tritiated-FDG in breast carcinoma: correlation between Glut-1 expression and FDG uptake. J Nucl Med 37:1042–1047
Brun NC, Moen A, Borch K, Saugstad OD, Greisen G (1997) Near-infrared monitoring of cerebral tissue oxygen saturation and blood volume in newborn piglets. Am J Physiol 273:H682–H686
Bulte JW, Arbab AS, Douglas T, Frank JA (2004) Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging. Methods Enzymol 386:275–299
Cammilleri S, Sangrajrang S, Perdereau B, Brixy F, Calvo F, Bazin H, Magdelenat H (1996) Biodistribution of iodine-125 tyramine transforming growth factor alpha antisense oligonucleotide in athymic mice with a human mammary tumour xenograft following intratumoral injection. Eur J Nucl Med 23:448–452
Campbell RE, Tour O, Palmer AE, Steinbach PA, Baird GS, Zacharias DA, Tsien RY (2002) A monomeric red fluorescent protein. Proc Natl Acad Sci USA 99:7877–7882
Cao YA, Wagers AJ, Beilhack A, Dusich J, Bachmann MH, Negrin RS, Weissman IL, Contag CH (2004) Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc Natl Acad Sci USA 101:221–226
Chapman JD, Baer K, Lee J (1983) Characteristics of the metabolism-induced binding of misonidazole to hypoxic mammalian cells. Cancer Res 43:1523–1528
Che J, Doubrovin M, Serganova I, Ageyeva L, Zanzonico P, Blasberg R (2005) hNIS-IRES-eGFP dual reporter gene imaging. Mol Imaging 4:128–136
Chievitz O and Hevesy G (1935) Radioactive indicators in the study of phosphorous metabolism in rats. Nature 136:754–755
Chishima T, Miyagi Y, Wang X, Yamaoka H, Shimada H, Moossa AR, Hoffman RM (1997) Cancer invasion and micrometastasis visualized in live tissue by green fluorescent protein expression. Cancer Res 57:2042–2047
Chudakov DM, Verkhusha VV, Staroverov DB, Souslova EA, Lukyanov S, Lukyanov KA (2004) Photoswitchable cyan fluorescent protein for protein tracking. Nat Biotechnol 22:1435–1439
Colpaert CG, Vermeulen PB, Fox SB, Harris AL, Dirix LY, Van Marck EA (2003) The presence of a fibrotic focus in invasive breast carcinoma correlates with the expression of carbonic anhydrase IX and is a marker of hypoxia and poor prognosis. Breast Cancer Res Treat 81:137–147
Contag CH, Spilman SD, Contag PR, Oshiro M, Eames B, Dennery P, Stevenson DK, Benaron DA (1997) Visualizing gene expression in living mammals using a bioluminescent reporter. Photochem Photobiol 66:523–531
Contag PR, Olomu IN, Stevenson DK, Contag CH (1998) Bioluminescent indicators in living mammals. Nat Med 4:245–247
Contag CH, Ross BD (2002) It’s not just about anatomy: in vivo bioluminescence imaging as an eyepiece into biology. J Magn Reson Imaging 16:378–387
Cooper R, Sarioglu S, Sokmen S, Fuzun M, Kupelioglu A, Valentine H, Gorken IB, Airley R, West C (2003) Glucose transporter-1 (GLUT-1): a potential marker of prognosis in rectal carcinoma? Br J Cancer 89:870–876
Costa GL SM, Nakajima A, Nguyen EV, Taylor-Edwards C, Slavin AJ, Contag CH, Fathman CG, Benson JM (2001) Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit. J Immunol 167:2379–2387
Dai C, Celestino JC, Okada Y, Louis DN, Fuller GN, Holland EC (2001) PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev 15:1913–1925
Dai G, Levy O, Carrasco N (1996) Cloning and characterization of the thyroid iodide transporter. Nature 379:458–460
Dehdashti F, Mortimer JE, Siegel BA, Griffeth LK, Bonasera TJ, Fusselman MJ, Detert DD, Cutler PD, Katzenellenbogen JA, Welch MJ (1995) Positron tomographic assessment of estrogen receptors in breast cancer: comparison with FDG-PET and in vitro receptor assays. J Nucl Med 36:1766–1774
Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472–480
Dewanjee MK, Ghafouripour AK, Kapadvanjwala M, Dewanjee S, Serafini AN, Lopez DM, Sfakianakis GN (1994) Noninvasive imaging of c-myc oncogene messenger RNA with indium-111-antisense probes in a mammary tumor-bearing mouse model. J Nucl Med 35:1054–1063
Di Chiro G, DeLaPaz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, Patronas NJ, Kufta CV, Kessler RM, Johnston GS, Manning RG, Wolf AP (1982) Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography. Neurology 32:1323–1329
Dodd CH, Hsu HC, Chu WJ, Yang P, Zhang HG, Mountz JD Jr, Zinn K, Forder J, Josephson L, Weissleder R, Mountz JM, Mountz JD (2001) Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles. J Immunol Methods 256:89–105
Doubrovin M, Ponomarev V, Beresten T, Balatoni J, Bornmann W, Finn R, Humm J, Larson S, Sadelain M, Blasberg R, Gelovani Tjuvajev J (2001) Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci USA 98:9300–9305
Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2:561–566
Edinger M, Cao YA, Hornig YS, Jenkins DE, Verneris MR, Bachmann MH, Negrin RS, Contag CH (2002) Advancing animal models of neoplasia through in vivo bioluminescence imaging. Eur J Cancer 38:2128–2136
Elas M, Williams BB, Parasca A, Mailer C, Pelizzari CA, Lewis MA, River JN, Karczmar GS, Barth ED, Halpern HJ (2003) Quantitative tumor oxymetric images from 4D electron paramagnetic resonance imaging (EPRI): methodology and comparison with blood oxygen level-dependent (BOLD) MRI. Magn Reson Med 49:682–691
Ellenberg J, Lippincott-Schwartz J, Presley JF (1999) Dual-colour imaging with GFP variants. Trends Cell Biol 9:52–56
Evans SM, Kachur AV, Shiue CY, Hustinx R, Jenkins WT, Shive GG, Karp JS, Alavi A, Lord EM, Dolbier WR, Jr., Koch CJ (2000) Noninvasive detection of tumor hypoxia using the 2-nitroimidazole [18F]EF1. J Nucl Med 41:327–336
Evans SM, Judy KD, Dunphy I, Jenkins WT, Nelson PT, Collins R, Wileyto EP, Jenkins K, Hahn SM, Stevens CW, Judkins AR, Phillips P, Geoerger B, Koch CJ (2004) Comparative measurements of hypoxia in human brain tumors using needle electrodes and EF5 binding. Cancer Res 64:1886–1892
Falk MM, Lauf U (2001) High resolution, fluorescence deconvolution microscopy and tagging with the autofluorescent tracers CFP, GFP, and YFP to study the structural composition of gap junctions in living cells. Microsc Res Tech 52:251–262
Forss-Petter S, Danielson PE, Catsicas S, Battenberg E, Price J, Nerenberg M, Sutcliffe JG (1990) Transgenic mice expressing beta-galactosidase in mature neurons under neuron-specific enolase promoter control. Neuron 5:187–197
Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC, Plas DR, Elstrom RL, June CH, Thompson CB (2002) The CD28 signaling pathway regulates glucose metabolism. Immunity 16:769–777
Funovics MA, Kapeller B, Hoeller C, Su HS, Kunstfeld R, Puig S, Macfelda K (2004) MR imaging of the her2/neu and 9.2.27 tumor antigens using immunospecific contrast agents. Magn Reson Imaging 22:843–850
Fyfe JA, Keller PM, Furman PA, Miller RL, Elion GB (1978) Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. J Biol Chem 253:8721–8727
Gallardo HF, Tan C, Ory D, Sadelain M (1997) Recombinant retroviruses pseudotyped with the vesicular stomatitis virus G glycoprotein mediate both stable gene transfer and pseudotransduction in human peripheral blood lymphocytes. Blood 90:952–957
Gambhir SS (2002) Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2:683–693
Gambhir SS, Barrio JR, Wu L, Iyer M, Namavari M, Satyamurthy N, Bauer E, Parrish C, MacLaren DC, Borghei AR, Green LA, Sharfstein S, Berk AJ, Cherry SR, Phelps ME, Herschman HR (1998) Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir. J Nucl Med 39:2003–2011
Gambhir SS, Barrio JR, Phelps ME, Iyer M, Namavari M, Satyamurthy N, Wu L, Green LA, Bauer E, MacLaren DC, Nguyen K, Berk AJ, Cherry SR, Herschman HR (1999) Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. Proc Natl Acad Sci USA 96:2333–2338
Gambhir SS, Bauer E, Black ME, Liang Q, Kokoris MS, Barrio JR, Iyer M, Namavari M, Phelps ME, Herschman HR (2000a) 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 97:2785–2790
Gambhir SS, Herschman HR, Cherry SR, Barrio JR, Satyamurthy N, Toyokuni T, Phelps ME, Larson SM, Balatoni J, Finn R, Sadelain M, Tjuvajev J, Blasberg R (2000b) Imaging transgene expression with radionuclide imaging technologies. Neoplasia 2:118–138
Gelovani Tjuvajev J, Blasberg RG (2003) In vivo imaging of molecular-genetic targets for cancer therapy. Cancer Cell 3:327–332
Giatromanolaki A, Koukourakis MI, Sivridis E, Pastorek J, Wykoff CC, Gatter KC, Harris AL (2001) Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer. Cancer Res 61:7992–7998
Gillies RJ, Raghunand N, Karczmar GS, Bhujwalla ZM (2002) MRI of the tumor microenvironment. J Magn Reson Imaging 16:430–450
Gobuty AH RR, Barth RF (1977) Organ distribution of 99mTc- and 51Cr-labeled autologous peripheral blood lymphocytes in rabbits. J Nucl Med 18: 141–146
Green LA, Yap CS, Nguyen K, Barrio JR, Namavari M, Satyamurthy N, Phelps ME, Sandgren EP, Herschman HR, Gambhir SS (2002) Indirect monitoring of endogenous gene expression by positron emission tomography (PET) imaging of reporter gene expression in transgenic mice. Mol Imaging Biol 4:71–81
