Skip to main content
SpringerLink
Log in

Applications of Small-Animal Molecular Imaging in Drug Development

  • Chapter
  • First Online:
Molecular Imaging of Small Animals

Abstract

The gauntlet for a new drug to succeed is a daunting one. The reduction in the time and cost required for modern drug discovery and development serves as a crucial need. An important element to accelerate drug discovery and development process is the rapid identification of promising drug candidates as opposed to the non-starters before unnecessary vast sums are invested. The aim of molecular imaging is to precisely visualize, characterize, and measure biological processes at the molecular and cellular levels in humans and other living systems [1]. By introducing molecular imaging probes into traditional diagnostic imaging techniques, researchers can determine the expression of indicative molecular markers at different stages of diseases. The introduction of new imaging probes, methods, and advanced imaging instrumentation is significantly speeding up the processes of drug discovery and development. The convergence of innovations has created more sensitive, specific and higher resolution measurements within living organism, especially small animals. This is expected to improve a wide range of discovery activities such as target biology, compound screening, pharmacokinetics (PK), and pharmacodynamics (PD) evaluation in animal disease models and, eventually, clinical trials. In this chapter, we will summarize and evaluate the applications of various advanced small animal imaging techniques in drug development process.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mankoff DA (2007) A definition of molecular imaging. J Nucl Med 48:18N, 21N.

    Google Scholar 

  2. Zambrowicz BP, Sands AT (2003) Knockouts model the 100 best-selling drug--ill they model the next 100? Nat Rev Drug Discov 2:38-51.

    CAS  PubMed  Google Scholar 

  3. Dimasi JA (2001) New drug development in the United States from 1963 to 1999. Clin Pharmacol Ther 69:286-96.

    CAS  PubMed  Google Scholar 

  4. DiMasi JA, Hansen RW, Grabowski HG (2003) The price of innovation: new estimates of drug development costs. J Health Econ 22:151-85.

    PubMed  Google Scholar 

  5. Seddon BM, Workman P (2003) The role of functional and molecular imaging in cancer drug discovery and development. Br J Radiol 76 Spec No 2:S128-38.

    Google Scholar 

  6. Butcher SP (2003) Target discovery and validation in the post-genomic era. Neurochem Res 28:367-71.

    CAS  PubMed  Google Scholar 

  7. MacBeath G, Schreiber SL (2000) Printing proteins as microarrays for high-throughput function determination. Science 289:1760-3.

    CAS  PubMed  Google Scholar 

  8. Andricopulo AD, Montanari CA (2005) Structure-activity relationships for the design of small-molecule inhibitors. Mini Rev Med Chem 5:585-93.

    CAS  PubMed  Google Scholar 

  9. Ertl P, Schuffenhauer A (2008) Cheminformatics analysis of natural products: lessons from nature inspiring the design of new drugs. Prog Drug Res 66:217, 219-35.

    Google Scholar 

  10. Montelione GT (2001) Structural genomics: an approach to the protein folding problem. Proc Natl Acad Sci U S A 98:13488-9.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Smith A (2002) Screening for drug discovery: The leading question. Nature 418:453-459.

    PubMed  Google Scholar 

  12. Gregory SG, Sekhon M, Schein J, Zhao S, Osoegawa K, Scott CE, et al. (2002) A physical map of the mouse genome. Nature 418:743-50.

    CAS  PubMed  Google Scholar 

  13. Polites HG (1996) Transgenic model applications to drug discovery. Int J Exp Pathol 77:257-62.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang W, Feng JQ, 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 10:423-34.

    CAS  PubMed  Google Scholar 

  15. Perez-Soler R, Kemp B, Wu QP, Mao L, Gomez J, Zeleniuch-Jacquotte A, et al. (2000) Response and determinants of sensitivity to paclitaxel in human non-small cell lung cancer tumors heterotransplanted in nude mice. Clin Cancer Res 6:4932-8.

    CAS  PubMed  Google Scholar 

  16. Massoud TF, Gambhir SS (2007) Integrating noninvasive molecular imaging into molecular medicine: an evolving paradigm. Trends Mol Med 13:183-91.

    CAS  PubMed  Google Scholar 

  17. Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207-14.

    CAS  PubMed  Google Scholar 

  18. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-16.

    CAS  PubMed  Google Scholar 

  19. Gelmon KA, Eisenhauer EA, Harris AL, Ratain MJ, Workman P (1999) Anticancer agents targeting signaling molecules and cancer cell environment: challenges for drug development? J Natl Cancer Inst 91:1281-7.

    CAS  PubMed  Google Scholar 

  20. Padhani AR, Ollivier L (2001) The RECIST (Response Evaluation Criteria in Solid Tumors) criteria: implications for diagnostic radiologists. Br J Radiol 74:983-6.

    CAS  PubMed  Google Scholar 

  21. Hoekstra CJ, Hoekstra OS, Stroobants SG, Vansteenkiste J, Nuyts J, Smit EF, et al. (2002) Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET. J Nucl Med 43:1304-9.

    CAS  PubMed  Google Scholar 

  22. Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 17:545-80.

    CAS  PubMed  Google Scholar 

  23. Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS (2008) Molecular imaging in drug development. Nat Rev Drug Discov 7:591-607.

    CAS  PubMed  Google Scholar 

  24. Price P, Jones T (2002) Molecular imaging: what picture does it paint for future oncology? Drug Discov Today 7:741-3.

    PubMed  Google Scholar 

  25. Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, et al. (2000) A combined PET/CT scanner for clinical oncology. J Nucl Med 41:1369-79.

    CAS  PubMed  Google Scholar 

  26. Even-Sapir E, Lerman H, Lievshitz G, Khafif A, Fliss DM, Schwartz A, et al. (2003) Lymphoscintigraphy for sentinel node mapping using a hybrid SPECT/CT system. J Nucl Med 44:1413-20.

    PubMed  Google Scholar 

  27. Catana C, Wu Y, Judenhofer MS, Qi J, Pichler BJ, Cherry SR (2006) Simultaneous acquisition of multislice PET and MR images: initial results with a MR-compatible PET scanner. J Nucl Med 47:1968-76.

    PubMed  Google Scholar 

  28. Loening AM, Gambhir SS (2003) AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2:131-7.

    PubMed  Google Scholar 

  29. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, et al. (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2:561-6.

    CAS  PubMed  Google Scholar 

  30. Schechter AL, Hung MC, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, et al. (1985) The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 229:976-978.

