Molecular Imaging of Cancer and the Implications for Pre-invasive Disease

  • Scott K. Lyons
  • Kevin M. BrindleEmail author


The fluorescence microscope is a standard tool in any cell biology lab, enabling the visualisation of appropriately labelled probe molecules in the context of cell anatomy. These probe molecules can be used to image various aspects of cell physiology and biochemistry, for example, the levels of intracellular Ca2+, the location, binding and mobility of specific proteins and, using gene reporter constructs, the transcriptional activity of specific genes. The techniques of molecular imaging allow similar measurements to be made deep inside the tissues of a living organism, for example in tumours in mouse models of cancer. Since many of the molecular imaging modalities that are employed in the laboratory can also be used clinically, the techniques of molecular imaging, in principle, also permit investigation of these fundamental aspects of tumour biology in the clinic. These techniques are set to play a key role in translational research, that is in translating our growing understanding of the cell biology of cancer and pre-invasive disease into new ways of detecting and treating the disease.


Positron Emission Tomography Single Photon Emission Compute Tomography Positron Emission Tomography Imaging Molecular Imaging Single Photon Emission Compute Tomography 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.


  1. 1.
    Eisenhauer E, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMedCrossRefGoogle Scholar
  2. 2.
    Weissleder R (1999) Molecular imaging: exploring the next frontier. Radiology 212:609–614PubMedGoogle Scholar
  3. 3.
    Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333PubMedGoogle Scholar
  4. 4.
    Weissleder R, Pittet M (2008) Imaging in the era of molecular oncology. Nature 452:580–589PubMedCrossRefGoogle Scholar
  5. 5.
    Gambhir SS (2002) Molecular imaging of cancer with positron emisson tomography. Nat Rev Cancer 2:683–693PubMedCrossRefGoogle Scholar
  6. 6.
    Margolis D, Hoffman J, Herfkens R, Jeffrey R, Quon A, Gambhir S (2007) Molecular imaging techniques in body imaging. Radiology 245:333–356PubMedCrossRefGoogle Scholar
  7. 7.
    Sullivan D, Kelloff G (2005) Seeing into cells – The promise of in vivo molecular imaging in oncology. EMBO Rep 6:292–296PubMedCrossRefGoogle Scholar
  8. 8.
    Weber W (2005) Use of PET for monitoring cancer therapy and for predicting outcome. J Nucl Med 46:983–995PubMedGoogle Scholar
  9. 9.
    Czernin J, Weber WA, Herschman HR (2006) Molecular imaging in the development of cancer therapeutics. Annu Rev Med 57:99–118PubMedCrossRefGoogle Scholar
  10. 10.
    Weber WA (2006) Positron emission tomography as an imaging biomarker. J Clin Oncol 24:3282–3292PubMedCrossRefGoogle Scholar
  11. 11.
    Neves AA, Brindle KM (2006) Assessing responses to cancer therapy using molecular imaging. Biochim Biophys Acta 1766:242–261PubMedGoogle Scholar
  12. 12.
    Brindle K (2008) New approaches for imaging tumour responses to treatment. Nat Rev Cancer 8:1–14CrossRefGoogle Scholar
  13. 13.
    Juweid M, Cheson B (2006) Positron-emission tomography and assessment of cancer therapy. N Engl J Med 354:496–507PubMedCrossRefGoogle Scholar
  14. 14.
    Weissleder R (2001) Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2:1–8Google Scholar
  15. 15.
    Frese KK, Tuveson DA (2007) Maximizing mouse cancer models. Nat Rev Cancer 7:654–658CrossRefGoogle Scholar
  16. 16.
    Testoni PA, Mangiavillano B (2008) Optical coherence tomography in detection of dysplasia and cancer of the gastrointestinal tract and bilio-pancreatic ductal system. World J Gastroenterol 14:6444–6452PubMedCrossRefGoogle Scholar
  17. 17.
    Kara MA, Bergman JJ (2006) Autofluorescence imaging and narrow-band imaging for the detection of early neoplasia in patients with Barrett’s esophagus. Endoscopy 38:627–631PubMedCrossRefGoogle Scholar
  18. 18.
    Moghissi K, Dixon K, Stringer MR (2008) Current indications and future perspective of fluorescence bronchoscopy: a review study. Photodiagnosis Photodyn Ther 5:238–246PubMedCrossRefGoogle Scholar
  19. 19.
    Hsiung PL, Hardy J, Friedland S et al (2008) Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy. Nat Med 14:454–458PubMedCrossRefGoogle Scholar
  20. 20.
    Kurhanewicz J, Swanson MG, Nelson SJ, Vigneron DB (2002) Combined magnetic resonance imaging and spectroscopic imaging approach to molecular imaging of prostate cancer. J Magn Reson Imaging 16:451–463PubMedCrossRefGoogle Scholar
  21. 21.
    Sawyers C (2008) The cancer biomarker problem. Nature 452:548–552PubMedCrossRefGoogle Scholar
  22. 22.
    Hanash SM, Pitteri SJ, Faca VM (2008) Mining the plasma proteome for cancer biomarkers. Nature 452:571–579PubMedCrossRefGoogle Scholar
  23. 23.
    Jana S, Blaufox MD (2006) Nuclear medicine studies of the prostate, testes, and bladder. Semin Nucl Med 36:51–72PubMedCrossRefGoogle Scholar
  24. 24.
    Lauterbur PC (1973) Image formation by induced local interactions: examples employing nuclear magnetic resonance. Nature 242:190–191CrossRefGoogle Scholar
  25. 25.
    Hoult D, Busby S, Gadian D, Radda G, Richards R, Seeley P (1974) Observation of tissue metabolites using 31P nuclear magnetic resonance. Nature 252:285–287PubMedCrossRefGoogle Scholar
  26. 26.
    Gadian DG, Radda GK (1981) NMR studies of tissue metabolism. Ann Rev Biochem 50:69–83PubMedCrossRefGoogle Scholar
  27. 27.
    Negendank W (1992) Studies of human tumours by MRS: a review. NMR Biomed 5:303–324PubMedCrossRefGoogle Scholar
  28. 28.