Gupta AK, Hutchinson PJ, Fryer T, Al-Rawi PG, Parry DA, Minhas PS, Kett-White R, Kirkpatrick PJ, Mathews JC, Downey S, Aigbirhio F, Clark J, Pickard JD, Menon DK (2002) Measurement of brain tissue oxygenation performed using positron emission tomography scanning to validate a novel monitoring method. J Neurosurg 96:263–268
Gurskaya NG, Fradkov AF, Terskikh A, Matz MV, Labas YA, Martynov VI, Yanushevich YG, Lukyanov KA, Lukyanov SA (2001) GFP-like chromoproteins as a source of far-red fluorescent proteins. FEBS Lett 507:16–20
Haberkorn U (2001) Gene therapy with sodium/iodide symporter in hepatocarcinoma. Exp Clin Endocrinol Diabetes 109:60–62
Hadjantonakis AK, Nagy A (2001) The color of mice: in the light of GFP-variant reporters. Histochem Cell Biol 115:49–58
Hadjantonakis AK, Macmaster S, Nagy A (2002) Embryonic stem cells and mice expressing different GFP variants for multiple non-invasive reporter usage within a single animal. BMC Biotechnol 2:11
Hagani AB RI, Tan C, Krause A, Sadelain M (1999) Activation conditions determine susceptibility of murine primary T-lymphocytes to retroviral infection. J Gene Med 1:341–351
Hain SF, Maisey MN (2003) Positron emission tomography for urological tumours. BJU Int 92:159–164
Halbhuber KJ, Konig K (2003) Modern laser scanning microscopy in biology, biotechnology and medicine. Ann Anat 185:1–20
Hardy J EM, Bachmann MH, Negrin RS, Fathman CG, Contag CH (2001) Bioluminescence imaging of lymphocyte trafficking in vivo. Exp Hematol 29:1353–1360
Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, de la Rosette J, Weissleder R (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491–2499
Harrington KJ, Linardakis E, Vile RG (2000) Transcriptional control: an essential component of cancer gene therapy strategies? Adv Drug Deliv Rev 44:167–184
Haubner R, Wester HJ, Weber WA, Mang C, Ziegler SI, Goodman SL, Senekowitsch-Schmidtke R, Kessler H, Schwaiger M (2001) Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res 61:1781–1785
Hennig J, Speck O, Koch MA, Weiller C (2003) Functional magnetic resonance imaging: a review of methodological aspects and clinical applications. J Magn Reson Imaging 18:1–15
Hill JM, Dick AJ, Raman VK, Thompson RB, Yu ZX, Hinds KA, Pessanha BS, Guttman MA, Varney TR, Martin BJ, Dunbar CE, McVeigh ER, Lederman RJ (2003) Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 108:1009–1014
Hinds KA, Hill JM, Shapiro EM, Laukkanen MO, Silva AC, Combs CA, Varney TR, Balaban RS, Koretsky AP, Dunbar CE (2003) Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. Blood 102:867–872
Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515
Hoehn M, Kustermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Focking M, Arnold H, Hescheler J, Fleischmann BK, Schwindt W, Buhrle C (2002) 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 99:16267–16272
Hoekstra CJ, Stroobants SG, Hoekstra OS, Vansteenkiste J, Biesma B, Schramel FJ, van Zandwijk N, van Tinteren H, Smit EF (2003) The value of [18F]fluoro-2-deoxy-D-glucose positron emission tomography in the selection of patients with stage IIIA-N2 non-small cell lung cancer for combined modality treatment. Lung Cancer 39:151–157
Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5: 796–806
Holland E (2004a) Mouse models of human cancer. Wiley-Liss, New York
Holland EC (2004b) Mouse models of human cancer as tools in drug development. Cancer Cell 6:197–198
Ichikawa T, Hogemann D, Saeki Y, Tyminski E, Terada K, Weissleder R, Chiocca EA, Basilion JP (2002) MRI of transgene expression: correlation to therapeutic gene expression. Neoplasia 4:523–530
Iida H, Rhodes CG, Araujo LI, Yamamoto Y, de Silva R, Maseri A, Jones T (1996) Noninvasive quantification of regional myocardial metabolic rate for oxygen by use of 15O2 inhalation and positron emission tomography. Theory, error analysis, and application in humans. Circulation 94:792–807
Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG, Jr. (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464–468
Iyer M, Barrio JR, Namavari M, Bauer E, Satyamurthy N, Nguyen K, Toyokuni T, Phelps ME, Herschman HR, Gambhir SS (2001a) 8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET. J Nucl Med 42:96–105
Iyer M, Wu L, Carey M, Wang Y, Smallwood A, Gambhir SS (2001b) Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters. Proc Natl Acad Sci USA 98:14595–14600
Jacobs A, Tjuvajev JG, Dubrovin M, Akhurst T, Balatoni J, Beattie B, Joshi R, Finn R, Larson SM, Herrlinger U, Pechan PA, Chiocca EA, Breakefield XO, Blasberg RG (2001a) Positron emission tomography-based imaging of transgene expression mediated by replication-conditional, oncolytic herpes simplex virus type 1 mutant vectors in vivo. Cancer Res 61:2983–2995