    CAS  PubMed  Google Scholar 

  31. Tan M, Yao J, Yu D (1997) Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities. Cancer Res. 57:1199-205.

    CAS  PubMed  Google Scholar 

  32. Bacus SS, Ruby SG, Weinberg DS, Chin D, Ortiz R, Bacus JW (1990) HER-2/neu oncogene expression and proliferation in breast cancers. Am J Pathol. 137:103-11.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Wiercioch R, Balcerczak E, Byszewska E, Mirowski M (2003) Uptake of radiolabelled herceptin by experimental mammary adenocarcinoma. Nucl Med Rev Cent East Eur 6:99-103.

    PubMed  Google Scholar 

  34. Traish AM, Wotiz HH (1987) Prostatic epidermal growth factor receptors and their regulation by androgens. Endocrinology 121:1461-7.

    CAS  PubMed  Google Scholar 

  35. Solit DB, Zheng FF, Drobnjak M, Munster PN, Higgins B, Verbel D, et al. (2002) 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res 8:986-93.

    CAS  PubMed  Google Scholar 

  36. Agus DB, Akita RW, Fox WD, Lewis GD, Higgins B, Pisacane PI, et al. (2002) Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2:127-37.

    CAS  PubMed  Google Scholar 

  37. Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, et al. (2006) Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 66:1630-9.

    CAS  PubMed  Google Scholar 

  38. Saga T, Endo K, Akiyama T, Sakahara H, Koizumi M, Watanabe Y, et al. (1991) Scintigraphic detection of overexpressed c-erbB-2 protooncogene products by a class-switched murine anti-c-erbB-2 protein monoclonal antibody. Cancer Res 51:990-4.

    CAS  PubMed  Google Scholar 

  39. Orlova A, Magnusson M, Eriksson TL, Nilsson M, Larsson B, Hoiden-Guthenberg I, et al. (2006) Tumor imaging using a picomolar affinity HER2 binding affibody molecule. Cancer Res 66:4339-48.

    CAS  PubMed  Google Scholar 

  40. Tolmachev V, Nilsson FY, Widstrom C, Andersson K, Rosik D, Gedda L, et al. (2006) 111In-benzyl-DTPA-ZHER2:342, an affibody-based conjugate for in vivo imaging of HER2 expression in malignant tumors. J Nucl Med 47:846-53.

    CAS  PubMed  Google Scholar 

  41. 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 22:701-6.

    CAS  PubMed  Google Scholar 

  42. Smith-Jones PM, Solit D, Afroze F, Rosen N, Larson SM (2006) Early tumor response to Hsp90 therapy using HER2 PET: comparison with 18F-FDG PET. J Nucl Med 47:793-6.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Sollars V, Lu X, Xiao L, Wang X, Garfinkel MD, Ruden DM (2003) Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution. Nat Genet 33:70-4.

    CAS  PubMed  Google Scholar 

  44. Blankenberg FG, Mandl S, Cao YA, O'Connell-Rodwell C, Contag C, Mari C, et al. (2004) Tumor imaging using a standardized radiolabeled adapter protein docked to vascular endothelial growth factor. J Nucl Med 45:1373-80.

    CAS  PubMed  Google Scholar 

  45. Backer MV, Levashova Z, Patel V, Jehning BT, Claffey K, Blankenberg FG, et al. (2007) Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes. Nat Med

    Google Scholar 

  46. Cai W, Chen K, Mohamedali KA, Cao Q, Gambhir SS, Rosenblum MG, et al. (2006) PET of vascular endothelial growth factor receptor expression. J Nucl Med 47:2048-56.

    CAS  PubMed  Google Scholar 

  47. Dayton PA, Pearson D, Clark J, Simon S, Schumann PA, Zutshi R, et al. (2004) Ultrasonic analysis of peptide- and antibody-targeted microbubble contrast agents for molecular imaging of alphavbeta3-expressing cells. Mol Imaging 3:125-34.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Wang H, Cai W, Chen K, Li ZB, Kashefi A, He L, et al. (2007) A new PET tracer specific for vascular endothelial growth factor receptor 2. Eur J Nucl Med Mol Imaging

    Google Scholar 

  49. Nagengast WB, de Vries EG, Hospers GA, Mulder NH, de Jong JR, Hollema H, et al. (2007) In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med 48:1313-9.

    CAS  PubMed  Google Scholar 

  50. Collingridge DR, Carroll VA, Glaser M, Aboagye EO, Osman S, Hutchinson OC, et al. (2002) The development of [124I]iodinated-VG76e: a novel tracer for imaging vascular endothelial growth factor in vivo using positron emission tomography. Cancer Res 62:5912-9.

    CAS  PubMed  Google Scholar 

  51. Haubner R, Wester HJ, Reuning U, Senekowitsch-Schmidtke R, Diefenbach B, Kessler H, et al. (1999) Radiolabeled alpha(v)beta3 integrin antagonists: a new class of tracers for tumor targeting. J Nucl Med 40:1061-71.

    CAS  PubMed  Google Scholar 

  52. Haubner R, Wester HJ, Weber WA, Mang C, Ziegler SI, Goodman SL, et al. (2001) Noninvasive imaging of αvβ3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res 61:1781-5.

    CAS  PubMed  Google Scholar 

  53. Haubner R (2006) αvβ3-integrin imaging: a new approach to characterise angiogenesis? Eur J Nucl Med Mol Imaging 33 Suppl 1:54-63.

    Google Scholar 

  54. Chen X, Park R, Shahinian AH, Bading JR, Conti PS (2004) Pharmacokinetics and tumor retention of 125I-labeled RGD peptide are improved by PEGylation. Nucl Med Biol 31:11-9.

    CAS  PubMed  Google Scholar 

  55. Noiri E, Goligorsky MS, Wang GJ, Wang J, Cabahug CJ, Sharma S, et al. (1996) Biodistribution and clearance of 99mTc-labeled Arg-Gly-Asp (RGD) peptide in rats with ischemic acute renal failure. J Am Soc Nephrol 7:2682-8.

    CAS  PubMed  Google Scholar 

  56. Chen X, Hou Y, Tohme M, Park R, Khankaldyyan V, Gonzales-Gomez I, et al. (2004) Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor alphavbeta3-integrin expression. J Nucl Med 45:1776-83.

    CAS  PubMed  Google Scholar 

  57. Dijkgraaf I, Liu S, Kruijtzer JA, Soede AC, Oyen WJ, Liskamp RM, et al. (2007) Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide. Nucl Med Biol 34:29-35.

    CAS  PubMed  Google Scholar 

  58. Li ZB, Chen K, Chen X (2008) (68)Ga-labeled multimeric RGD peptides for microPET imaging of integrin αvβ3 expression. Eur J Nucl Med Mol Imaging 35:1100-8.

    CAS  PubMed  Google Scholar 

  59. van Hagen PM, Breeman WA, Bernard HF, Schaar M, Mooij CM, Srinivasan A, et al. (2000) Evaluation of a radiolabelled cyclic DTPA-RGD analogue for tumour imaging and radionuclide therapy. Int J Cancer 90:186-98.