    Glunde K, Jacobs MA, Bhujwalla ZM (2006) Choline metabolism in cancer: implications for diagnosis and therapy. Expert Rev Mol Diagn 6:821–829PubMedCrossRefGoogle Scholar
  29. 29.
    Gadian DG (1995) NMR and its applications to living systems, 2nd edn. Oxford University Press, OxfordGoogle Scholar
  30. 30.
    McRobbie DW, Moore EA, Graves MJ, Prince MR (2006) MRI from picture to proton, 2nd edn. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  31. 31.
    Wuthrich K (1986) NMR of Proteins and Nucleic Acids. Wiley-Interscience, New YorkGoogle Scholar
  32. 32.
    Lindon JC, Nicholson JK, Wilson ID (1996) Direct coupling of chromatographic separations to NMR spectroscopy. Prog Nucl Magn Reson Spectrosc 29:1–49CrossRefGoogle Scholar
  33. 33.
    Raichle ME (2001) Bold insights. Nature 412:128–130PubMedCrossRefGoogle Scholar
  34. 34.
    Logothetis NK (2008) What we can do and what we cannot do with fMRI. Nature 453:869–878PubMedCrossRefGoogle Scholar
  35. 35.
    Robinson SP, Howe FA, Griffiths JR (1995) Noninvasive monitoring of carbogen-induced changes in tumor blood-flow and oxygenation by functional magnetic-resonance-imaging. Int J Radiat Oncol Biol Phys 33:855–859PubMedCrossRefGoogle Scholar
  36. 36.
    van Zijl PCM, Moonen CTW, Faustino P, Pekar J, Kaplan O, Cohen JS (1991) Complete separation of intracellular and extracellular information in NMR spectra of perfused cells by diffusion-weighted spectroscopy. Proc Natl Acad Sci USA 88:3228–3232PubMedCrossRefGoogle Scholar
  37. 37.
    Zhao M, Pipe JG, Bonnett J, Evelhoch JL (1996) Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy in a murine tumour in vivo. Br J Cancer 73:61–64PubMedCrossRefGoogle Scholar
  38. 38.
    Chenevert TL, Stegman LD, Taylor JMG et al (2000) Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. J Natl Cancer Inst 92:2029–2036PubMedCrossRefGoogle Scholar
  39. 39.
    Moffat BA, Chenevert TL, Lawrence TS et al (2005) Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. Proc Natl Acad Sci USA 102:5524–5529PubMedCrossRefGoogle Scholar
  40. 40.
    Aime S, Cabella C, Colombatto S, GeninattiCrich S, Gianollio E, Maggioni F (2002) Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations. J Magn Reson Imaging 16:394–406PubMedCrossRefGoogle Scholar
  41. 41.
    Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499PubMedCrossRefGoogle Scholar
  42. 42.
    Stuber M, Gilson WD, Schar M et al (2007) Positive contrast visualization of iron oxide-labeled stem cells using inversion-recovery with ON-Resonant water suppression (IRON). Magn Reson Med 58:1072–1077PubMedCrossRefGoogle Scholar
  43. 43.
    Wickline SA, Neubauer AM, Winter PM, Caruthers SD, Lanza GM (2007) Molecular imaging and therapy of atherosclerosis with targeted nanoparticles. J Magn Reson Imaging 25:667–680PubMedCrossRefGoogle Scholar
  44. 44.
    Shapiro EM, Skrtic S, Sharer K, Hill JM, Dunbar CE, Koretsky AP (2004) MRI detection of single particles for cellular imaging. Proc Natl Acad Sci USA 101:10901–10906PubMedCrossRefGoogle Scholar
  45. 45.
    de Vries I, Lesterhuis W, Barentsz J et al (2005) Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 23:1407–1413PubMedCrossRefGoogle Scholar
  46. 46.
    Leach MO, Brindle KM, Evelhoch JL et al (2005) The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations. Br J Cancer 92:1599–1610PubMedCrossRefGoogle Scholar
  47. 47.
    Brasch R, Pham C, Shames D et al (1997) Assessing tumor angiogenesis using macromolecular MR imaging contrast media. J Magn Reson Imaging 7:68–74PubMedCrossRefGoogle Scholar
  48. 48.
    Barrett T, Kobayashi H, Brechbiel M, Choyke PL (2006) Macromolecular MRI contrast agents for imaging tumor angiogenesis. Eur J Radiol 60:353–366PubMedCrossRefGoogle Scholar
  49. 49.
    McDonald DM, Choyke PL (2003) Imaging of angiogenesis: from microscope to clinic. Nat Med 9:713–725PubMedCrossRefGoogle Scholar
  50. 50.
    Hylton N (2006) Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. J Clin Oncol 24:3293–3298PubMedCrossRefGoogle Scholar
  51. 51.
    Tozer GM, Kanthou C, Baguley BC (2005) Disrupting tumour blood vessels. Nat Rev Cancer 5:423–435PubMedCrossRefGoogle Scholar
  52. 52.
    Miller JC, Pien HH, Sahani D, Sorensen AG, Thrall JH (2005) Imaging angiogenesis: applications and potential for drug development. J Natl Cancer Inst 97:172–187PubMedCrossRefGoogle Scholar
  53. 53.
    Morgan B, Thomas AL, Drevs J et al (2003) Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J Clin Oncol 21:3955–3964PubMedCrossRefGoogle Scholar
  54. 54.
    Stevenson JP, Rosen M, Sun WJ et al (2003) Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow. J Clin Oncol 21:4428–4438PubMedCrossRefGoogle Scholar
  55. 55.
    Aime S, Castelli D, Terreno E (2002) Novel pH-reporter MRI contrast agents. Angew Chem Int Ed 41:4334–4336CrossRefGoogle Scholar
  56. 56.
    Gillies RJ, Raghunand N, Garcia-Martin ML, Gatenby RA (2004) pH imaging. A review of pH measurement methods and applications in cancers. IEEE Eng Med Biol Mag 23:57–64PubMedCrossRefGoogle Scholar
  57. 57.