Jacobs A, Voges J, Reszka R, Lercher M, Gossmann A, Kracht L, Kaestle C, Wagner R, Wienhard K, Heiss WD (2001b) Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 358:727–729
Jacobs RE AE, Meade TJ, Fraser SE (1999) Looking deeper into vertebrate development. Trends Cell Biol 9:73–76
Jaffer FA, Tung CH, Gerszten RE, Weissleder R (2002) In vivo imaging of thrombin activity in experimental thrombi with thrombin-sensitive near-infrared molecular probe. Arterioscler Thromb Vasc Biol 22:1929–1935
Johnson GA BH, Black RD, Hedlund LW, Maronpot RR, Smith BR (1993) Histology by magnetic resonance microscopy. Magn Reson Q 9:1–30
Kaelin WG Jr (2005) The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing. Biochem Biophys Res Commun 338:627–638
Kelly RF, Tran T, Holmstrom A, Murar J, Segurola RJ, Jr. (2004) Accuracy and cost-effectiveness of [18F]-2-fluoro-deoxy-D-glucose-positron emission tomography scan in potentially resectable non-small cell lung cancer. Chest 125:1413–1423
Kiani A RA, Aramburu J (2000) Manipulating immune responses with immunosuppressive agents that target NFAT. Immunity 12:359–372
Kircher MF AJ, Graves EE, Love V, Josephson L, Lichtman AH, Weissleder R (2003) In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res 63:6838–6846
Koch CJ, Evans SM (2003) Non-invasive PET and SPECT imaging of tissue hypoxia using isotopically labeled 2-nitroimidazoles. Adv Exp Med Biol 510:285–292
Koehne G, Doubrovin, M, Doubrovina, E, Zanzonico, P, Gallardo, HF, Ivanova, A, Balatoni, J, Teruya-Feldstein, J, Heller, G, May, C, Ponomarev, V, Ruan, S, Finn, R, Blasberg, RG, Bornmann, W, Riviere, I, Sadelain, M, O’Reilly, RJ, Larson, SM, Gelovani Tjuvajev, JG. (2003) Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes. Nat Biotechnol 21:405–413
Kolb VA, Makeyev EV, Spirin AS (2000) Co-translational folding of an eukaryotic multidomain protein in a prokaryotic translation system. J Biol Chem 275:16597–16601
Korf J V-vdDL, Brinkman-Medema R, Niemarkt A, de Leij LF (1998) Divalent cobalt as a label to study lymphocyte distribution using PET and SPECT. J Nucl Med 39:836–841
Kostura L, Kraitchman DL, Mackay AM, Pittenger MF, Bulte JW (2004) Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 17:513–517
Krishna MC, Subramanian S, Kuppusamy P, Mitchell JB (2001) Magnetic resonance imaging for in vivo assessment of tissue oxygen concentration. Semin Radiat Oncol 11:58–69
Labas YA, Gurskaya NG, Yanushevich YG, Fradkov AF, Lukyanov KA, Lukyanov SA, Matz MV (2002) Diversity and evolution of the green fluorescent protein family. Proc Natl Acad Sci USA 99:4256–4261
Lalwani AK, Han JJ, Walsh BJ, Zolotukhin S, Muzyczka N, Mhatre AN (1997) Green fluorescent protein as a reporter for gene transfer studies in the cochlea. Hear Res 114:139–147
Larson SM, Morris M, Gunther I, Beattie B, Humm JL, Akhurst TA, Finn RD, Erdi Y, Pentlow K, Dyke J, Squire O, Bornmann W, McCarthy T, Welch M, Scher H (2004) Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. J Nucl Med 45:366–373
Laxman B, Hall DE, Bhojani MS, Hamstra DA, Chenevert TL, Ross BD, Rehemtulla A (2002) Noninvasive real-time imaging of apoptosis. Proc Natl Acad Sci USA 99:16551–16555
Lazar-Molnar E, Hegyesi H, Toth S, Falus A (2000) Autocrine and paracrine regulation by cytokines and growth factors in melanoma. Cytokine 12:547–554
Lee KH, Kim HK, Paik JY, Matsui T, Choe YS, Choi Y, Kim BT (2005) Accuracy of myocardial sodium/iodide symporter gene expression imaging with radioiodide: evaluation with a dual-gene adenovirus vector. J Nucl Med 46:652–657
Lehtio K, Eskola O, Viljanen T, Oikonen V, Gronroos T, Sillanmaki L, Grenman R, Minn H (2004) Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer. Int J Radiat Oncol Biol Phys 59:971–982
Levy JP, Muldoon RR, Zolotukhin S, Link CJ, Jr. (1996) Retroviral transfer and expression of a humanized, red-shifted green fluorescent protein gene into human tumor cells. Nat Biotechnol 14:610–614
Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, Weissleder R (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18 410–414
Lewis JS, Welch MJ (2001) PET imaging of hypoxia. Q J Nucl Med 45:183–188
Li W HR (1996) Regulation of the nuclear factor of activated T cells in stably transfected Jurkat cell clones. Biochem Biophys Res Commun 219:96–99