    PubMed  Google Scholar 

  60. Boturyn D, Coll JL, Garanger E, Favrot MC, Dumy P (2004) Template assembled cyclopeptides as multimeric system for integrin targeting and endocytosis. J Am Chem Soc 126:5730-9.

    CAS  PubMed  Google Scholar 

  61. Chen X, Tohme M, Park R, Hou Y, Bading JR, Conti PS (2004) Micro-PET imaging of αvβ3-integrin expression with 18F-labeled dimeric RGD peptide. Mol Imaging 3:96-104.

    CAS  PubMed  Google Scholar 

  62. Hughes MS, Marsh JN, Zhang H, Woodson AK, Allen JS, Lacy EK, et al. (2006) Characterization of digital waveforms using thermodynamic analogs: detection of contrast-targeted tissue in vivo. IEEE Trans Ultrason Ferroelectr Freq Control 53:1609-16.

    PubMed  Google Scholar 

  63. Chen X, Park R, Tohme M, Shahinian AH, Bading JR, Conti PS (2004) MicroPET and autoradiographic imaging of breast cancer alpha v-integrin expression using 18F- and 64Cu-labeled RGD peptide. Bioconjug Chem 15:41-9.

    PubMed  Google Scholar 

  64. Chen X, Liu S, Hou Y, Tohme M, Park R, Bading JR, et al. (2004) MicroPET imaging of breast cancer alphav-integrin expression with 64Cu-labeled dimeric RGD peptides. Mol Imaging Biol 6:350-9.

    PubMed  Google Scholar 

  65. Wu Y, Zhang X, Xiong Z, Cheng Z, Fisher DR, Liu S, et al. (2005) microPET imaging of glioma integrin αvβ3 expression using 64Cu-labeled tetrameric RGD peptide. J Nucl Med 46:1707-18.

    CAS  PubMed  Google Scholar 

  66. Cai W, Niu G, Chen X (2008) Imaging of integrins as biomarkers for tumor angiogenesis. Curr Pharm Des 14:2943-73.

    CAS  PubMed  Google Scholar 

  67. Mayer-Kuckuk P, Banerjee D, Malhotra S, Doubrovin M, Iwamoto M, Akhurst T, et al. (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 U S A 99:3400-5.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Workman P (2003) How much gets there and what does it do?: The need for better pharmacokinetic and pharmacodynamic endpoints in contemporary drug discovery and development. Curr Pharm Des 9:891-902.

    CAS  PubMed  Google Scholar 

  69. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70.

    CAS  PubMed  Google Scholar 

  70. Warburg O (1956) On the origin of cancer cells. Science 123:309-14.

    CAS  PubMed  Google Scholar 

  71. Vallabhajosula S (2007) (18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization. Semin Nucl Med 37:400-19.

    PubMed  Google Scholar 

  72. Sols A, Crane RK (1954) Substrate specificity of brain hexokinase. J Biol Chem 210:581-95.

    CAS  PubMed  Google Scholar 

  73. Ichiya Y, Kuwabara Y, Otsuka M, Tahara T, Yoshikai T, Fukumura T, et al. (1991) Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography. J Nucl Med 32:1655-60.

    CAS  PubMed  Google Scholar 

  74. Berlangieri SU, Brizel DM, Scher RL, Schifter T, Hawk TC, Hamblen S, et al. (1994) Pilot study of positron emission tomography in patients with advanced head and neck cancer receiving radiotherapy and chemotherapy. Head Neck 16:340-6.

    CAS  PubMed  Google Scholar 

  75. Prenen H, Deroose C, Vermaelen P, Sciot R, Debiec-Rychter M, Stroobants S, et al. (2006) Establishment of a mouse gastrointestinal stromal tumour model and evaluation of response to imatinib by small animal positron emission tomography. Anticancer Res 26:1247-52.

    CAS  PubMed  Google Scholar 

  76. Tian M, Zhang H, Higuchi T, Oriuchi N, Inoue T, Endo K (2004) Effect of mitomycin C and vinblastine on FDG uptake of human nonsmall-cell lung cancer xenografts in nude mice. Cancer Biother Radiopharm 19:601-5.

    CAS  PubMed  Google Scholar 

  77. Tseng JR, Kang KW, Dandekar M, Yaghoubi S, Lee JH, Christensen JG, et al. (2008) Preclinical efficacy of the c-Met inhibitor CE-355621 in a U87 MG mouse xenograft model evaluated by 18F-FDG small-animal PET. J Nucl Med 49:129-34.

    PubMed  Google Scholar 

  78. Dandekar M, Tseng JR, Gambhir SS (2007) Reproducibility of 18F-FDG microPET studies in mouse tumor xenografts. J Nucl Med 48:602-7.

    PubMed  Google Scholar 

  79. Sherley JL, Kelly TJ (1988) Regulation of human thymidine kinase during the cell cycle. J Biol Chem 263:8350-8.

    CAS  PubMed  Google Scholar 

  80. Shields AF (2003) PET imaging with 18F-FLT and thymidine analogs: promise and pitfalls. J Nucl Med 44:1432-4.

    CAS  PubMed  Google Scholar 

  81. Leyton J, Latigo JR, Perumal M, Dhaliwal H, He Q, Aboagye EO (2005) Early detection of tumor response to chemotherapy by 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography: the effect of cisplatin on a fibrosarcoma tumor model in vivo. Cancer Res 65:4202-10.

    CAS  PubMed  Google Scholar 

  82. Tseng JR, Dandekar M, Subbarayan M, Cheng Z, Park JM, Louie S, et al. (2005) Reproducibility of 3'-deoxy-3'-18F-fluorothymidine microPET studies in tumor xenografts in mice. J Nucl Med 46:1851-7.

    CAS  PubMed  Google Scholar 

  83. Dimitrakopoulou-Strauss A, Strauss LG (2008) The role of 18F-FLT in cancer imaging: does it really reflect proliferation? Eur J Nucl Med Mol Imaging 35:523-6.

    PubMed  Google Scholar 

  84. Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29:15-8.

    CAS  PubMed  Google Scholar 

  85. Lassau N, Lamuraglia M, Chami L, Leclere J, Bonvalot S, Terrier P, et al. (2006) Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography. AJR Am J Roentgenol 187:1267-73.

    PubMed  Google Scholar 

  86. Li PC, Yang MJ (2003) Transfer function analysis of ultrasonic time-intensity measurements. Ultrasound Med Biol 29:1493-500.

    PubMed  Google Scholar 

  87. Lavisse S, Lejeune P, Rouffiac V, Elie N, Bribes E, Demers B, et al. (2008) Early quantitative evaluation of a tumor vasculature disruptive agent AVE8062 using dynamic contrast-enhanced ultrasonography. Invest Radiol 43:100-11.

