Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Molecular imaging in drug development

Key Points

  • Drug development is a costly, time-intensive and high-risk endeavour, with only two to three approvals for novel therapeutics in new drug classes per year eventually making it to market. New strategies are required to identify promising new drug candidates early on and, likewise, to terminate those candidates that are unlikely to be successful, thus allowing a more rapid and efficient move to pivotal trials.

  • Molecular imaging attempts to characterize and quantify biological processes at the cellular and subcellular level in intact living subjects. It exploits specific molecular probes and intrinsic tissue characteristics as the source of image contrast, providing the potential for understanding of integrative biology, earlier detection and characterization of disease, and evaluation of treatment.

  • As most molecular imaging techniques are routine in clinical radiology departments and have counterparts in the experimental research setting, it is possible to design preclinical experiments that not only predict clinical imaging observations but also provide a mechanistic understanding of the observed biological response.

  • Molecular imaging has the potential to have a significant impact on different phases of drug development, including target expression, compound screening and optimization, as well as Phases I to III clinical studies. Examples are detailed in the text of the article.

  • The option of an exploratory IND (eIND) initiated by the US Food and Drug Administration enables first-in-human molecular imaging studies to be performed with reduced preclinical support as compared to that required for a full IND.

  • Consortia such as the Alzheimer's Disease Neuroimaging Initiative, the American College of Radiology Imaging Network and the High-Risk Plaque Initiative seek to correlate a number of imaging biomarkers with the clinical manifestations of diseases and, if successful, will greatly increase the inclusion of these imaging techniques in exploratory clinical development of novel therapeutics.

Abstract

Molecular imaging can allow the non-invasive assessment of biological and biochemical processes in living subjects. Such technologies therefore have the potential to enhance our understanding of disease and drug activity during preclinical and clinical drug development, which could aid decisions to select candidates that seem most likely to be successful or to halt the development of drugs that seem likely to ultimately fail. Here, with an emphasis on oncology, we review the applications of molecular imaging in drug development, highlighting successes and identifying key challenges that need to be addressed for successful integration of molecular imaging into the drug development process.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Molecular imaging and the drug development process.
Figure 2: A summary of modalities used for molecular imaging.
Figure 3: Complementation-based molecular imaging approach for studying drug-mediated protein–protein interactions in cell culture and in living animals.
Figure 4: High-throughput molecular imaging of oestrogen receptor–ligand interactions in vitro, in cell culture and in living subjects.
Figure 5: Molecular imaging of tumour characteristics.
Figure 6: A flow chart showing how different molecular imaging strategies can be integrated into different parts of the drug development pipeline.

Similar content being viewed by others

References

  1. DiMasi, J. A., Hansen, R. W. & Grabowski, H. G. The price of innovation: new estimates of drug development costs. J. Health Econ. 22, 151–185 (2003). Gives a cost estimation for development of future drugs.

    Article  PubMed  Google Scholar 

  2. Lindsay, M. A. Target discovery. Nature Rev. Drug Discov. 2, 831–838 (2003).

    Article  CAS  Google Scholar 

  3. Zambrowicz, B. P. & Sands, A. T. Knockouts model the 100 best-selling drugs — will they model the next 100? Nature Rev. Drug Discov. 2, 38–51 (2003).

    Article  CAS  Google Scholar 

  4. DiMasi, J. A., Hansen, R. W., Grabowski, H. G. & Lasagna, L. Cost of innovation in the pharmaceutical industry. J. Health Econ. 10, 107–142 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. Rudin, M. Imaging in Drug Discovery and Early Clinical Trials (Progress in Drug Research) Vol. 62 Foreword (Birkhauser, Switzerland, 2005).

    Google Scholar 

  6. Massoud, T. F. & Gambhir, S. S. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 17, 545–580 (2003). A detailed review on molecular imaging strategies.

    Article  CAS  PubMed  Google Scholar 

  7. Sosnovik, D. & Weissleder, R. Magnetic resonance and fluorescence based molecular imaging technologies. Prog. Drug Res. 62, 83–115 (2005).

    Article  PubMed  Google Scholar 

  8. Hildebrandt, I. J. & Gambhir, S. S. Molecular imaging applications for immunology. Clin. Immunol. 111, 210–224 (2004).

    Article  CAS  PubMed  Google Scholar 

  9. Min, J. J. & Gambhir, S. S. Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects. Gene Ther. 11, 115–125 (2004).

    Article  CAS  PubMed  Google Scholar 

  10. Penuelas, I., Haberkorn, U., Yaghoubi, S. & Gambhir, S. S. Gene therapy imaging in patients for oncological applications. Eur. J. Nucl. Med. Mol. Imaging 32 (Suppl. 2), 384–403 (2005).