    Aime S, Fedeli F, Sanino A, Terreno E (2006) A R-2/R-1 ratiometric procedure for a concentration-independent, pH-responsive, Gd(III)-based MRI agent. J Am Chem Soc 128: 11326–11327PubMedCrossRefGoogle Scholar
  58. 58.
    Aime S, Barge A, Castelli DD et al (2002) Paramagnetic lanthanide(III) complexes as pH-sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications. Magn Reson Med 47:639–648PubMedCrossRefGoogle Scholar
  59. 59.
    Artemov D, Mori N, Ravi R, Bhujwalla ZM (2003) Magnetic resonance molecular imaging of the HER-2/neu receptor. Cancer Res 63:2723–2727PubMedGoogle Scholar
  60. 60.
    Artemov D, Mori N, Okollie B, Bhujwalla ZM (2003) MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles. Magn Reson Med 49:403–408PubMedCrossRefGoogle Scholar
  61. 61.
    Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KCP (1998) Detection of tumour angiogenesis in vivo by αvβ3-targeted magnetic resonance imaging. Nat Med 4:623–626PubMedCrossRefGoogle Scholar
  62. 62.
    Winter PM, Caruthers SD, Kassner A et al (2003) Molecular Imaging of angiogenesis in nascent vx-2 rabbit tumors using a novel alpha(v)beta(3)-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res 63:5838–5843PubMedGoogle Scholar
  63. 63.
    Zhao M, Beauregard DA, Loizou L, Davletov B, Brindle KM (2001) Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nat Med 7:1241–1244PubMedCrossRefGoogle Scholar
  64. 64.
    van Tilborg GAF, Mulder WJM, Deckers N et al (2006) Annexin A5-functionalized bimodal lipid-based contrast agents for the detection of apoptosis. Bioconjug Chem 17:741–749PubMedCrossRefGoogle Scholar
  65. 65.
    Krishnan AS, Neves AA, de Backer MM et al (2008) Detection of cell death in tumors using MRI and a gadolinium-based targeted contrast agent. Radiology 246:854–862PubMedCrossRefGoogle Scholar
  66. 66.
    Lauenstein T, Salman K, Morreira R et al (2007) Nephrogenic systemic fibrosis: center case review. J Magn Reson Imaging 26:1198–1203PubMedCrossRefGoogle Scholar
  67. 67.
    Podo F, Sardanelli F, Iorio E et al (2007) Abnormal choline phospholipid metabolism in breast and ovary cancer: molecular bases for noninvasive imaging approaches. Curr Med Imaging Rev 3:123–137CrossRefGoogle Scholar
  68. 68.
    Hu JN, Feng WZ, Hua J et al (2009) A high spatial resolution in vivo 1H magnetic resonance spectroscopic imaging technique for the human breast at 3 T. Med Phys 36:4870–4877PubMedCrossRefGoogle Scholar
  69. 69.
    Kurhanewicz J, Vigneron DB, Nelson SJ (2000) Three-dimensional magnetic resonance spectroscopic imaging of brain and prostate cancer. Neoplasia 2:166–189PubMedCrossRefGoogle Scholar
  70. 70.
    Meisamy S, Bolan PJ, Baker EH et al (2004) Neoadjuvant chemotherapy of locally advanced breast cancer: predicting response with in vivo H-1 MR spectroscopy - A pilot study. Radiology 233:424–431PubMedCrossRefGoogle Scholar
  71. 71.
    Kumar R, Kumar M, Jagannathan NR, Gupta NP, Hemal AK (2004) Proton magnetic resonance spectroscopy with a body coil in the diagnosis of carcinoma prostate. Urol Res 32:36–40PubMedCrossRefGoogle Scholar
  72. 72.
    Mueller-Lisse UG, Scherr MK (2007) Proton MR spectroscopy of the prostate. Eur J Radiol 63:351–360PubMedCrossRefGoogle Scholar
  73. 73.
    Futterer JJ, Heijmink S, Scheenen TWJ et al (2006) Prostate cancer localization with dynamic contrast-enhanced MR imaging and proton MR spectroscopic imaging. Radiology 241:449–458PubMedCrossRefGoogle Scholar
  74. 74.
    Magalhaes A, Godfrey W, Shen YM, Hu JN, Smith W (2005) Proton magnetic resonance spectroscopy of brain tumors correlated with pathology. Acad Radiol 12:51–57PubMedCrossRefGoogle Scholar
  75. 75.
    Chen J, Huang SL, Li T, Chen XL (2006) In vivo research in astrocytoma cell proliferation with H-1-magnetic resonance spectroscopy: correlation with histopathology and immunohistochemistry. Neuroradiology 48:312–318PubMedCrossRefGoogle Scholar
  76. 76.
    Spampinato MV, Smith JK, Kwock L et al (2007) Cerebral blood volume measurements and proton MR spectroscopy in grading of oligodendroglial tumors. AJR Am J Roentgenol 188:204–212PubMedCrossRefGoogle Scholar
  77. 77.
    Chernov MF, Nakaya K, Kasuya H et al (2009) Metabolic alterations in the peritumoral brain in cases of meningiomas: H-1-MRS study. J Neurol Sci 284:168–174PubMedCrossRefGoogle Scholar
  78. 78.
    Hazany S, Hesselink JR, Healy JF, Imbesi SG (2007) Utilization of glutamate/creatine ratios for proton spectroscopic diagnosis of meningiomas. Neuroradiology 49:121–127PubMedCrossRefGoogle Scholar
  79. 79.
    Tate A, Underwood J, Acosta D et al (2006) Development of a decision support system for diagnosis and grading of brain tumours using in vivo magnetic resonance single voxel spectra. NMR Biomed 19:411–434PubMedCrossRefGoogle Scholar
  80. 80.
    Roden M, Shulman GI (1999) Applications of NMR spectroscopy to study muscle glycogen metabolism in man. Annu Rev Med 50:277–290PubMedCrossRefGoogle Scholar
  81. 81.
    Ardenkjaer-Larsen JH, Fridlund B, Gram A et al (2003) Increase in signal-to-noise ratio of >10, 000 times in liquid-state NMR. Proc Natl Acad Sci USA 100:10158–10163PubMedCrossRefGoogle Scholar
  82. 82.