    CAS  PubMed  Google Scholar 

  88. Miller KD, Soule SE, Calley C, Emerson RE, Hutchins GD, Kopecky K, et al. (2005) Randomized phase II trial of the anti-angiogenic potential of doxorubicin and docetaxel; primary chemotherapy as Biomarker Discovery Laboratory. Breast Cancer Res Treat 89:187-97.

    CAS  PubMed  Google Scholar 

  89. Padhani AR (2003) MRI for assessing antivascular cancer treatments. Br J Radiol 76 Spec No 1:S60-80.

    Google Scholar 

  90. Zhang C, Jugold M, Woenne EC, Lammers T, Morgenstern B, Mueller MM, et al. (2007) Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. Cancer Res 67:1555-62.

    CAS  PubMed  Google Scholar 

  91. Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E, Knopp MV, et al. (1999) Estimating kinetic parameters from dynamic contrast-enhanced T1-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10:223-32.

    CAS  PubMed  Google Scholar 

  92. Padhani AR, Husband JE (2001) Dynamic contrast-enhanced MRI studies in oncology with an emphasis on quantification, validation and human studies. Clin Radiol 56:607-20.

    CAS  PubMed  Google Scholar 

  93. Barrett T, Brechbiel M, Bernardo M, Choyke PL (2007) MRI of tumor angiogenesis. J Magn Reson Imaging 26:235-49.

    PubMed  Google Scholar 

  94. Liu G, Rugo HS, Wilding G, McShane TM, Evelhoch JL, Ng C, et al. (2005) Dynamic contrast-enhanced magnetic resonance imaging as a pharmacodynamic measure of response after acute dosing of AG-013736, an oral angiogenesis inhibitor, in patients with advanced solid tumors: results from a phase I study. J Clin Oncol 23:5464-73.

    CAS  PubMed  Google Scholar 

  95. Thomas AL, Morgan B, Horsfield MA, Higginson A, Kay A, Lee L, et al. (2005) Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J Clin Oncol 23:4162-71.

    CAS  PubMed  Google Scholar 

  96. Medved M, Karczmar G, Yang C, Dignam J, Gajewski TF, Kindler H, et al. (2004) Semiquantitative analysis of dynamic contrast enhanced MRI in cancer patients: Variability and changes in tumor tissue over time. J Magn Reson Imaging 20:122-8.

    PubMed  Google Scholar 

  97. Marzola P, Degrassi A, Calderan L, Farace P, Crescimanno C, Nicolato E, et al. (2004) In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model. Clin Cancer Res 10:739-50.

    CAS  PubMed  Google Scholar 

  98. Faccioli N, Marzola P, Boschi F, Sbarbati A, D'Onofrio M, Pozzi Mucelli R (2007) Pathological animal models in the experimental evaluation of tumour microvasculature with magnetic resonance imaging. Radiol Med (Torino) 112:319-28.

    CAS  Google Scholar 

  99. Tatum JL, Kelloff GJ, Gillies RJ, Arbeit JM, Brown JM, Chao KS, et al. (2006) Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy. Int J Radiat Biol 82:699-757.

    CAS  PubMed  Google Scholar 

  100. Stone HB, Brown JM, Phillips TL, Sutherland RM (1993) Oxygen in human tumors: correlations between methods of measurement and response to therapy. Summary of a workshop held November 19-20, 1992, at the National Cancer Institute, Bethesda, Maryland. Radiat Res 136:422-34.

    CAS  PubMed  Google Scholar 

  101. Foo SS, Abbott DF, Lawrentschuk N, Scott AM (2004) Functional imaging of intratumoral hypoxia. Mol Imaging Biol 6:291-305.

    PubMed  Google Scholar 

  102. Vikram DS, Zweier JL, Kuppusamy P (2007) Methods for noninvasive imaging of tissue hypoxia. Antioxid Redox Signal 9:1745-56.

    CAS  PubMed  Google Scholar 

  103. Laking GR, Price PM (2003) Positron emission tomographic imaging of angiogenesis and vascular function. Br J Radiol 76 Spec No 1:S50-9.

    Google Scholar 

  104. Lee ST, Scott AM (2007) Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole. Semin Nucl Med 37:451-61.

    PubMed  Google Scholar 

  105. Lawrentschuk N, Poon AM, Foo SS, Putra LG, Murone C, Davis ID, et al. (2005) Assessing regional hypoxia in human renal tumours using 18F-fluoromisonidazole positron emission tomography. BJU Int 96:540-6.

    PubMed  Google Scholar 

  106. Zimny M, Gagel B, Dimartino E, Hamacher K, Coenen HH, Westhofen M, et al. (2006) FDG-a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO (2)-polarography in metastatic head and neck cancer. Eur J Nucl Med Mol Imaging 33:1426-31.

    CAS  PubMed  Google Scholar 

  107. Koh WJ, Rasey JS, Evans ML, Grierson JR, Lewellen TK, Graham MM, et al. (1992) Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. Int J Radiat Oncol Biol Phys 22:199-212.

    CAS  PubMed  Google Scholar 

  108. Rasey JS, Koh WJ, Evans ML, Peterson LM, Lewellen TK, Graham MM, et al. (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 36:417-28.

    CAS  PubMed  Google Scholar 

  109. Markus R, Reutens DC, Kazui S, Read S, Wright P, Pearce DC, et al. (2004) Hypoxic tissue in ischaemic stroke: persistence and clinical consequences of spontaneous survival. Brain 127:1427-36.

    CAS  PubMed  Google Scholar 

  110. Sorger D, Patt M, Kumar P, Wiebe LI, Barthel H, Seese A, et al. (2003) [F-18]Fluoroazomycinarabinofuranoside (18FAZA) and [F-18]Fluoromisonidazole ((FMISO)-F-18): A comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors. Nuclear Medicine and Biology 30:317-326.

    CAS  PubMed  Google Scholar 

  111. Gronroos T, Bentzen L, Marjamaki P, Murata R, Horsman MR, Keiding S, et al. (2004) Comparison of the biodistribution of two hypoxia markers [F-18]FETNIM and [F-18]FMISO in an experimental mammary carcinoma. European Journal of Nuclear Medicine and Molecular Imaging 31:513-520.

    PubMed  Google Scholar 

  112. Piert M, Machulla HJ, Picchio M, Reischl G, Ziegler S, Kumar P, et al. (2005) Hypoxia-specific tumor imaging with F-18-fluoroazomycin arabinoside. Journal of Nuclear Medicine 46:106-113.