    Article  Google Scholar 

  11. Ray, P. et al. Monitoring gene therapy with reporter gene imaging. Semin. Nucl. Med. 31, 312–320 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Schipper, M., Gambhir, S. S. in Diagnostic Nuclear Medicine (ed. Schiepers, C.) 313–342 (Springer, Berlin, Heidelberg, 2006).

    Book  Google Scholar 

  13. Kung, A. L. et al. Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell 6, 33–43 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Wang, W. & El-Deiry, W. S. Bioluminescent molecular imaging of endogenous and exogenous p53-mediated transcription in vitro and in vivo using an HCT116 human colon carcinoma xenograft model. Cancer Biol. Ther. 2, 196–202 (2003).

    Article  PubMed  Google Scholar 

  15. Wang, W. et al. Acridine derivatives activate p53 and induce tumor cell death through Bax. Cancer Biol. Ther. 4, 893–898 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Luker, K. E. & Piwnica-Worms, D. Optimizing luciferase protein fragment complementation for bioluminescent imaging of protein-protein interactions in live cells and animals. Methods Enzymol. 385, 349–360 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Massoud, T. F., Paulmurugan, R., De, A., Ray, P. & Gambhir, S. S. Reporter gene imaging of protein–protein interactions in living subjects. Curr. Opin. Biotechnol. 18, 31–37 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Massoud, T. F., Paulmurugan, R. & Gambhir, S. S. Molecular imaging of homodimeric protein–protein interactions in living subjects. FASEB J. 18, 1105–1107 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Paulmurugan, R. & Gambhir, S. S. Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein–protein interactions in cells and living animals. Cancer Res. 65, 7413–7420 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Paulmurugan, R. & Gambhir, S. S. An intramolecular folding sensor for imaging estrogen receptor–ligand interactions. Proc. Natl Acad. Sci. USA 103, 15883–15888 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Paulmurugan, R. & Gambhir, S. S. Combinatorial library screening for developing an improved split-firefly luciferase fragment-assisted complementation system for studying protein–protein interactions. Anal. Chem. 79, 2346–2353 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Paulmurugan, R., Massoud, T. F., Huang, J. & Gambhir, S. S. Molecular imaging of drug-modulated protein–protein interactions in living subjects. Cancer Res. 64, 2113–2119 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Paulmurugan, R., Ray, P., De, A., Chan, C. T. & Gambhir, S. S. in Protein–Protein Interactions: A Molecular Cloning Manual (eds Golemis, E. & Adams, P. D.) 695–713 (Cold Spring Harbor Laboratory Press, New York, 2005).

    Google Scholar 

  24. Paulmurugan, R., Ray, P., De, A., Chan, C. T. & Gambhir, S. S. Imaging protein–protein interactions in living subjects. Trends Analyt. Chem. 24, 446–458 (2005).

    Article  CAS  Google Scholar 

  25. Paulmurugan, R., Umezawa, Y. & Gambhir, S. S. Noninvasive imaging of protein–protein interactions in living subjects by using reporter protein complementation and reconstitution strategies. Proc. Natl Acad. Sci. USA 99, 15608–15613 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Luker, G. D., Sharma, V. & Piwnica-Worms, D. Visualizing protein–protein interactions in living animals. Methods 29, 110–122 (2003).

    Article  CAS  PubMed  Google Scholar 

  27. Villalobos, V., Naik, S. & Piwnica-Worms, D. Current state of imaging protein–protein interactions in vivo with genetically encoded reporters. Annu. Rev. Biomed. Eng. 9, 321–349 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Chan, C. T. et al. Molecular imaging of the efficacy of heat shock protein 90 inhibitors in living subjects. Cancer Res. 68, 216–226 (2008). A study on the use of molecular imaging for screening drug efficacy.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Forster, T. Zwischenmolekulare energiewanderung und fluoreszenz. Ann. Phys. 2, 54–75 (1948) (in German).

    Google Scholar 

  30. De, A. & Gambhir, S. S. Noninvasive imaging of protein–protein interactions from live cells and living subjects using bioluminescence resonance energy transfer. FASEB J. 19, 2017–2019 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. De, A., Loening, A. M. & Gambhir, S. S. An improved bioluminescence resonance energy transfer strategy for imaging intracellular events in single cells and living subjects. Cancer Res. 67, 7175–7183 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).

    CAS  PubMed  Google Scholar 

  33. Gambhir, S. S. Molecular imaging of cancer with positron emission tomography. Nature Rev. Cancer 2, 683–693 (2002).

    Article  CAS  Google Scholar 

  34. Warburg, O., Posener, K. & Negelein, E. Ueber den stoffwechsel der tumoren. Biochemische Zeitschrift 152, 319–344 (1924) (in German).