Liang Q, Satyamurthy N, Barrio JR, Toyokuni T, Phelps MP, Gambhir SS, Herschman HR (2001) Noninvasive, quantitative imaging in living animals of a mutant dopamine D2 receptor reporter gene in which ligand binding is uncoupled from signal transduction. Gene Ther 8:1490–1498
Loncaster JA, Harris AL, Davidson SE, Logue JP, Hunter RD, Wycoff CC, Pastorek J, Ratcliffe PJ, Stratford IJ, West CM (2001) Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res 61:6394–6399
Louie AY, Huber MM, Ahrens ET, Rothbacher U, Moats R, Jacobs RE, Fraser SE, Meade TJ (2000) In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 18:321–325
Luker GD, Sharma V, Pica CM, Dahlheimer JL, Li W, Ochesky J, Ryan CE, Piwnica-Worms H, Piwnica-Worms D (2002) Noninvasive imaging of protein-protein interactions in living animals. Proc Natl Acad Sci USA 99:6961–6966
Luker GD, Pica CM, Song J, Luker KE, Piwnica-Worms D (2003a) Imaging 26S proteasome activity and inhibition in living mice. Nat Med 9:969–973
Luker GD, Sharma V, Pica CM, Prior JL, Li W, Piwnica-Worms D (2003b) Molecular imaging of protein-protein interactions: controlled expression of p53 and large T-antigen fusion proteins in vivo. Cancer Res 63:1780–1788
Luker GD, Sharma V, Piwnica-Worms D (2003c) Visualizing protein-protein interactions in living animals. Methods 29:110–122
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139
Lyons SK, Meuwissen R, Krimpenfort P, Berns A (2003) The generation of a conditional reporter that enables bioluminescence imaging of Cre/loxP-dependent tumorigenesis in mice. Cancer Res 63:7042–7046
Lyons SK, Lim E, Clermont AO, Dusich J, Zhu L, Campbell KD, Coffee RJ, Grass DS, Hunter J, Purchio T, Jenkins D (2006) Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice. Cancer Res 66:4701–4707
Maschauer S, Prante O, Hoffmann M, Deichen JT, Kuwert T (2004) Characterization of 18F-FDG uptake in human endothelial cells in vitro. J Nucl Med 45:455–460
Mathieu S, El-Battari A (2003) Monitoring E-selectin-mediated adhesion using green and red fluorescent proteins. J Immunol Methods 272:81–92
Matz MV, Fradkov AF, Labas YA, Savitsky AP, Zaraisky AG, Markelov ML, Lukyanov SA (1999) Fluorescent proteins from nonbioluminescent Anthozoa species. Nat Biotechnol 17:969–973
Mayer-Kuckuk P, Banerjee D, Malhotra S, Doubrovin M, Iwamoto M, Akhurst T, Balatoni J, Bornmann W, Finn R, Larson S, Fong Y, Gelovani Tjuvajev J, Blasberg R, Bertino JR (2002) Cells exposed to antifolates show increased cellular levels of proteins fused to dihydrofolate reductase: a method to modulate gene expression. Proc Natl Acad Sci USA 99:3400–3405
Mayer-Kuckuk P, Menon LG, Blasberg RG, Bertino JR, Banerjee D (2004) Role of reporter gene imaging in molecular and cellular biology. Biol Chem 385:353–361
Mayer-Kuckuk P, Doubrovin M, Bidaut L, Budak-Alpdogan T, Cai S, Hubbard V, Alpdogan O, van den Brink M, Bertino JR, Blasberg RG, Banerjee D, Gelovani J (2006) Molecular imaging reveals skeletal engraftment sites of transplanted bone marrow cells. Cell Transplant 15:75–82
Min JJ, Gambhir SS (2004) Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects. Gene Ther 11:115–125
Min JJ, Iyer M, Gambhir SS (2003) Comparison of [18F]FHBG and [14C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection. Eur J Nucl Med Mol Imaging 30:1547–1560
Moberg KH, Logan TJ, Tyndall WA, Hall DJ (1992) Three distinct elements within the murine c-myc promoter are required for transcription. Oncogene 7:411–421
Myers WG (1979) Georg Charles de Hevesy: the father of nuclear medicine. J Nucl Med 20: 590–594
Nakagawa S, Massie B, Hawley RG (2001) Tetracycline-regulatable adenovirus vectors: pharmacologic properties and clinical potential. Eur J Pharm Sci 13:53–60
Neckers L (2002) Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 8:S55–S61
Neumaier M, Shively L, Chen FS, Gaida FJ, Ilgen C, Paxton RJ, Shively JE, Riggs AD (1990) Cloning of the genes for T84.66, an antibody that has a high specificity and affinity for carcinoembryonic antigen, and expression of chimeric human/mouse T84.66 genes in myeloma and Chinese hamster ovary cells. Cancer Res 50:2128–2134
Nordsmark M, Overgaard M, Overgaard J (1996) Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 41:31–39
Nordsmark M, Loncaster J, Aquino-Parsons C, Chou SC, Ladekarl M, Havsteen H, Lindegaard JC, Davidson SE, Varia M, West C, Hunter R, Overgaard J, Raleigh JA (2003) Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas. Radiother Oncol 67:35–44