    PubMed  Google Scholar 

  113. Ziemer LS, Evans SM, Kachur A, Shuman AL, Cardi CA, Jenkins WT, et al. (2003) Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole F-18-EF5. European Journal of Nuclear Medicine and Molecular Imaging 30:259-266.

    CAS  PubMed  Google Scholar 

  114. Koch CJ (2002) Measurement of absolute oxygen levels in cells and tissues using oxygen sensors and 2-nitroimidazole EF5. Methods Enzymol 352:3-31.

    CAS  PubMed  Google Scholar 

  115. Evans SM, Jenkins WT, Joiner B, Lord EM, Koch CJ (1996) 2-Nitroimidazole (EF5) binding predicts radiation resistance in individual 9L s.c. tumors. Cancer Res 56:405-11.

    CAS  PubMed  Google Scholar 

  116. Kachur AV, Dolbier WR, Jr., Evans SM, Shiue CY, Shiue GG, Skov KA, et al. (1999) Synthesis of new hypoxia markers EF1 and [18F]-EF1. Appl Radiat Isot 51:643-50.

    CAS  PubMed  Google Scholar 

  117. Evans SM, Kachur AV, Shiue CY, Hustinx R, Jenkins WT, Shive GG, et al. (2000) Noninvasive detection of tumor hypoxia using the 2-nitroimidazole [18F]EF1. J Nucl Med 41:327-36.

    CAS  PubMed  Google Scholar 

  118. Dolbier WR, Jr., Li AR, Koch CJ, Shiue CY, Kachur AV (2001) [18F]-EF5, a marker for PET detection of hypoxia: synthesis of precursor and a new fluorination procedure. Appl Radiat Isot 54:73-80.

    CAS  PubMed  Google Scholar 

  119. Josse O, Labar D, Georges B, Gregoire V, Marchand-Brynaert J (2001) Synthesis of [18F]-labeled EF3 [2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)-acetamide], a marker for PET detection of hypoxia. Bioorg Med Chem 9:665-75.

    CAS  PubMed  Google Scholar 

  120. Mahy P, De Bast M, Leveque PH, Gillart J, Labar D, Marchand J, et al. (2004) Preclinical validation of the hypoxia tracer 2-(2-nitroimidazol-1-yl)- N-(3,3,3-[18F]trifluoropropyl)acetamide, [18F]EF3. Eur J Nucl Med Mol Imaging 31:1263-72.

    CAS  PubMed  Google Scholar 

  121. Dubois L, Landuyt W, Cloetens L, Bol A, Bormans G, Haustermans K, et al. (2008) [18F]EF3 is not superior to [18F]FMISO for PET-based hypoxia evaluation as measured in a rat rhabdomyosarcoma tumour model. Eur J Nucl Med Mol Imaging

    Google Scholar 

  122. Vavere AL, Lewis JS (2007) Cu-ATSM: a radiopharmaceutical for the PET imaging of hypoxia. Dalton Trans:4893-902.

    Google Scholar 

  123. Dehdashti F, Grigsby PW, Mintun MA, Lewis JS, Siegel BA, Welch MJ (2003) Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: relationship to therapeutic response-a preliminary report. Int J Radiat Oncol Biol Phys 55:1233-8.

    PubMed  Google Scholar 

  124. Dehdashti F, Mintun MA, Lewis JS, Bradley J, Govindan R, Laforest R, et al. (2003) In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM. Eur J Nucl Med Mol Imaging 30:844-50.

    CAS  PubMed  Google Scholar 

  125. Bayly SR, King RC, Honess DJ, Barnard PJ, Betts HM, Holland JP, et al. (2008) In Vitro and In Vivo Evaluations of a Hydrophilic 64Cu-Bis(Thiosemicarbazonato)-Glucose Conjugate for Hypoxia Imaging. J Nucl Med

    Google Scholar 

  126. Henson PM, Hume DA (2006) Apoptotic cell removal in development and tissue homeostasis. Trends Immunol 27:244-50.

    CAS  PubMed  Google Scholar 

  127. Schoenberger J, Bauer J, Moosbauer J, Eilles C, Grimm D (2008) Innovative strategies in in vivo apoptosis imaging. Curr Med Chem 15:187-94.

    CAS  PubMed  Google Scholar 

  128. Hsu AR, Cai W, Veeravagu A, Mohamedali KA, Chen K, Kim S, et al. (2007) Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel. J Nucl Med 48:445-54.

    CAS  PubMed  Google Scholar 

  129. Evan GI, Vousden KH (2001) Proliferation, cell cycle and apoptosis in cancer. Nature 411:342-8.

    CAS  PubMed  Google Scholar 

  130. Lahorte CM, Vanderheyden JL, Steinmetz N, Van de Wiele C, Dierckx RA, Slegers G (2004) Apoptosis-detecting radioligands: current state of the art and future perspectives. Eur J Nucl Med Mol Imaging 31:887-919.

    CAS  PubMed  Google Scholar 

  131. Wolters SL, Corsten MF, Reutelingsperger CP, Narula J, Hofstra L (2007) Cardiovascular molecular imaging of apoptosis. Eur J Nucl Med Mol Imaging 34 Suppl 1:S86-98.

    CAS  PubMed  Google Scholar 

  132. Boersma HH, Kietselaer BL, Stolk LM, Bennaghmouch A, Hofstra L, Narula J, et al. (2005) Past, present, and future of annexin A5: from protein discovery to clinical applications. J Nucl Med 46:2035-50.

    CAS  PubMed  Google Scholar 

  133. Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K, et al. (1998) In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci U S A 95:6349-54.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Blankenberg FG, Naumovski L, Tait JF, Post AM, Strauss HW (2001) Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc-radiolabeled annexin V. J Nucl Med 42:309-16.

    CAS  PubMed  Google Scholar 

  135. Blankenberg FG, Robbins RC, Stoot JH, Vriens PW, Berry GJ, Tait JF, et al. (2000) Radionuclide imaging of acute lung transplant rejection with annexin V. Chest 117:834-40.

    CAS  PubMed  Google Scholar 

  136. Yang DJ, Azhdarinia A, Wu P, Yu DF, Tansey W, Kalimi SK, et al. (2001) In vivo and in vitro measurement of apoptosis in breast cancer cells using 99mTc-EC-annexin V. Cancer Biother Radiopharm 16:73-83.

    PubMed  Google Scholar 

  137. Zhu X, Li Z, Zhao M (2007) Imaging acute cardiac cell death: temporal and spatial distribution of 99mTc-labeled C2A in the area at risk after myocardial ischemia and reperfusion. J Nucl Med 48:1031-6.

    CAS  PubMed  Google Scholar 

  138. Shao R, Xiong C, Wen X, Gelovani JG, Li C (2007) Targeting phosphatidylserine on apoptotic cells with phages and peptides selected from a bacteriophage display library. Mol Imaging 6:417-26.