    Google Scholar 

  35. Gambhir, S. S. et al. A tabulated summary of the FDG PET literature. J. Nucl. Med. 42, 1S–93S (2001).

    CAS  PubMed  Google Scholar 

  36. Czernin, J. & Phelps, M. E. Positron emission tomography scanning: current and future applications. Annu. Rev. Med. 53, 89–112 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Czernin, J., Allen-Auerbach, M. & Schelbert, H. R. Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. J. Nucl. Med. 48 (Suppl. 1), 78–88 (2007).

    Google Scholar 

  38. Van den Abbeele, A. D. & Badawi, R. D. Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs). Eur. J. Cancer 38 (Suppl. 5), 60–65 (2002). A study on the use of FDG–PET in humans for early assessment of therapeutic effects of the drug imatinib mesylate.

    Article  Google Scholar 

  39. Bombardieri, E. The added value of metabolic imaging with FDG–PET in oesophageal cancer: prognostic role and prediction of response to treatment. Eur. J. Nucl. Med. Mol. Imaging 33, 753–758 (2006).

    Article  PubMed  Google Scholar 

  40. Kramer, H., Post, W. J., Pruim, J. & Groen, H. J. The prognostic value of positron emission tomography in non-small cell lung cancer: analysis of 266 cases. Lung Cancer 52, 213–217 (2006).

    Article  PubMed  Google Scholar 

  41. Hawkins, D. S. et al. [18F]Fluorodeoxyglucose positron emission tomography predicts outcome for Ewing sarcoma family of tumors. J. Clin. Oncol. 23, 8828–8834 (2005).

    Article  PubMed  Google Scholar 

  42. Hoekstra, C. J. et al. Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer. J. Clin. Oncol. 23, 8362–8370 (2005).

    Article  PubMed  Google Scholar 

  43. Xue, F. et al. F-18 fluorodeoxyglucose uptake in primary cervical cancer as an indicator of prognosis after radiation therapy. Gynecol. Oncol. 101, 147–151 (2006).

    Article  CAS  PubMed  Google Scholar 

  44. Kieninger, A. N., Welsh, R., Bendick, P. J., Zelenock, G. & Chmielewski, G. W. Positron-emission tomography as a prognostic tool for early-stage lung cancer. Am. J. Surg. 191, 433–436 (2006).

    Article  PubMed  Google Scholar 

  45. Svoboda, J. et al. Prognostic value of FDG–PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transplant 38, 211–216 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Eschmann, S. M. et al. 18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer. Eur. J. Nucl. Med. Mol. Imaging 34, 463–471 (2007).

    Article  PubMed  Google Scholar 

  47. Hutchings, M. et al. FDG–PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood 107, 52–59 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Kostakoglu, L. et al. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J. Nucl. Med. 43, 1018–1027 (2002).

    PubMed  Google Scholar 

  49. Levine, E. A. et al. Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG–PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer. Ann. Surg. 243, 472–478 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Mikhaeel, N. G., Hutchings, M., Fields, P. A., O'Doherty, M. J. & Timothy, A. R. FDG–PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma. Ann. Oncol. 16, 1514–1523 (2005).

    Article  CAS  PubMed  Google Scholar 

  51. Spaepen, K. et al. Early restaging positron emission tomography with 18F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann. Oncol. 13, 1356–1363 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Veit, P. et al. Detection of residual tumor after radiofrequency ablation of liver metastasis with dual-modality PET/CT: initial results. Eur. Radiol. 16, 80–87 (2006).

    Article  PubMed  Google Scholar 

  53. Ware, R. E. et al. Usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with a residual structural abnormality after definitive treatment for squamous cell carcinoma of the head and neck. Head Neck 26, 1008–1017 (2004).

    Article  PubMed  Google Scholar 

  54. Dehdashti, F. et al. Positron emission tomographic assessment of “metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy. Eur. J. Nucl. Med. 26, 51–56 (1999).

    Article  CAS  PubMed  Google Scholar 

  55. Prenen, H. et al. Imatinib mesylate inhibits glucose uptake in gastrointestinal stromal tumor cells by downregulation of the glucose transporters recruitment to the plasma membrane. Am. J. Biochem. Biotechnol. 1, 95–102 (2005).

    Article  CAS  Google Scholar 

  56. Isselbacher, K. J. Sugar and amino acid transport by cells in culture — differences between normal and malignant cells. N. Engl. J. Med. 286, 929–933 (1972).