    Gallagher F, Kettunen M, Brindle K (2009) Biomedical applications of hyperpolarized 13C magnetic resonance imaging. Prog NMR Spec 55:285–295CrossRefGoogle Scholar
  83. 83.
    Golman K, Petersson JS, Magnusson P et al (2008) Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med 59:1005–1013PubMedCrossRefGoogle Scholar
  84. 84.
    Day SE, Kettunen MI, Gallagher FA et al (2007) Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med 13:1382–1387PubMedCrossRefGoogle Scholar
  85. 85.
    Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899PubMedCrossRefGoogle Scholar
  86. 86.
    Albers M, Bok R, Chen A et al (2008) Hyperpolarized C-13 lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Cancer Res 68:8607–8615PubMedCrossRefGoogle Scholar
  87. 87.
    Gallagher FA, Kettunen MI, Hu DE et al (2009) Production of hyperpolarized [1, 4-C-13(2)]malate from [1, 4-C-13(2)]fumarate is a marker of cell necrosis and treatment response in tumors. Proc Natl Acad Sci USA 106:19801–19806PubMedGoogle Scholar
  88. 88.
    Gallagher F, Kettunen M, Day S, Lerche M, Brindle K (2008) 13C Magnetic resonance spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C-labeled glutamine. Magn Reson Med 60:253–257PubMedCrossRefGoogle Scholar
  89. 89.
    Gallagher F, Kettunen M, Day S et al (2008) Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labeled bicarbonate. Nature 453:940–943PubMedCrossRefGoogle Scholar
  90. 90.
    Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17:545–580PubMedCrossRefGoogle Scholar
  91. 91.
    Robbins E (2008) Radiation risks from imaging studies in children with cancer. Pediatr Blood Cancer 51:453–457PubMedCrossRefGoogle Scholar
  92. 92.
    Carney JP, Townsend DW, Rappoport V, Bendriem B (2006) Method for transforming CT images for attenuation correction in PET/CT imaging. Med Phys 33:976–983PubMedCrossRefGoogle Scholar
  93. 93.
    Moses WW (2007) Recent advances and future advances in time-of-flight PET. Nucl Instrum Methods Phys Res A 580:919–924PubMedCrossRefGoogle Scholar
  94. 94.
    Ullrich RT, Kracht L, Brunn A et al (2009) Methyl-L-11C-methionine PET as a diagnostic marker for malignant progression in patients with glioma. J Nucl Med 50:1962–1968PubMedCrossRefGoogle Scholar
  95. 95.
    Soloviev D, Fini A, Chierichetti F, Al-Nahhas A, Rubello D (2008) PET imaging with 11C-acetate in prostate cancer: a biochemical, radiochemical and clinical perspective. Eur J Nucl Med Mol Imaging 35:942–949PubMedCrossRefGoogle Scholar
  96. 96.
    Di Bartolo N, Sargeson AM, Smith SV (2006) New 64Cu PET imaging agents for personalised medicine and drug development using the hexa-aza cage, SarAr. Org Biomol Chem 4:3350–3357PubMedCrossRefGoogle Scholar
  97. 97.
    Voss SD, Smith SV, DiBartolo N et al (2007) Positron emission tomography (PET) imaging of neuroblastoma and melanoma with 64Cu-SarAr immunoconjugates. Proc Natl Acad Sci USA 104:17489–17493PubMedCrossRefGoogle Scholar
  98. 98.
    Emonds KM, Swinnen JV, Mortelmans L, Mottaghy FM (2009) Molecular imaging of prostate cancer. Methods 48:193–199PubMedCrossRefGoogle Scholar
  99. 99.
    Beer AJ, Haubner R, Sarbia M et al (2006) Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 12:3942–3949PubMedCrossRefGoogle Scholar
  100. 100.
    Beer AJ, Lorenzen S, Metz S et al (2008) Comparison of integrin alphaVbeta3 expression and glucose metabolism in primary and metastatic lesions in cancer patients: a PET study using 18F-galacto-RGD and 18F-FDG. J Nucl Med 49:22–29PubMedCrossRefGoogle Scholar
  101. 101.
    Mortimer JE, Dehdashti F, Siegel BA, Katzenellenbogen JA, Fracasso P, Welch MJ (1996) Positron emission tomography with 2-[18F]Fluoro-2-deoxy-D-glucose and 16alpha-[18F]fluoro-17beta-estradiol in breast cancer: correlation with estrogen receptor status and response to systemic therapy. Clin Cancer Res 2:933–939PubMedGoogle Scholar
  102. 102.
    Peterson LM, Mankoff DA, Lawton T et al (2008) Quantitative imaging of estrogen receptor expression in breast cancer with PET and 18F-fluoroestradiol. J Nucl Med 49: 367–374PubMedCrossRefGoogle Scholar
  103. 103.
    Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ (2001) Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 19:2797–2803PubMedGoogle Scholar
  104. 104.
    Shah C, Miller TW, Wyatt SK et al (2009) Imaging biomarkers predict response to anti-HER2 (ErbB2) therapy in preclinical models of breast cancer. Clin Cancer Res 15: 4712–4721PubMedCrossRefGoogle Scholar
  105. 105.
    Cohen A, Shirvan A, Levin G, Grimberg H, Reshef A, Ziv I (2009) From the Gla domain to a novel small-molecule detector of apoptosis. Cell Res 19:625–637PubMedCrossRefGoogle Scholar
  106. 106.
    Nguyen QD, Smith G, Glaser M, Perumal M, Arstad E, Aboagye EO (2009) Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-3/7 specific [18F]-labeled isatin sulfonamide. Proc Natl Acad Sci USA 106:16375–16380PubMedCrossRefGoogle Scholar
  107. 107.
    Eschmann SM, Paulsen F, Reimold M et al (2005) Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 46:253–260PubMedGoogle Scholar
  108. 108.
    Spence AM, Muzi M, Swanson KR et al (2008) Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res 14:2623–2630PubMedCrossRefGoogle Scholar
  109. 109.