    CAS  PubMed  Google Scholar 

  139. Tait JF (2008) Imaging of apoptosis. J Nucl Med 49:1573-6.

    PubMed  Google Scholar 

  140. Tait JF, Smith C, Levashova Z, Patel B, Blankenberg FG, Vanderheyden JL (2006) Improved detection of cell death in vivo with annexin V radiolabeled by site-specific methods. J Nucl Med 47:1546-53.

    CAS  PubMed  Google Scholar 

  141. Yagle KJ, Eary JF, Tait JF, Grierson JR, Link JM, Lewellen B, et al. (2005) Evaluation of 18F-annexin V as a PET imaging agent in an animal model of apoptosis. J Nucl Med 46:658-66.

    CAS  PubMed  Google Scholar 

  142. Riedl SJ, Shi Y (2004) Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 5:897-907.

    CAS  PubMed  Google Scholar 

  143. Grutter MG (2000) Caspases: key players in programmed cell death. Curr Opin Struct Biol 10:649-55.

    CAS  PubMed  Google Scholar 

  144. Angres B, Steuer H, Weber P, Wagner M, Schneckenburger H (2008) A membrane-bound FRET-based caspase sensor for detection of apoptosis using fluorescence lifetime and total internal reflection microscopy. Cytometry A

    Google Scholar 

  145. Ray P, De A, Patel M, Gambhir SS (2008) Monitoring caspase-3 activation with a multimodality imaging sensor in living subjects. Clin Cancer Res 14:5801-9.

    CAS  PubMed  Google Scholar 

  146. Coppola JM, Ross BD, Rehemtulla A (2008) Noninvasive imaging of apoptosis and its application in cancer therapeutics. Clin Cancer Res 14:2492-501.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Lovqvist A, Humm JL, Sheikh A, Finn RD, Koziorowski J, Ruan S, et al. (2001) PET imaging of 86Y-labeled anti-Lewis Y monoclonal antibodies in a nude mouse model: comparison between (86)Y and (111)In radiolabels. J Nucl Med 42:1281-7.

    CAS  PubMed  Google Scholar 

  148. Sunkuk K, Shi K, Houston JP, Wei W, Qingping W, Chun L, et al. (2005) Imaging dose-dependent pharmacokinetics of an RGD-fluorescent dye conjugate targeted to αvβ3 receptor expressed in Kaposi's sarcoma. Mol Imaging 4:75-87.

    Google Scholar 

  149. Kopka K, Faust A, Keul P, Wagner S, Breyholz HJ, Holtke C, et al. (2006) 5-pyrrolidinylsulfonyl isatins as a potential tool for the molecular imaging of caspases in apoptosis. J Med Chem 49:6704-15.

    CAS  PubMed  Google Scholar 

  150. Smith G, Glaser M, Perumal M, Nguyen QD, Shan B, Arstad E, et al. (2008) Design, synthesis, and biological characterization of a caspase 3/7 selective isatin labeled with 2-[18F]fluoroethylazide. J Med Chem 51:8057-67.

    CAS  PubMed  Google Scholar 

  151. Zhou D, Chu W, Rothfuss J, Zeng C, Xu J, Jones L, et al. (2006) Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis. Bioorg Med Chem Lett 16:5041-6.

    CAS  PubMed  Google Scholar 

  152. Min JJ, Biswal S, Deroose C, Gambhir SS (2004) Tetraphenylphosphonium as a novel molecular probe for imaging tumors. J Nucl Med 45:636-43.

    CAS  PubMed  Google Scholar 

  153. Madar I, Ravert H, Nelkin B, Abro M, Pomper M, Dannals R, et al. (2007) Characterization of membrane potential-dependent uptake of the novel PET tracer 18F-fluorobenzyl triphenylphosphonium cation. Eur J Nucl Med Mol Imaging 34:2057-65.

    CAS  PubMed  Google Scholar 

  154. Nollen EA, Morimoto RI (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing 'heat shock' proteins. J Cell Sci 115:2809-16.

    CAS  PubMed  Google Scholar 

  155. Citri A, Alroy I, Lavi S, Rubin C, Xu W, Grammatikakis N, et al. (2002) Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy. Embo J 21:2407-17.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Murakami Y, Mizuno S, Uehara Y (1994) Accelerated degradation of 160 kDa epidermal growth factor (EGF) receptor precursor by the tyrosine kinase inhibitor herbimycin A in the endoplasmic reticulum of A431 human epidermoid carcinoma cells. The Biochemical journal 301 (Pt 1):63-68.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Sakagami M, Morrison P, Welch WJ (1999) Benzoquinoid ansamycins (herbimycin A and geldanamycin) interfere with the maturation of growth factor receptor tyrosine kinases. Cell Stress Chaperones 4:19-28.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Cai W, Chen K, He L, Cao Q, Koong A, Chen X (2007) Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody. Eur J Nucl Med Mol Imaging 34:850-858.

    CAS  PubMed  Google Scholar 

  159. Niu G, Cai W, Chen K, Chen X (2008) Non-Invasive PET Imaging of EGFR Degradation Induced by a Heat Shock Protein 90 Inhibitor. Mol Imaging Biol 10:99-106.

    PubMed  Google Scholar 

  160. Lemmon MA, Schlessinger J (1994) Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci 19:459-63.

    CAS  PubMed  Google Scholar 

  161. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4:988-1004.

    CAS  PubMed  Google Scholar 

  162. Kondapaka SB, Singh SS, Dasmahapatra GP, Sausville EA, Roy KK (2003) Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Mol Cancer Ther 2:1093-103.

    CAS  PubMed  Google Scholar 

  163. Han Z, Fu A, Wang H, Diaz R, Geng L, Onishko H, et al. (2008) Noninvasive assessment of cancer response to therapy. Nat Med 14:343-9.

    CAS  PubMed  Google Scholar 

  164. Miller AD (1990) Progress toward human gene therapy. Blood 76:271-8.

    CAS  PubMed  Google Scholar 

  165. Kootstra NA, Verma IM (2003) Gene therapy with viral vectors. Annu Rev Pharmacol Toxicol 43:413-39.

    CAS  PubMed  Google Scholar 

  166. Kristian Raty J, Liimatainen T, Unelma Kaikkonen M, Grohn O, Airenne KJ, Yla-Herttuala S (2007) Non-invasive Imaging in Gene Therapy. Mol Ther 15:1579-86.

    Google Scholar 

  167. Massoud TF, Singh A, Gambhir SS (2008) Noninvasive molecular neuroimaging using reporter genes: part I, principles revisited. AJNR Am J Neuroradiol 29:229-34.