Olafsen T, Kenanova VE, Sundaresan G, Anderson AL, Crow D, Yazaki PJ, Li L, Press MF, Gambhir SS, Williams LE, Wong JY, Raubitschek AA, Shively JE, Wu AM (2005) Optimizing radiolabeled engineered anti-p185HER2 antibody fragments for in vivo imaging. Cancer Res 65:5907–5916
Olasz EB, Lang L, Seidel J, Green MV, Eckelman WC, Katz SI (2002) Fluorine-18 labeled mouse bone marrow-derived dendritic cells can be detected in vivo by high resolution projection imaging. J Immunol Methods 260:137–148
Oliver RJ, Woodwards RT, Sloan P, Thakker NS, Stratford IJ, Airley RE (2004) Prognostic value of facilitative glucose transporter Glut-1 in oral squamous cell carcinomas treated by surgical resection; results of EORTC Translational Research Fund studies. Eur J Cancer 40:503–507
Oswald F, Lovec H, Moroy T, Lipp M (1994) E2F-dependent regulation of human MYC: trans-activation by cyclins D1 and A overrides tumour suppressor protein functions. Oncogene 9:2029–2036
Overbeek PA, Chepelinsky AB, Khillan JS, Piatigorsky J, Westphal H (1985) Lens-specific expression and developmental regulation of the bacterial chloramphenicol acetyltransferase gene driven by the murine alpha A-crystallin promoter in transgenic mice. Proc Natl Acad Sci USA 82:7815–7819
Palm S, Enmon RM, Jr., Matei C, Kolbert KS, Xu S, Zanzonico PB, Finn RL, Koutcher JA, Larson SM, Sgouros G (2003) Pharmacokinetics and Biodistribution of (86)Y-Trastuzumab for (90)Y dosimetry in an ovarian carcinoma model: correlative MicroPET and MRI. J Nucl Med 44:1148–1155
Papadakis ED, Nicklin SA, Baker AH, White SJ (2004) Promoters and control elements: designing expression cassettes for gene therapy. Curr Gene Ther 4:89–113
Papierniak CK BR, Kretschmer RR, Gotoff SP, Colombetti LG (1976) Technetium-99m labeling of human monocytes for chemotactic studies. J Nucl Med 17:988–992
Peng T, Golub TR, Sabatini DM (2002) The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation. Mol Cell Biol 22:5575–5584
Penuelas I, Mazzolini G, Boan JF, Sangro B, Marti-Climent J, Ruiz M, Ruiz J, Satyamurthy N, Qian C, Barrio JR, Phelps ME, Richter JA, Gambhir SS, Prieto J (2005) Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology 128:1787–1795
Phillips JA, Craig SJ, Bayley D, Christian RA, Geary R, Nicklin PL (1997) Pharmacokinetics, metabolism, and elimination of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A) after intravenous and subcutaneous administration. Biochem Pharmacol 54:657–668
Pichler A, Prior JL, Piwnica-Worms D (2004) Imaging reversal of multidrug resistance in living mice with bioluminescence: MDR1 P-glycoprotein transports coelenterazine. Proc Natl Acad Sci USA 101:1702–1707
Ponomarev V, Doubrovin M, Lyddane C, Beresten T, Balatoni J, Bornman W, Finn R, Akhurst T, Larson S, Blasberg R, Sadelain M, Tjuvajev JG (2001) Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. Neoplasia 3:480–488
Ponomarev V, Doubrovin M, Serganova I, Beresten T, Vider J, Shavrin A, Ageyeva L, Balatoni J, Blasberg R, Tjuvajev JG (2003) Cytoplasmically retargeted HSV1-tk/GFP reporter gene mutants for optimization of noninvasive molecular-genetic imaging. Neoplasia 5:245–254
Ponomarev V, Doubrovin M, Serganova I, Vider J, Shavrin A, Beresten T, Ivanova A, Ageyeva L, Tourkova V, Balatoni J, Bornmann W, Blasberg R, Gelovani Tjuvajev J (2004) A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging. Eur J Nucl Med Mol Imaging 31:740–751
Qiao J, Doubrovin M, Sauter BV, Huang Y, Guo ZS, Balatoni J, Akhurst T, Blasberg RG, Tjuvajev JG, Chen SH, Woo SL (2002) Tumor-specific transcriptional targeting of suicide gene therapy. Gene Ther 9: 168–175
Rannie GH TM, Ford WL (1977) An experimental comparison of radioactive labels with potential application to lymphocyte migration studies in patients. Clin Exp Immunol 29: 509–514
Rasey JS, Koh WJ, Evans ML, Peterson LM, Lewellen TK, Graham MM, Krohn KA (1996) Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 36:417–428
Ray P, Bauer E, Iyer M, Barrio JR, Satyamurthy N, Phelps ME, Herschman HR, Gambhir SS (2001) Monitoring gene therapy with reporter gene imaging. Semin Nucl Med 31:312–320
Ray P, Pimenta H, Paulmurugan R, Berger F, Phelps ME, Iyer M, Gambhir SS (2002) Noninvasive quantitative imaging of protein-protein interactions in living subjects. Proc Natl Acad Sci USA 99:3105–3110
Ray P, Wu AM, Gambhir SS (2003) Optical bioluminescence and positron emission tomography imaging of a novel fusion reporter gene in tumor xenografts of living mice. Cancer Res 63:1160–1165
Ray S, Paulmurugan R, Hildebrandt I, Iyer M, Wu L, Carey M, Gambhir SS (2004) Novel bidirectional vector strategy for amplification of therapeutic and reporter gene expression. Hum Gene Ther 15:681–690