    Lee N, Nehmeh S, Schoder H et al (2009) Prospective trial incorporating pre-/mid-treatment [18F]-misonidazole positron emission tomography for head-and-neck cancer patients undergoing concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys 75:101–108PubMedCrossRefGoogle Scholar
  110. 110.
    Lehmann S, Stiehl DP, Honer M et al (2009) Longitudinal and multimodal in vivo imaging of tumor hypoxia and its downstream molecular events. Proc Natl Acad Sci USA 106:14004–14009PubMedCrossRefGoogle Scholar
  111. 111.
    Buchmann I, Henze M, Engelbrecht S et al (2007) Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 34:1617–1626PubMedCrossRefGoogle Scholar
  112. 112.
    Miyagawa T, Gogiberidze G, Serganova I et al (2008) Imaging of HSV-tk Reporter gene expression: comparison between [18F]FEAU, [18F]FFEAU, and other imaging probes. J Nucl Med 49:637–648PubMedCrossRefGoogle Scholar
  113. 113.
    Kang KW, Min JJ, Chen X, Gambhir SS (2005) Comparison of [14C]FMAU, [3H]FEAU, [14C]FIAU, and [3H]PCV for monitoring reporter gene expression of wild type and mutant herpes simplex virus type 1 thymidine kinase in cell culture. Mol Imaging Biol 7:296–303PubMedCrossRefGoogle Scholar
  114. 114.
    Yaghoubi SS, Gambhir SS (2006) PET imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk reporter gene expression in mice and humans using [18F]FHBG. Nat Protoc 1:3069–3075PubMedCrossRefGoogle Scholar
  115. 115.
    Deng WP, Wu CC, Lee CC et al (2006) Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir. J Nucl Med 47:877–884PubMedGoogle Scholar
  116. 116.
    Maatta AM, Samaranayake H, Pikkarainen J, Wirth T, Yla-Herttuala S (2009) Adenovirus mediated herpes simplex virus-thymidine kinase/ganciclovir gene therapy for resectable malignant glioma. Curr Gene Ther 9:356–367PubMedCrossRefGoogle Scholar
  117. 117.
    Gambhir SS, Bauer E, Black ME et al (2000) 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 97:2785–2790PubMedCrossRefGoogle Scholar
  118. 118.
    Dingli D, Kemp BJ, O’Connor MK, Morris JC, Russell SJ, Lowe VJ (2006) Combined I-124 positron emission tomography/computed tomography imaging of NIS gene expression in animal models of stably transfected and intravenously transfected tumor. Mol Imaging Biol 8:16–23PubMedCrossRefGoogle Scholar
  119. 119.
    Che J, Doubrovin M, Serganova I, Ageyeva L, Zanzonico P, Blasberg R (2005) hNIS-IRES-eGFP dual reporter gene imaging. Mol Imaging 4:128–136PubMedGoogle Scholar
  120. 120.
    Niu G, Gaut AW, Ponto LL et al (2004) Multimodality noninvasive imaging of gene transfer using the human sodium iodide symporter. J Nucl Med 45:445–449PubMedGoogle Scholar
  121. 121.
    Scholz IV, Cengic N, Baker CH et al (2005) Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer. Gene Ther 12:272–280PubMedCrossRefGoogle Scholar
  122. 122.
    Park SY, Kwak W, Thapa N et al (2008) Combination therapy and noninvasive imaging with a dual therapeutic vector expressing MDR1 short hairpin RNA and a sodium iodide symporter. J Nucl Med 49:1480–1488PubMedCrossRefGoogle Scholar
  123. 123.
    Kim YJ, Dubey P, Ray P, Gambhir SS, Witte ON (2004) Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene. Mol Imaging Biol 6:331–340PubMedCrossRefGoogle Scholar
  124. 124.
    Penuelas I, Haberkorn U, Yaghoubi S, Gambhir SS (2005) Gene therapy imaging in patients for oncological applications. Eur J Nucl Med Mol Imaging 32(Suppl 2):S384–S403PubMedCrossRefGoogle Scholar
  125. 125.
    Dubey P, Su H, Adonai N et al (2003) Quantitative imaging of the T cell antitumor response by positron-emission tomography. Proc Natl Acad Sci USA 100:1232–1237PubMedCrossRefGoogle Scholar
  126. 126.
    Koehne G, Doubrovin M, Doubrovina E et al (2003) Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes. Nat Biotechnol 21:405–413PubMedCrossRefGoogle Scholar
  127. 127.
    Doubrovin M, Ponomarev V, Beresten T et al (2001) Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci USA 98:9300–9305PubMedCrossRefGoogle Scholar
  128. 128.
    Serganova I, Doubrovin M, Vider J et al (2004) Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. Cancer Res 64:6101–6108PubMedCrossRefGoogle Scholar
  129. 129.
    Che J, Doubrovin M, Serganova I et al (2007) HSP70-inducible hNIS-IRES-eGFP reporter imaging: response to heat shock. Mol Imaging 6:404–416PubMedGoogle Scholar
  130. 130.
    Catana C, Procissi D, Wu Y et al (2008) Simultaneous in vivo positron emission tomography and magnetic resonance imaging. Proc Natl Acad Sci USA 105:3705–3710PubMedCrossRefGoogle Scholar
  131. 131.
    Schlemmer HP, Pichler BJ, Schmand M et al (2008) Simultaneous MR/PET imaging of the human brain: feasibility study. Radiology 248:1028–1035PubMedCrossRefGoogle Scholar
  132. 132.
    Hofmann M, Steinke F, Scheel V et al (2008) MRI-based attenuation correction for PET/MRI: a novel approach combining pattern recognition and atlas registration. J Nucl Med 49:1875–1883PubMedCrossRefGoogle Scholar
  133. 133.
    Martinez-Moller A, Souvatzoglou M, Delso G et al (2009) Tissue classification as a potential approach for attenuation correction in whole-body PET/MRI: evaluation with PET/CT data. J Nucl Med 50:520–526PubMedCrossRefGoogle Scholar
  134. 134.
    Beekman F, van der Have F (2007) The pinhole: gateway to ultra-high-resolution three-dimensional radionuclide imaging. Eur J Nucl Med Mol Imaging 34:151–161PubMedCrossRefGoogle Scholar
  135. 135.