    Article  CAS  PubMed  Google Scholar 

  57. Jager, P. L. et al. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J. Nucl. Med. 42, 432–445 (2001).

    CAS  PubMed  Google Scholar 

  58. Oka, S. et al. A preliminary study of anti-1-amino-3-18F-fluorocyclobutyl-1-carboxylic acid for the detection of prostate cancer. J. Nucl. Med. 48, 46–55 (2007).

    CAS  PubMed  Google Scholar 

  59. Schuster, D. M. et al. Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. J. Nucl. Med. 48, 56–63 (2007).

    CAS  PubMed  Google Scholar 

  60. Katz-Brull, R., Seger, D., Rivenson-Segal, D., Rushkin, E. & Degani, H. Metabolic markers of breast cancer: enhanced choline metabolism and reduced choline-ether-phospholipid synthesis. Cancer Res. 62, 1966–1970 (2002).

    CAS  PubMed  Google Scholar 

  61. Liu, D. et al. Use of radiolabelled choline as a pharmacodynamic marker for the signal transduction inhibitor geldanamycin. Br. J. Cancer 87, 783–789 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kelloff, G. J. et al. The progress and promise of molecular imaging probes in oncologic drug development. Clin. Cancer Res. 11, 7967–7985 (2005).

    Article  CAS  PubMed  Google Scholar 

  63. Tseng, J. R. et al. Reproducibility of 3′-deoxy-3′-18F-fluorothymidine microPET studies in tumor xenografts in mice. J. Nucl. Med. 46, 1851–1857 (2005).

    CAS  PubMed  Google Scholar 

  64. Leyton, J. et al. 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, 4202–4210 (2005).

    Article  CAS  PubMed  Google Scholar 

  65. Buck, A. K. et al. 3-deoxy-3-[18F]fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res. 62, 3331–3334 (2002).

    CAS  PubMed  Google Scholar 

  66. Vesselle, H. et al. In vivo validation of 3′deoxy-3′-[18F]fluorothymidine ([18F]FLT) as a proliferation imaging tracer in humans: correlation of [18F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin. Cancer Res. 8, 3315–3323 (2002).

    CAS  PubMed  Google Scholar 

  67. Perumal, M. et al. Redistribution of nucleoside transporters to the cell membrane provides a novel approach for imaging thymidylate synthase inhibition by positron emission tomography. Cancer Res. 66, 8558–8564 (2006).

    Article  CAS  PubMed  Google Scholar 

  68. Blasberg, R. G. et al. Imaging brain tumor proliferative activity with [124I]iododeoxyuridine. Cancer Res. 60, 624–635 (2000).

    CAS  PubMed  Google Scholar 

  69. Sun, H. et al. Imaging DNA synthesis in vivo with 18F-FMAU and PET. J. Nucl. Med. 46, 292–296 (2005).

    CAS  PubMed  Google Scholar 

  70. Kenny, L. M., Aboagye, E. O. & Price, P. M. Positron emission tomography imaging of cell proliferation in oncology. Clin. Oncol. (R. Coll. Radiol.) 16, 176–185 (2004).

    Article  CAS  Google Scholar 

  71. Mankoff, D. A., Shields, A. F. & Krohn, K. A. PET imaging of cellular proliferation. Radiol. Clin. North Am. 43, 153–167 (2005).

    Article  PubMed  Google Scholar 

  72. Hajra, K. M. & Liu, J. R. Apoptosome dysfunction in human cancer. Apoptosis 9, 691–704 (2004).

    Article  CAS  PubMed  Google Scholar 

  73. Hersey, P. & Zhang, X. D. Overcoming resistance of cancer cells to apoptosis. J. Cell Physiol. 196, 9–18 (2003).

    Article  CAS  PubMed  Google Scholar 

  74. Blankenberg, F. G. et al. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc. Natl Acad. Sci. USA 95, 6349–6354 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Blankenberg, F. G. et al. Imaging of apoptosis (programmed cell death) with 99mTc annexin V. J. Nucl. Med. 40, 184–191 (1999).

    CAS  PubMed  Google Scholar 

  76. Glaser, M. et al. Iodine-124 labelled annexin-V as a potential radiotracer to study apoptosis using positron emission tomography. Appl. Radiat. Isot. 58, 55–62 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Grierson, J. R. et al. Production of [F-18]fluoroannexin for imaging apoptosis with PET. Bioconjug. Chem. 15, 373–379 (2004).

    Article  CAS  PubMed  Google Scholar 

  78. Belhocine, T., Steinmetz, N., Green, A. & Rigo, P. In vivo imaging of chemotherapy-induced apoptosis in human cancers. Ann. NY Acad. Sci. 1010, 525–529 (2003).