    CAS  PubMed  Google Scholar 

  168. Liang Q, Nguyen K, Satyamurthy N, Barrio JR, Phelps ME, Gambhir SS, et al. (2002) Monitoring adenoviral DNA delivery, using a mutant herpes simplex virus type 1 thymidine kinase gene as a PET reporter gene. Gene Ther 9:1659-66.

    CAS  PubMed  Google Scholar 

  169. Niu G, Krager KJ, Graham MM, Hichwa RD, Domann FE (2005) Noninvasive radiological imaging of pulmonary gene transfer and expression using the human sodium iodide symporter. Eur J Nucl Med Mol Imaging 32:534-40.

    CAS  PubMed  Google Scholar 

  170. Niu G, Anderson RD, Madsen MT, Graham MM, Oberley LW, Domann FE (2006) Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer. Nucl Med Biol 33:391-8.

    CAS  PubMed  Google Scholar 

  171. Wunderbaldinger P, Bogdanov A, Weissleder R (2000) New approaches for imaging in gene therapy. Eur J Radiol 34:156-65.

    CAS  PubMed  Google Scholar 

  172. Rome C, Couillaud F, Moonen CT (2005) Spatial and temporal control of expression of therapeutic genes using heat shock protein promoters. Methods 35:188-98.

    CAS  PubMed  Google Scholar 

  173. Blackburn RV, Galoforo SS, Corry PM, Lee YJ (1998) Adenoviral-mediated transfer of a heat-inducible double suicide gene into prostate carcinoma cells. Cancer Res 58:1358-62.

    CAS  PubMed  Google Scholar 

  174. Dong D, Dubeau L, Bading J, Nguyen K, Luna M, Yu H, et al. (2004) Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors. Hum Gene Ther 15:553-61.

    CAS  PubMed  Google Scholar 

  175. Huang Q, Hu JK, Lohr F, Zhang L, Braun R, Lanzen J, et al. (2000) Heat-induced gene expression as a novel targeted cancer gene therapy strategy. Cancer Res 60:3435-9.

    CAS  PubMed  Google Scholar 

  176. Vekris A, Maurange C, Moonen C, Mazurier F, De Verneuil H, Canioni P, et al. (2000) Control of transgene expression using local hyperthermia in combination with a heat-sensitive promoter. J Gene Med 2:89-96.

    CAS  PubMed  Google Scholar 

  177. Borrelli MJ, Schoenherr DM, Wong A, Bernock LJ, Corry PM (2001) Heat-activated transgene expression from adenovirus vectors infected into human prostate cancer cells. Cancer Res 61:1113-21.

    CAS  PubMed  Google Scholar 

  178. Guilhon E, Quesson B, Moraud-Gaudry F, de Verneuil H, Canioni P, Salomir R, et al. (2003) Image-guided control of transgene expression based on local hyperthermia. Mol Imaging 2:11-7.

    CAS  PubMed  Google Scholar 

  179. Wang S, Xie W, Rylander MN, Tucker PW, Aggarwal S, Diller KR (2008) HSP70 kinetics study by continuous observation of HSP-GFP fusion protein expression on a perfusion heating stage. Biotechnol Bioeng 99:146-54.

    CAS  PubMed  Google Scholar 

  180. Niu G, Gaut AW, Ponto LL, Hichwa RD, Madsen MT, Graham MM, et al. (2004) Multimodality noninvasive imaging of gene transfer using the human sodium iodide symporter. J Nucl Med 45:445-9.

    CAS  PubMed  Google Scholar 

  181. Che J, Doubrovin M, Serganova I, Ageyeva L, Beresten T, Finn R, et al. (2007) HSP70-inducible hNIS-IRES-eGFP reporter imaging: response to heat shock. Mol Imaging 6:404-16.

    CAS  PubMed  Google Scholar 

  182. Genove G, DeMarco U, Xu H, Goins WF, Ahrens ET (2005) A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 11:450-4.

    CAS  PubMed  Google Scholar 

  183. Cohen B, Dafni H, Meir G, Harmelin A, Neeman M (2005) Ferritin as an endogenous MRI reporter for noninvasive imaging of gene expression in C6 glioma tumors. Neoplasia 7:109-17.

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Workman P (2001) New drug targets for genomic cancer therapy: successes, limitations, opportunities and future challenges. Curr Cancer Drug Targets 1:33-47.

    CAS  PubMed  Google Scholar 

  185. Halldin C, Gulyas B, Farde L (2001) PET studies with carbon-11 radioligands in neuropsychopharmacological drug development. Curr Pharm Des 7:1907-29.

    CAS  PubMed  Google Scholar 

  186. Fischman AJ, Alpert NM, Rubin RH (2002) Pharmacokinetic imaging: a noninvasive method for determining drug distribution and action. Clin Pharmacokinet 41:581-602.

    CAS  PubMed  Google Scholar 

  187. Aboagye EO, Price PM, Jones T (2001) In vivo pharmacokinetics and pharmacodynamics in drug development using positron-emission tomography. Drug Discov Today 6:293-302.

    CAS  PubMed  Google Scholar 

  188. Machka K, Braveny I (1987) Comparative in vitro activity of RO 23-6240 (fleroxacin), a new 4-quinolone derivative. Eur J Clin Microbiol 6:482-5.

    CAS  PubMed  Google Scholar 

  189. Fischman AJ, Livni E, Babich J, Alpert NM, Liu YY, Thom E, et al. (1992) Pharmacokinetics of 18F-labeled fleroxacin in rabbits with Escherichia coli infections, studied with positron emission tomography. Antimicrob Agents Chemother 36:2286-92.

    CAS  PubMed  PubMed Central  Google Scholar 

  190. Rubin RH, Livni E, Babich J, Alpert NM, Liu YY, Tham E, et al. (1993) Pharmacokinetics of fleroxacin as studied by positron emission tomography and [18F]fleroxacin. Am J Med 94:31S-37S.

    CAS  PubMed  Google Scholar 

  191. Fischman AJ, Livni E, Babich JW, Alpert NM, Bonab A, Chodosh S, et al. (1996) Pharmacokinetics of [18F]fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography. Antimicrob Agents Chemother 40:659-64.

    CAS  PubMed  PubMed Central  Google Scholar 

  192. Tyler JL, Yamamoto YL, Diksic M, Theron J, Villemure JG, Worthington C, et al. (1986) Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET. J Nucl Med 27:775-80.

    CAS  PubMed  Google Scholar 

  193. Veenendaal LM, Jin H, Ran S, Cheung L, Navone N, Marks JW, et al. (2002) In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors. Proc Natl Acad Sci U S A 99:7866-71.

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Wiseman GA, Kornmehl E, Leigh B, Erwin WD, Podoloff DA, Spies S, et al. (2003) Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: combined data from 4 clinical trials. J Nucl Med 44:465-74.