    Sosabowski JK, Mather SJ (2006) Conjugation of DOTA-like chelating agents to peptides and radiolabeling with trivalent metallic isotopes. Nat Protoc 1:972–976PubMedCrossRefGoogle Scholar
  136. 136.
    Tomura N, Watanabe O, Takahashi S et al (2006) Comparison of 201Tl-chloride SPECT with 99mtc-MIBI SPECT in the depiction of malignant head and neck tumors. Ann Nucl Med 20:107–114PubMedCrossRefGoogle Scholar
  137. 137.
    Nishiyama Y, Yamamoto Y, Yokoe K et al (2004) Superimposed dual-isotope SPECT using 99mTc-hydroxymethylene diphosphonate and 201Tl-chloride to assess cartilage invasion in laryngohypopharyngeal cancer. Ann Nucl Med 18:527–532PubMedCrossRefGoogle Scholar
  138. 138.
    Suzuki A, Togawa T, Kuyama J et al (2004) Evaluation of mandibular invasion by head and neck cancers using 99mTc-methylene diphosphonate or 99mTc-hydroxymethylene diphosphonate and 201Tl chloride dual isotope single photon emission computed tomography. Ann Nucl Med 18:399–408PubMedCrossRefGoogle Scholar
  139. 139.
    van de Wiele C, Lahorte C, Vermeersch H et al (2003) Quantitative tumor apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography. J Clin Oncol 21:3483–3487PubMedCrossRefGoogle Scholar
  140. 140.
    Kartachova M, van Zandwijk N, Burgers S, van Tinteren H, Verheij M, Valdes Olmos RA (2007) Prognostic significance of 99mTc Hynic-rh-annexin V scintigraphy during platinum-based chemotherapy in advanced lung cancer. J Clin Oncol 25:2534–2539PubMedCrossRefGoogle Scholar
  141. 141.
    Balon HR, Goldsmith SJ, Siegel BA et al (2001) Procedure guideline for somatostatin receptor scintigraphy with (111)In-pentetreotide. J Nucl Med 42:1134–1138PubMedGoogle Scholar
  142. 142.
    Perri M, Erba P, Volterrani D et al (2008) Octreo-SPECT/CT imaging for accurate detection and localization of suspected neuroendocrine tumors. Q J Nucl Med Mol Imaging 52:323–333PubMedGoogle Scholar
  143. 143.
    Akgun A, Cok G, Karapolat I, Goksel T, Burak Z (2006) Tc-99m MIBI SPECT in prediction of prognosis in patients with small cell lung cancer. Ann Nucl Med 20:269–275PubMedCrossRefGoogle Scholar
  144. 144.
    Saggiorato E, Angusti T, Rosas R et al (2009) 99mTc-MIBI Imaging in the presurgical characterization of thyroid follicular neoplasms: relationship to multidrug resistance protein expression. J Nucl Med 50:1785–1793PubMedCrossRefGoogle Scholar
  145. 145.
    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 22:1567–1572PubMedCrossRefGoogle Scholar
  146. 146.
    Troyan SL, Kianzad V, Gibbs-Strauss SL et al (2009) The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping. Ann Surg Oncol 16:2943–2952PubMedCrossRefGoogle Scholar
  147. 147.
    Winer JH, Choi HS, Gibbs-Strauss SL, Ashitate Y, Colson YL, Frangioni JV (2010) Intraoperative localization of insulinoma and normal pancreas using invisible near-infrared fluorescent light. Ann Surg Oncol 17:1094–1100PubMedCrossRefGoogle Scholar
  148. 148.
    Rao J, Dragulescu-Andrasi A, Yao H (2007) Fluorescence imaging in vivo: recent advances. Curr Opin Biotechnol 18:17–25PubMedCrossRefGoogle Scholar
  149. 149.
    Lyons SK, Lim E, Clermont AO et al (2006) Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice. Cancer Res 66:4701–4707PubMedCrossRefGoogle Scholar
  150. 150.
    Fan F, Wood KV (2007) Bioluminescent assays for high-throughput screening. Assay Drug Dev Technol 5:127–136PubMedCrossRefGoogle Scholar
  151. 151.
    Tannous BA, Kim DE, Fernandez JL, Weissleder R, Breakefield XO (2005) Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol Ther 11:435–443PubMedCrossRefGoogle Scholar
  152. 152.
    Loening AM, Wu AM, Gambhir SS (2007) Red-shifted Renilla reniformis luciferase variants for imaging in living subjects. Nat Meth 4:641–643CrossRefGoogle Scholar
  153. 153.
    Loening AM, Dragulescu-Andrasi A, Gambhir SS (2010) A red-shifted Renilla luciferase for transient reporter-gene expression. Nat Meth 7:5–6CrossRefGoogle Scholar
  154. 154.
    Rabinovich BA, Ye Y, Etto T et al (2008) Visualizing fewer than 10 mouse T cells with an enhanced firefly luciferase in immunocompetent mouse models of cancer. Proc Natl Acad Sci U S A 105:14342–14346PubMedCrossRefGoogle Scholar
  155. 155.
    Deroose CM, De A, Loening AM et al (2007) Multimodality imaging of tumor xenografts and metastases in mice with combined small-animal PET, small-animal CT, and bioluminescence imaging. J Nucl Med 48:295–303PubMedGoogle Scholar
  156. 156.
    Kuo C, Coquoz O, Troy TL, Xu H, Rice BW (2007) Three-dimensional reconstruction of in vivo bioluminescent sources based on multispectral imaging. J Biomed Opt 12:024007PubMedCrossRefGoogle Scholar
  157. 157.
    Jenkins DE, Yu SF, Hornig YS, Purchio T, Contag PR (2003) In vivo monitoring of tumor relapse and metastasis using bioluminescent PC-3M-luc-C6 cells in murine models of human prostate cancer. Clin Exp Metastasis 20:745–756PubMedCrossRefGoogle Scholar
  158. 158.