    Article  CAS  PubMed  Google Scholar 

  79. Belhocine, T. et al. Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin. Cancer Res. 8, 2766–2774 (2002).

    CAS  PubMed  Google Scholar 

  80. Boersma, H. H. et al. Past, present, and future of annexin A5: from protein discovery to clinical applications. J. Nucl. Med. 46, 2035–2050 (2005).

    CAS  PubMed  Google Scholar 

  81. Corsten, M. F., Hofstra, L., Narula, J. & Reutelingsperger, C. P. Counting heads in the war against cancer: defining the role of annexin A5 imaging in cancer treatment and surveillance. Cancer Res. 66, 1255–1260 (2006).

    Article  CAS  PubMed  Google Scholar 

  82. Blankenberg, F. G., Backer, M. V., Levashova, Z., Patel, V. & Backer, J. M. In vivo tumor angiogenesis imaging with site-specific labeled (99m)Tc-HYNIC-VEGF. Eur. J. Nucl. Med. Mol. Imaging 33, 841–848 (2006).

    Article  PubMed  Google Scholar 

  83. Haubner, R. αvβ3-integrin imaging: a new approach to characterise angiogenesis? Eur. J. Nucl. Med. Mol. Imaging 33 (Suppl. 13), 54–63 (2006).

    Article  CAS  PubMed  Google Scholar 

  84. Haubner, R. et al. Radiolabeled αvβ3 integrin antagonists: a new class of tracers for tumor targeting. J. Nucl. Med. 40, 1061–1071 (1999).

    CAS  PubMed  Google Scholar 

  85. Chen, X., Conti, P. S. & Moats, R. A. In vivo near-infrared fluorescence imaging of integrin αvβ3 in brain tumor xenografts. Cancer Res. 64, 8009–8014 (2004).

    Article  CAS  PubMed  Google Scholar 

  86. Haubner, R. et al. Noninvasive imaging of αvβ3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res. 61, 1781–1785 (2001).

    CAS  PubMed  Google Scholar 

  87. Janssen, M. L. et al. Tumor targeting with radiolabeled αvβ3 integrin binding peptides in a nude mouse model. Cancer Res. 62, 6146–6151 (2002).

    CAS  PubMed  Google Scholar 

  88. van Hagen, P. M. et al. Evaluation of a radiolabelled cyclic DTPA-RGD analogue for tumour imaging and radionuclide therapy. Int. J. Cancer 90, 186–198 (2000).

    Article  CAS  PubMed  Google Scholar 

  89. Beer, A. J. et al. Comparison of integrin αvβ3 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, 22–29 (2008). A study on translation of angiogenesis imaging with PET to humans.

    Article  PubMed  Google Scholar 

  90. Beer, A. J. et al. Patterns of αvβ3 expression in primary and metastatic human breast cancer as shown by 18F-Galacto-RGD PET. J. Nucl. Med. 49, 255–259 (2008).

    Article  PubMed  Google Scholar 

  91. Haubner, R. et al. Noninvasive visualization of the activated αvβ3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD. PLoS Med. 2, e70 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Zhang, X. et al. Quantitative pet imaging of tumor integrin αvβ3 expression with 18F-FRGD2. J. Nucl. Med. 47, 113–121 (2006).

    CAS  PubMed  Google Scholar 

  93. Cai, W. et al. In vitro and in vivo characterization of 64Cu-labeled Abegrin, a humanized monoclonal antibody against integrin αvβ3 . Cancer Res. 66, 9673–9681 (2006).

    Article  CAS  PubMed  Google Scholar 

  94. Cai, W. et al. Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. Nano Lett. 6, 669–676 (2006).

    Article  CAS  PubMed  Google Scholar 

  95. Ellegala, D. B. et al. Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to αvβ3 . Circulation 108, 336–341 (2003). A proof-of-principle study on ultrasonic tumour angiogenesis imaging using microbubbles targeted to α v β 3 integrin.

    Article  PubMed  Google Scholar 

  96. Korpanty, G., Carbon, J. G., Grayburn, P. A., Fleming, J. B. & Brekken, R. A. Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clin. Cancer Res. 13, 323–330 (2007).

    Article  CAS  PubMed  Google Scholar 

  97. Willmann, J. K. et al. US imaging of tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice. Radiology 246, 508–518 (2008).

    Article  PubMed  Google Scholar 

  98. Willmann, J. K. et al. Targeted microbubbles for imaging tumor angiogenesis: assessment of whole-body biodistribution with dynamic MicroPET imaging in mice. Radiology (in the press).

  99. Willmann, J. K. et al. Dual-targeted contrast agent for ultrasonic assessment of tumor angiogenesis in vivo. Radiology (in the press).