Rehemtulla A, Stegman LD, Cardozo SJ, Gupta S, Hall DE, Contag CH, Ross BD (2000) Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia 2:491–495
Rogers BE, Zinn KR, Buchsbaum DJ (2000) Gene transfer strategies for improving radiolabeled peptide imaging and therapy. Q J Nucl Med 44:208–223
Sadeghi H, Hitt MM (2005) Transcriptionally targeted adenovirus vectors. Curr Gene Ther 5: 411–427
Salceda S, Caro J (1997) Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem 272:22642–22647
Schelling M, Avril N, Nahrig J, Kuhn W, Romer W, Sattler D, Werner M, Dose J, Janicke F, Graeff H, Schwaiger M (2000) Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 18:1689–1695
Serganova I, Doubrovin M, Vider J, Ponomarev V, Soghomonyan S, Beresten T, Ageyeva L, Serganov A, Cai S, Balatoni J, Blasberg R, Gelovani J (2004) Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. Cancer Res 64:6101–6108
Shah K, Jacobs A, Breakefield XO, Weissleder R (2004) Molecular imaging of gene therapy for cancer. Gene Ther 11:1175–1187
Shaner NC, Steinbach PA, Tsien RY (2005) A guide to choosing fluorescent proteins. Nat Methods 2:905–909
Shaner NC, Campbell RE, Steinbach PA, Giepmans BN, Palmer AE, Tsien RY (2004) Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol 22:1567–1572
Sherr CJ, McCormick F (2002) The RB and p53 pathways in cancer. Cancer Cell 2:103–112
Shin JH, Chung JK, Kang JH, Lee YJ, Kim KI, So Y, Jeong JM, Lee DS, Lee MC (2004) Noninvasive imaging for monitoring of viable cancer cells using a dual-imaging reporter gene. J Nucl Med 45:2109–2115
Shreve PD, Anzai Y, Wahl RL (1999) Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics 19:61–77; quiz 150–151
Smith-Jones PM, Solit DB, Akhurst T, Afroze F, Rosen N, Larson SM (2004) Imaging the pharmacodynamics of HER2 degradation in response to Hsp90 inhibitors. Nat Biotechnol 22:701–706
Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361:45–46
Su H FA, Gambhir SS, Braun J (2004) Quantitation of cell number by a positron emission tomography reporter gene strategy. Mol Imaging Biol 6:139–148
Sundaresan G, Yazaki PJ, Shively JE, Finn RD, Larson SM, Raubitschek AA, Williams LE, Chatziioannou AF, Gambhir SS, Wu AM (2003) 124I-labeled engineered anti-CEA minibodies and diabodies allow high-contrast, antigen-specific small-animal PET imaging of xenografts in athymic mice. J Nucl Med 44:1962–1969
Tavitian B (2000) In vivo antisense imaging. Q J Nucl Med 44:236–255
Tavitian B, Terrazzino S, Kuhnast B, Marzabal S, Stettler O, Dolle F, Deverre JR, Jobert A, Hinnen F, Bendriem B, Crouzel C, Di Giamberardino L (1998) In vivo imaging of oligonucleotides with positron emission tomography. Nat Med 4:467–471
Thomas GV, Tran C, Mellinghoff IK, Welsbie DS, Chan E, Fueger B, Czernin J, Sawyers CL (2006) Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med 12:122–127
Thompson JF, Hayes LS, Lloyd DB (1991) Modulation of firefly luciferase stability and impact on studies of gene regulation. Gene 103:171–177
Tjuvajev J, Gansbacher B, Desai R, Beattie B, Kaplitt M, Matei C, Koutcher J, Gilboa E, Blasberg R (1995a) RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma. Cancer Res 55:1902–1910
Tjuvajev JG, Stockhammer G, Desai R, Uehara H, Watanabe K, Gansbacher B, Blasberg RG (1995b) Imaging the expression of transfected genes in vivo. Cancer Res 55:6126–6132
Tjuvajev JG, Finn R, Watanabe K, Joshi R, Oku T, Kennedy J, Beattie B, Koutcher J, Larson S, Blasberg RG (1996) Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy. Cancer Res 56:4087–4095
Tjuvajev JG, Avril N, Oku T, Sasajima T, Miyagawa T, Joshi R, Safer M, Beattie B, DiResta G, Daghighian F, Augensen F, Koutcher J, Zweit J, Humm J, Larson SM, Finn R, Blasberg R (1998) Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. Cancer Res 58:4333–4341
Tjuvajev JG, Chen SH, Joshi A, Joshi R, Guo ZS, Balatoni J, Ballon D, Koutcher J, Finn R, Woo SL, Blasberg RG (1999) Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo. Cancer Res 59:5186–5193
Tjuvajev J, Blasberg R, Luo X, Zheng LM, King I, Bermudes D (2001) Salmonella-based tumor-targeted cancer therapy: tumor amplified protein expression therapy (TAPET) for diagnostic imaging. J Control Release 74:313–315
Tjuvajev JG, Doubrovin M, Akhurst T, Cai S, Balatoni J, Alauddin MM, Finn R, Bornmann W, Thaler H, Conti PS, Blasberg RG (2002) Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression. J Nucl Med 43:1072–1083