    Edinger M, Cao YA, Verneris MR, Bachmann MH, Contag CH, Negrin RS (2003) Revealing lymphoma growth and the efficacy of immune cell therapies using in vivo bioluminescence imaging. Blood 101:640–648PubMedCrossRefGoogle Scholar
  159. 159.
    Zhang C, Yan Z, Arango ME, Painter CL, Anderes K (2009) Advancing bioluminescence imaging technology for the evaluation of anticancer agents in the MDA-MB-435-HAL-Luc mammary fat pad and subrenal capsule tumor models. Clin Cancer Res 15:238–246PubMedCrossRefGoogle Scholar
  160. 160.
    Vooijs M, Jonkers J, Lyons S, Berns A (2002) Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer Res 62:1862–1867PubMedGoogle Scholar
  161. 161.
    Zhang N, Lyons S, Lim E, Lassota P (2009) A spontaneous acinar cell carcinoma model for monitoring progression of pancreatic lesions and response to treatment through noninvasive bioluminescence imaging. Clin Cancer Res 15:4915–4924PubMedCrossRefGoogle Scholar
  162. 162.
    Uhrbom L, Nerio E, Holland EC (2004) Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nat Med 10:1257–1260PubMedCrossRefGoogle Scholar
  163. 163.
    Hamstra DA, Bhojani MS, Griffin LB, Laxman B, Ross BD, Rehemtulla A (2006) Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging. Cancer Res 66:7482–7489PubMedCrossRefGoogle Scholar
  164. 164.
    Laxman B, Hall DE, Bhojani MS et al (2002) Noninvasive real-time imaging of apoptosis. Proc Natl Acad Sci USA 99:16551–16555PubMedCrossRefGoogle Scholar
  165. 165.
    Lee KC, Hamstra DA, Bhojani MS, Khan AP, Ross BD, Rehemtulla A (2007) Noninvasive molecular imaging sheds light on the synergy between 5-fluorouracil and TRAIL/Apo2L for cancer therapy. Clin Cancer Res 13:1839–1846PubMedCrossRefGoogle Scholar
  166. 166.
    Zhang L, Lee KC, Bhojani MS et al (2007) Molecular imaging of Akt kinase activity. Nat Med 13:1114–1119PubMedCrossRefGoogle Scholar
  167. 167.
    Paulmurugan R, Gambhir SS (2003) Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation. Anal Chem 75: 1584–1589PubMedCrossRefGoogle Scholar
  168. 168.
    Luker GD, Sharma V, Pica CM et al (2002) Noninvasive imaging of protein-protein interactions in living animals. Proc Natl Acad Sci USA 99:6961–6966PubMedCrossRefGoogle Scholar
  169. 169.
    Luker KE, Gupta M, Luker GD (2009) Imaging chemokine receptor dimerization with firefly luciferase complementation. FASEB J 23:823–834PubMedCrossRefGoogle Scholar
  170. 170.
    Chan CT, Paulmurugan R, Gheysens OS, Kim J, Chiosis G, Gambhir SS (2008) Molecular imaging of the efficacy of heat shock protein 90 inhibitors in living subjects. Cancer Res 68:216–226PubMedCrossRefGoogle Scholar
  171. 171.
    Paulmurugan R, Gambhir SS (2006) An intramolecular folding sensor for imaging estrogen receptor-ligand interactions. Proc Natl Acad Sci USA 103:15883–15888PubMedCrossRefGoogle Scholar
  172. 172.
    Inoue Y, Izawa K, Kiryu S, Tojo A, Ohtomo K (2008) Diet and abdominal autofluorescence detected by in vivo fluorescence imaging of living mice. Mol Imaging 7:21–27PubMedGoogle Scholar
  173. 173.
    Xu H, Rice BW (2009) In-vivo fluorescence imaging with a multivariate curve resolution spectral unmixing technique. J Biomed Opt 14:064011PubMedCrossRefGoogle Scholar
  174. 174.
    Niedre MJ, de Kleine RH, Aikawa E, Kirsch DG, Weissleder R, Ntziachristos V (2008) Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo. Proc Natl Acad Sci USA 105:19126–19131PubMedCrossRefGoogle Scholar
  175. 175.
    Mayinger B, Neumann F, Kastner C, Haider T, Schwab D (2010) Hexaminolevulinate-induced fluorescence colonoscopy versus white light endoscopy for diagnosis of neoplastic lesions in the colon. Endoscopy 42:28–33PubMedCrossRefGoogle Scholar
  176. 176.
    Kimura T, Muguruma N, Ito S et al (2007) Infrared fluorescence endoscopy for the diagnosis of superficial gastric tumors. Gastrointest Endosc 66:37–43PubMedCrossRefGoogle Scholar
  177. 177.
    Upadhyay R, Sheth RA, Weissleder R, Mahmood U (2007) Quantitative real-time catheter-based fluorescence molecular imaging in mice. Radiology 245:523–531PubMedCrossRefGoogle Scholar
  178. 178.
    Zhong W, Celli JP, Rizvi I et al (2009) In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring. Br J Cancer 101:2015–2022PubMedCrossRefGoogle Scholar
  179. 179.
    Winkler F, Kozin SV, Tong RT et al (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563PubMedGoogle Scholar
  180. 180.
    Fukumura D, Jain RK (2008) Imaging angiogenesis and the microenvironment. APMIS 116:695–715PubMedCrossRefGoogle Scholar
  181. 181.
    Giampieri S, Manning C, Hooper S, Jones L, Hill CS, Sahai E (2009) Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility. Nat Cell Biol 11:1287–1296PubMedCrossRefGoogle Scholar
  182. 182.
    Kienast Y, von Baumgarten L, Fuhrmann M et al (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nat Med 16:116–122PubMedCrossRefGoogle Scholar
  183. 183.
    Helmchen F, Denk W (2005) Deep tissue two-photon microscopy. Nat Meth 2:932–940CrossRefGoogle Scholar
  184. 184.
    Citrin D, Lee AK, Scott T et al (2004) In vivo tumor imaging in mice with near-infrared labeled endostatin. Mol Cancer Ther 3:481–488PubMedGoogle Scholar
  185. 185.