    CAS  PubMed  Google Scholar 

  195. Garmestani K, Milenic DE, Plascjak PS, Brechbiel MW (2002) A new and convenient method for purification of 86Y using a Sr(II) selective resin and comparison of biodistribution of 86Y and 111In labeled Herceptin. Nucl Med Biol 29:599-606.

    CAS  PubMed  Google Scholar 

  196. van Gog FB, Visser GW, Klok R, van der Schors R, Snow GB, van Dongen GA (1996) Monoclonal antibodies labeled with rhenium-186 using the MAG3 chelate: relationship between the number of chelated groups and biodistribution characteristics. The Journal of nuclear medicine 37:352-362.

    Google Scholar 

  197. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701-5.

    CAS  PubMed  Google Scholar 

  198. Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, et al. (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913-8.

    PubMed  Google Scholar 

  199. Wang H, Chen X (2008) Imaging mesenchymal stem cell migration and the implications for stem cell-based cancer therapies. Future Oncol 4:623-8.

    PubMed  Google Scholar 

  200. Aicher A, Brenner W, Zuhayra M, Badorff C, Massoudi S, Assmus B, et al. (2003) Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 107:2134-9.

    PubMed  Google Scholar 

  201. Adonai N, Nguyen KN, Walsh J, Iyer M, Toyokuni T, Phelps ME, et al. (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 U S A 99:3030-5.

    CAS  PubMed  PubMed Central  Google Scholar 

  202. Ma B, Hankenson KD, Dennis JE, Caplan AI, Goldstein SA, Kilbourn MR (2005) A simple method for stem cell labeling with fluorine 18. Nucl Med Biol 32:701-5.

    CAS  PubMed  Google Scholar 

  203. Drevs J, Hofmann I, Hugenschmidt H, Wittig C, Madjar H, Muller M, et al. (2000) Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model. Cancer Res 60:4819-24.

    CAS  PubMed  Google Scholar 

  204. Bulte JW, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484-99.

    CAS  PubMed  Google Scholar 

  205. Partlow KC, Chen J, Brant JA, Neubauer AM, Meyerrose TE, Creer MH, et al. (2007) 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. Faseb J 21:1647-54.

    CAS  PubMed  Google Scholar 

  206. Amado LC, Saliaris AP, Schuleri KH, St John M, Xie JS, Cattaneo S, et al. (2005) Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 102:11474-9.

    CAS  PubMed  PubMed Central  Google Scholar 

  207. Pearl J, Wu JC (2008) Seeing is believing: tracking cells to determine the effects of cell transplantation. Semin Thorac Cardiovasc Surg 20:102-9.

    PubMed  Google Scholar 

  208. Degano IR, Vilalta M, Bago JR, Matthies AM, Hubbell JA, Dimitriou H, et al. (2008) Bioluminescence imaging of calvarial bone repair using bone marrow and adipose tissue-derived mesenchymal stem cells. Biomaterials 29:427-37.

    CAS  PubMed  Google Scholar 

  209. Vilalta M, Degano IR, Bago J, Gould D, Santos M, Garcia-Arranz M, et al. (2008) Biodistribution, long-term survival, and safety of human adipose tissue-derived mesenchymal stem cells transplanted in nude mice by high sensitivity non-invasive bioluminescence imaging. Stem Cells Dev 17:993-1003.

    PubMed  Google Scholar 

  210. Hwang do W, Jang SJ, Kim YH, Kim HJ, Shim IK, Jeong JM, et al. (2008) Real-time in vivo monitoring of viable stem cells implanted on biocompatible scaffolds. Eur J Nucl Med Mol Imaging 35:1887-98.

    Google Scholar 

  211. Li Z, Suzuki Y, Huang M, Cao F, Xie X, Connolly AJ, et al. (2008) Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects. Stem Cells 26:864-73.

    CAS  PubMed  PubMed Central  Google Scholar 

  212. Chen IY, Greve JM, Gheysens O, Willmann JK, Rodriguez-Porcel M, Chu P, et al. (2008) Comparison of Optical Bioluminescence Reporter Gene and Superparamagnetic Iron Oxide MR Contrast Agent as Cell Markers for Noninvasive Imaging of Cardiac Cell Transplantation. Mol Imaging Biol

    Google Scholar 

  213. Schellens JH, Malingre MM, Kruijtzer CM, Bardelmeijer HA, van Tellingen O, Schinkel AH, et al. (2000) Modulation of oral bioavailability of anticancer drugs: from mouse to man. Eur J Pharm Sci 12:103-10.

    CAS  PubMed  Google Scholar 

  214. Nomura T, Tamaoki N, Takakura A, Suemizu H (2008) Basic concept of development and practical application of animal models for human diseases. Curr Top Microbiol Immunol 324:1-24.

    CAS  PubMed  Google Scholar 

  215. Cao T, Leroux-Roels G (2000) Antigen-specific T cell responses in human peripheral blood leucocyte (hu-PBL)-mouse chimera conditioned with radiation and an antibody directed against the mouse IL-2 receptor beta-chain. Clin Exp Immunol 122:117-23.

    CAS  PubMed  PubMed Central  Google Scholar 

  216. Pearson T, Greiner DL, Shultz LD (2008) Humanized SCID mouse models for biomedical research. Curr Top Microbiol Immunol 324:25-51.

    CAS  PubMed  Google Scholar 

  217. Pomper MG, Lee JS (2005) Small animal imaging in drug development. Curr Pharm Des 11:3247-72.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This project was supported by National Institute of Biomedical Imaging and Bioengineering (NIBIB) (R21 EB001785), National Cancer Institute (NCI) (R21 CA102123, P50 CA114747, U54 CA119367, and R24 CA93862), Department of Defense (DOD) (W81XWH-04-1-0697, W81XWH-06-1-0665, W81XWH-06-1-0042, and DAMD17-03-1-0143), and a DOD Prostate Postdoctoral Fellowship from Department of Defense (to G. Niu).

Author information

Authors and Affiliations

  1. National Institute Biomedical Imaging and Bioengineering (NIBIB), NIH, Bethesda, MD, USA

    Gang Niu

  2. National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, USA

    Xiaoyuan Chen

Authors
  1. Gang Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoyuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaoyuan Chen .

Editor information

Editors and Affiliations

  1. Department of Radiology & Medical Informatics, Geneva University Hospital, Geneva, Switzerland

    Habib Zaidi

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Niu, G., Chen, X. (2014). Applications of Small-Animal Molecular Imaging in Drug Development. In: Zaidi, H. (eds) Molecular Imaging of Small Animals. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0894-3_24

Download citation

Publish with us

Policies and ethics

Search

Navigation