Tomita S, Mickle DA, Weisel RD, Jia ZQ, Tumiati LC, Allidina Y, Liu P, Li RK (2002) Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg 123:1132–1140
Tuveson DA, Willis NA, Jacks T, Griffin JD, Singer S, Fletcher CD, Fletcher JA, Demetri GD (2001) STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 20:5054–5058
Uhrbom L, Nerio E, Holland EC (2004) Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nat Med 10:1257–1260
van den Abbeele A (2001) F18-FDG-PET provides early evidence of biological response to ST1571 pateins with malignant gastointestinal stromal tumors (GIST). Proc Am Soc Clin Oncol 20:362a
Vose JM, Bierman PJ, Anderson JR, Harrison KA, Dalrymple GV, Byar K, Kessinger A, Armitage JO (1996) Single-photon emission computed tomography gallium imaging versus computed tomography: predictive value in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin’s lymphoma. J Clin Oncol 14:2473–2479
Wang GL, Semenza GL (1995) Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270:1230–1237
Wang L, Jackson WC, Steinbach PA, Tsien RY (2004) Evolution of new nonantibody proteins via iterative somatic hypermutation. Proc Natl Acad Sci USA 101:16745–16749
Wang X, Rosol M, Ge S, Peterson D, McNamara G, Pollack H, Kohn DB, Nelson MD, Crooks GM (2003) Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging. Blood 102:3478–3482
Wang Y, Iyer M, Annala A, Wu L, Carey M, Gambhir SS (2006) Noninvasive indirect imaging of vascular endothelial growth factor gene expression using bioluminescence imaging in living transgenic mice. Physiol Genomics 24:173–180
Warburg O (1956) On the origin of cancer cells. Science 123:309–314
Weber WA, Petersen V, Schmidt B, Tyndale-Hines L, Link T, Peschel C, Schwaiger M (2003) Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J Clin Oncol 21:2651–2657
Weissleder R (2002) Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2:11–18
Weissleder R, Ntziachristos V (2003) Shedding light onto live molecular targets. Nat Med 9: 123–128
Weissleder R, Simonova M, Bogdanova A, Bredow S, Enochs WS, Bogdanov A Jr (1997) MR imaging and scintigraphy of gene expression through melanin induction. Radiology 204: 425–429
Wilson T, Hastings JW (1998) Bioluminescence. Annu Rev Cell Dev Biol 14:197–230
Wong KK, Zou X, Merrell KT, Patel AJ, Marcu KB, Chellappan S, Calame K (1995) v-Abl activates c-myc transcription through the E2F site. Mol Cell Biol 15:6535–6544
Wu AM (2004) Engineering multivalent antibody fragments for in vivo targeting. Methods Mol Biol 248:209–225
Wu AM, Senter PD (2005) Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 23:1137–1146
Wu JC, Inubushi M, Sundaresan G, Schelbert HR, Gambhir SS (2002) Optical imaging of cardiac reporter gene expression in living rats. Circulation 105:1631–1634
Yaghoubi S, Barrio JR, Dahlbom M, Iyer M, Namavari M, Satyamurthy N, Goldman R, Herschman HR, Phelps ME, Gambhir SS (2001) Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. J Nucl Med 42:1225–1234
Yaghoubi SS, Barrio JR, Namavari M, Satyamurthy N, Phelps ME, Herschman HR, Gambhir SS (2005) Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography. Cancer Gene Ther 12:329–339
Yu YA, Timiryasova T, Zhang Q, Beltz R, Szalay AA (2003) Optical imaging: bacteria, viruses, and mammalian cells encoding light-emitting proteins reveal the locations of primary tumors and metastases in animals. Anal Bioanal Chem 377:964–972
Zhang L, Adams JY, Billick E, Ilagan R, Iyer M, Le K, Smallwood A, Gambhir SS, Carey M, Wu L (2002) Molecular engineering of a two-step transcription amplification (TSTA) system for transgene delivery in prostate cancer. Mol Ther 5:223–232
Zhang W FJ, Harris SE, Contag PR, Stevenson DK, Contag CH (2001) Rapid in vivo functional analysis of transgenes in mice using whole body imaging of luciferase expression. Transgenic Res 10:423-434
Zhu ZB, Makhija SK, Lu B, Wang M, Kaliberova L, Liu B, Rivera AA, Nettelbeck DM, Mahasreshti PJ, Leath CA, 3rd, Yamamoto M, Alvarez RD, Curiel DT (2004) Transcriptional targeting of adenoviral vector through the CXCR4 tumor-specific promoter. Gene Ther 11: 645–648
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Serganova, I., Mayer-Kukuck, P., Huang, R., Blasberg, R. (2008). Molecular Imaging: Reporter Gene Imaging. In: Semmler, W., Schwaiger, M. (eds) Molecular Imaging II. Handbook of Experimental Pharmacology, vol 185/2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-77496-9_8
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