    Montet X, Figueiredo JL, Alencar H, Ntziachristos V, Mahmood U, Weissleder R (2007) Tomographic fluorescence imaging of tumor vascular volume in mice. Radiology 242:751–758PubMedCrossRefGoogle Scholar
  186. 186.
    Ke S, Wen X, Gurfinkel M et al (2003) Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts. Cancer Res 63:7870–7875PubMedGoogle Scholar
  187. 187.
    Moore A, Medarova Z, Potthast A, Dai G (2004) In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe. Cancer Res 64:1821–1827PubMedCrossRefGoogle Scholar
  188. 188.
    Wu Y, Cai W, Chen X (2006) Near-infrared fluorescence imaging of tumor integrin alpha v beta 3 expression with Cy7-labeled RGD multimers. Mol Imaging Biol 8:226–236PubMedCrossRefGoogle Scholar
  189. 189.
    Mulder WJ, Castermans K, van Beijnum JR et al (2009) Molecular imaging of tumor angiogenesis using alphavbeta3-integrin targeted multimodal quantum dots. Angiogenesis 12:17–24PubMedCrossRefGoogle Scholar
  190. 190.
    Koyama Y, Hama Y, Urano Y, Nguyen DM, Choyke PL, Kobayashi H (2007) Spectral fluorescence molecular imaging of lung metastases targeting HER2/neu. Clin Cancer Res 13:2936–2945PubMedCrossRefGoogle Scholar
  191. 191.
    Edgington LE, Berger AB, Blum G et al (2009) Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes. Nat Med 15:967–973PubMedCrossRefGoogle Scholar
  192. 192.
    Blum G, Mullins SR, Keren K et al (2005) Dynamic imaging of protease activity with fluorescently quenched activity-based probes. Nat Chem Biol 1:203–209PubMedCrossRefGoogle Scholar
  193. 193.
    Blum G, von Degenfeld G, Merchant MJ, Blau HM, Bogyo M (2007) Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat Chem Biol 3:668–677PubMedCrossRefGoogle Scholar
  194. 194.
    Grimm J, Kirsch DG, Windsor SD et al (2005) Use of gene expression profiling to direct in vivo molecular imaging of lung cancer. Proc Natl Acad Sci USA 102:14404–14409PubMedCrossRefGoogle Scholar
  195. 195.
    McIntyre JO, Matrisian LM (2009) Optical proteolytic beacons for in vivo detection of matrix metalloproteinase activity. Meth Mol Biol 539:155–174CrossRefGoogle Scholar
  196. 196.
    Ogawa M, Kosaka N, Choyke PL, Kobayashi H (2009) In vivo molecular imaging of cancer with a quenching near-infrared fluorescent probe using conjugates of monoclonal antibodies and indocyanine green. Cancer Res 69:1268–1272PubMedCrossRefGoogle Scholar
  197. 197.
    Urano Y, Asanuma D, Hama Y et al (2009) Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat Med 15:104–109PubMedCrossRefGoogle Scholar
  198. 198.
    Katz MH, Takimoto S, Spivack D, Moossa AR, Hoffman RM, Bouvet M (2003) A novel red fluorescent protein orthotopic pancreatic cancer model for the preclinical evaluation of chemotherapeutics. J Surg Res 113:151–160PubMedCrossRefGoogle Scholar
  199. 199.
    Yang M, Li L, Jiang P, Moossa AR, Penman S, Hoffman RM (2003) Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells. Proc Natl Acad Sci USA 100:14259–14262PubMedCrossRefGoogle Scholar
  200. 200.
    Amoh Y, Katsuoka K, Hoffman RM (2008) Color-coded fluorescent protein imaging of angiogenesis: the AngioMouse models. Curr Pharm Des 14:3810–3819PubMedCrossRefGoogle Scholar
  201. 201.
    Sakaue-Sawano A, Kurokawa H, Morimura T et al (2008) Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132:487–498PubMedCrossRefGoogle Scholar
  202. 202.
    Mocanu JD, Moriyama EH, Chia MC et al (2004) Combined in vivo bioluminescence and fluorescence imaging for cancer gene therapy. Mol Imaging 3:352–355PubMedCrossRefGoogle Scholar
  203. 203.
    Kimball KJ, Rivera AA, Zinn KR et al (2009) Novel infectivity-enhanced oncolytic adenovirus with a capsid-incorporated dual-imaging moiety for monitoring virotherapy in ovarian cancer. Mol Imaging 8:264–277PubMedGoogle Scholar
  204. 204.
    Kesarwala AH, Prior JL, Sun J, Harpstrite SE, Sharma V, Piwnica-Worms D (2006) Second-generation triple reporter for bioluminescence, micro-positron emission tomography, and fluorescence imaging. Mol Imaging 5:465–474PubMedGoogle Scholar
  205. 205.
    Ray P, Tsien R, Gambhir SS (2007) Construction and validation of improved triple fusion reporter gene vectors for molecular imaging of living subjects. Cancer Res 67:3085–3093PubMedCrossRefGoogle Scholar
  206. 206.
    Shu X, Royant A, Lin MZ et al (2009) Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome. Science 324:804–807PubMedCrossRefGoogle Scholar
  207. 207.
    Vakoc BJ, Lanning RM, Tyrrell JA et al (2009) Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nat Med 15: 1219–1223PubMedCrossRefGoogle Scholar
  208. 208.
    De la Zerda A, Zavaleta C, Keren S et al (2008) Carbon nanotubes as photoacoustic molecular imaging agents in living mice. Nat Nanotechnol 3:557–562PubMedCrossRefGoogle Scholar
  209. 209.
    Razansky D, Baeten J, Ntziachristos V (2009) Sensitivity of molecular target detection by multispectral optoacoustic tomography (MSOT). Med Phys 36:939–945PubMedCrossRefGoogle Scholar
  210. 210.
    Kim JW, Galanzha EI, Shashkov EV, Moon HM, Zharov VP (2009) Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents. Nat Nanotechnol 4:688–694PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Cancer Research UK, Cambridge Research Institute, Li Ka Shing CentreCambridgeUK
  2. 2.Department of BiochemistryUniversity of CambridgeCambridgeUK

Personalised recommendations