  100. Bremer, C., Bredow, S., Mahmood, U., Weissleder, R. & Tung, C. H. Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model. Radiology 221, 523–529 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Cai, W., Rao, J., Gambhir, S. S. & Chen, X. How molecular imaging is speeding up antiangiogenic drug development. Mol. Cancer Ther. 5, 2624–2633 (2006).

    Article  CAS  PubMed  Google Scholar 

  102. Rehman, S. & Jayson, G. C. Molecular imaging of antiangiogenic agents. Oncologist 10, 92–103 (2005).

    Article  CAS  PubMed  Google Scholar 

  103. Rasey, J. S. et al. Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int. J. Radiat. Oncol. Biol. Phys. 36, 417–428 (1996).

    Article  CAS  PubMed  Google Scholar 

  104. Koh, W. J. et al. Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. Int. J. Radiat. Oncol. Biol. Phys. 33, 391–398 (1995).

    Article  CAS  PubMed  Google Scholar 

  105. Koh, W. J. et al. Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. Int. J. Radiat. Oncol. Biol. Phys. 22, 199–212 (1992).

    Article  CAS  PubMed  Google Scholar 

  106. Dehdashti, F. et al. 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, 1233–1238 (2003).

    Article  PubMed  Google Scholar 

  107. Dehdashti, F. et al. In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM. Eur. J. Nucl. Med. Mol. Imaging 30, 844–850 (2003).

    Article  CAS  PubMed  Google Scholar 

  108. Solomon, B. et al. Modulation of intratumoral hypoxia by the epidermal growth factor receptor inhibitor gefitinib detected using small animal PET imaging. Mol. Cancer Ther. 4, 1417–1422 (2005).

    Article  CAS  PubMed  Google Scholar 

  109. Foo, S. S., Abbott, D. F., Lawrentschuk, N. & Scott, A. M. Functional imaging of intratumoral hypoxia. Mol. Imaging Biol. 6, 291–305 (2004).

    Article  PubMed  Google Scholar 

  110. Rajendran, J. G. & Krohn, K. A. Imaging hypoxia and angiogenesis in tumors. Radiol. Clin. North Am. 43, 169–187 (2005).

    Article  PubMed  Google Scholar 

  111. Dimasi, J. A. Risks in new drug development: approval success rates for investigational drugs. Clin. Pharmacol. Ther. 69, 297–307 (2001).

    Article  CAS  PubMed  Google Scholar 

  112. Rudin, M. & Weissleder, R. Molecular imaging in drug discovery and development. Nature Rev. Drug Discov. 2, 123–131 (2003).

    Article  CAS  Google Scholar 

  113. Fischman, A. J., Alpert, N. M. & Rubin, R. H. Pharmacokinetic imaging: a noninvasive method for determining drug distribution and action. Clin. Pharmacokinet. 41, 581–602 (2002). A review on the use of imaging for assessing of drug pharmacokinetics.

    Article  CAS  PubMed  Google Scholar 

  114. Berridge, M. S. & Heald, D. L. In vivo characterization of inhaled pharmaceuticals using quantitative positron emission tomography. J. Clin. Pharmacol. (Suppl.), 25S–29S (1999).

  115. Farde, L. et al. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch. Gen. Psychiatry 49, 538–544 (1992).

    Article  CAS  PubMed  Google Scholar 

  116. Farde, L., Wiesel, F. A., Nordstrom, A. L. & Sedvall, G. D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology (Berl.) 99 (Suppl.), S28–S31 (1989).

    Article  Google Scholar 

  117. Bench, C. J. et al. The time course of binding to striatal dopamine D2 receptors by the neuroleptic ziprasidone (CP-88,059-001) determined by positron emission tomography. Psychopharmacology (Berl.) 124, 141–147 (1996).

    Article  CAS  Google Scholar 

  118. Hode, Y. et al. A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian). Psychopharmacology (Berl.) 180, 377–384 (2005).

    Article  CAS  Google Scholar 

  119. Farde, L. The advantage of using positron emission tomography in drug research. Trends Neurosci. 19, 211–214 (1996).

    Article  CAS  PubMed  Google Scholar 

  120. Wilding, I. R. & Bell, J. A. Improved early clinical development through human microdosing studies. Drug Discov. Today 10, 890–894 (2005).

    Article  PubMed  Google Scholar 

  121. Saleem, A. et al. Pharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in patients by positron emission tomography. J. Clin. Oncol. 19, 1421–1429 (2001).

    Article  CAS  PubMed  Google Scholar 

  122. Saleem, A. et al. Metabolic activation of temozolomide measured in vivo using positron emission tomography. Cancer Res. 63, 2409–2415 (2003).

    CAS  PubMed  Google Scholar 

  123. Saleem, A., Charnley, N. & Price, P. Clinical molecular imaging with positron emission tomography. Eur. J. Cancer 42, 1720–1727 (2006).

    Article  CAS  PubMed  Google Scholar 

  124. Garner, R. C. Less is more: the human microdosing concept. Drug Discov. Today 10, 449–451 (2005).

    Article  PubMed  Google Scholar 

  125. Gambhir, S. S. in PET: Molecular Imaging and Its Biological Applications (ed. Phelps, M. E.) 125–216 (Springer, New York, 2004).

    Book  Google Scholar 

  126. Lesko, L. J. & Atkinson, A. J. Jr. Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu. Rev. Pharmacol. Toxicol. 41, 347–366 (2001).

    Article  CAS  PubMed  Google Scholar 

  127. Richter, W. S. Imaging biomarkers as surrogate endpoints for drug development. Eur. J. Nucl. Med. Mol. Imaging 33, 6–10 (2006).

    Article  PubMed  Google Scholar 

  128. Smith, J. J., Sorensen, A. G. & Thrall, J. H. Biomarkers in imaging: realizing radiology's future. Radiology 227, 633–638 (2003). A useful review on imaging biomarkers.

    Article  PubMed  Google Scholar 

  129. Pien, H. H., Fischman, A. J., Thrall, J. H. & Sorensen, A. G. Using imaging biomarkers to accelerate drug development and clinical trials. Drug Discov. Today 10, 259–266 (2005).

    Article  CAS  PubMed  Google Scholar 

  130. Wang, Y. X. Medical imaging in pharmaceutical clinical trials: what radiologists should know. Clin. Radiol. 60, 1051–1057 (2005).

    Article  PubMed  Google Scholar 

  131. Beer, A. J. et al. Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients. J. Nucl. Med. 46, 1333–1341 (2005).

    CAS  PubMed  Google Scholar 

  132. Weber, W. A. Positron emission tomography as an imaging biomarker. J. Clin. Oncol. 24, 3282–3292 (2006).

    Article  CAS  PubMed  Google Scholar 

  133. Katz, R. Biomarkers and surrogate markers: an FDA perspective. NeuroRx 1, 189–195 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Jung, J. C. & Schnitzer, M. J. Multiphoton endoscopy. Opt. Lett. 28, 902–904 (2003).

    Article  PubMed  Google Scholar 

  135. Rudin, M., Rausch, M. & Stoeckli, M. Molecular imaging in drug discovery and development: potential and limitations of nonnuclear methods. Mol. Imaging Biol. 7, 5–13 (2005).

    Article  PubMed  Google Scholar 

  136. Schmidt, M. E. The future of imaging in drug discovery. J. Clin. Pharmacol. (Suppl), 45S–50S (1999).

  137. Dimasi, J. A. New drug development in the United States from 1963 to 1999. Clin. Pharmacol. Ther. 69, 286–296 (2001).

    Article  CAS  PubMed  Google Scholar 

  138. Ginos, J. Z. et al. [13N]cisplatin PET to assess pharmacokinetics of intra-arterial versus intravenous chemotherapy for malignant brain tumors. J. Nucl. Med. 28, 1844–1852 (1987).

    CAS  PubMed  Google Scholar 

  139. Kissel, J. et al. Pharmacokinetic analysis of 5-[18F]fluorouracil tissue concentrations measured with positron emission tomography in patients with liver metastases from colorectal adenocarcinoma. Cancer Res. 57, 3415–3423 (1997).

    CAS  PubMed  Google Scholar 

  140. Inoue, T. et al. Positron emission tomography using [18F]fluorotamoxifen to evaluate therapeutic responses in patients with breast cancer: preliminary study. Cancer Biother. Radiopharm. 11, 235–245 (1996).

    Article  CAS  PubMed  Google Scholar 

  141. Jayson, G. C. et al. Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. J. Natl Cancer Inst. 94, 1484–1493 (2002).

    Article  CAS  PubMed  Google Scholar 

  142. Su, H. et al. Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors. Clin. Cancer Res. 12, 5659–5667 (2006).

    Article  CAS  PubMed  Google Scholar 

  143. Mankoff, D. A. et al. Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy. J. Nucl. Med. 44, 1806–1814 (2003).

    PubMed  Google Scholar 

  144. Anderson, H. L. et al. Assessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate. J. Clin. Oncol. 21, 2823–2830 (2003).

    Article  CAS  PubMed  Google Scholar 

  145. Jacobs, A. et al. Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 358, 727–729 (2001).

    Article  CAS  PubMed  Google Scholar 

  146. Kim, Y. R. et al. Detection of early antiangiogenic effects in human colon adenocarcinoma xenografts: in vivo changes of tumor blood volume in response to experimental VEGFR tyrosine kinase inhibitor. Cancer Res. 65, 9253–9260 (2005).

    Article  CAS  PubMed  Google Scholar 

  147. Barentsz, J. O. et al. Evaluation of chemotherapy in advanced urinary bladder cancer with fast dynamic contrast-enhanced MR imaging. Radiology 207, 791–797 (1998).

    Article  CAS  PubMed  Google Scholar 

  148. Morgan, B. et al. 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, 3955–3964 (2003).

    Article  CAS  PubMed  Google Scholar 

  149. Robinson, S. P. et al. Tumour dose response to the antivascular agent ZD6126 assessed by magnetic resonance imaging. Br. J. Cancer 88, 1592–1597 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Stevenson, J. P. et al. 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, 4428–4438 (2003).

    Article  CAS  PubMed  Google Scholar 

  151. Thomas, J. P. et al. Phase I pharmacokinetic and pharmacodynamic study of recombinant human endostatin in patients with advanced solid tumors. J. Clin. Oncol. 21, 223–231 (2003).

    Article  CAS  PubMed  Google Scholar 

  152. Galbraith, S. M. et al. Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging. J. Clin. Oncol. 21, 2831–2842 (2003).

    Article  CAS  PubMed  Google Scholar 

  153. Wolf, W., Waluch, V. & Presant, C. A. Non-invasive 19F-NMRS of 5-fluorouracil in pharmacokinetics and pharmacodynamic studies. NMR Biomed. 11, 380–387 (1998).

    Article  CAS  PubMed  Google Scholar 

  154. Blackstock, A. W. et al. Tumor uptake and elimination of 2′, 2′-difluoro-2′-deoxycytidine (gemcitabine) after deoxycytidine kinase gene transfer: correlation with in vivo tumor response. Clin. Cancer Res. 7, 3263–3268 (2001).

    CAS  PubMed  Google Scholar 

  155. Rodrigues, L. M. et al. In vivo detection of ifosfamide by 31P-MRS in rat tumours: increased uptake and cytotoxicity induced by carbogen breathing in GH3 prolactinomas. Br. J. Cancer 75, 62–68 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Abdollahi, A. et al. Combined therapy with direct and indirect angiogenesis inhibition results in enhanced antiangiogenic and antitumor effects. Cancer Res. 63, 8890–8898 (2003).

    CAS  PubMed  Google Scholar 

  157. Goertz, D. E., Yu, J. L., Kerbel, R. S., Burns, P. N. & Foster, F. S. High-frequency Doppler ultrasound monitors the effects of antivascular therapy on tumor blood flow. Cancer Res. 62, 6371–6375 (2002).

    CAS  PubMed  Google Scholar 

  158. Iordanescu, I., Becker, C., Zetter, B., Dunning, P. & Taylor, G. A. Tumor vascularity: evaluation in a murine model with contrast-enhanced color Doppler US effect of angiogenesis inhibitors. Radiology 222, 460–467 (2002).

    Article  PubMed  Google Scholar 

  159. Franco, M. et al. Targeted anti-vascular endothelial growth factor receptor-2 therapy leads to short-term and long-term impairment of vascular function and increase in tumor hypoxia. Cancer Res. 66, 3639–3648 (2006).

    Article  CAS  PubMed  Google Scholar 

  160. Bertolotto, M. et al. Blood flow changes in hepatocellular carcinoma after the administration of thalidomide assessed by reperfusion kinetics during microbubble infusion: preliminary results. Invest. Radiol. 41, 15–21 (2006).

    Article  CAS  PubMed  Google Scholar 

  161. Hsu, C. et al. Effect of thalidomide in hepatocellular carcinoma: assessment with power doppler US and analysis of circulating angiogenic factors. Radiology 235, 509–516 (2005).

    Article  PubMed  Google Scholar 

  162. Niermann, K. J. et al. Sonographic depiction of changes of tumor vascularity in response to various therapies. Ultrasound Q. 21, 61–67; quiz 149, 153–154 (2005).

    PubMed  Google Scholar 

  163. Gee, M. S. et al. Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations. Cancer Res. 61, 2974–2982 (2001).

    CAS  PubMed  Google Scholar 

  164. Unger, E. C., McCreery, T. P., Sweitzer, R. H., Caldwell, V. E. & Wu, Y. Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent. Invest. Radiol. 33, 886–892 (1998).

    Article  CAS  PubMed  Google Scholar 

  165. Krix, M. et al. Sensitive noninvasive monitoring of tumor perfusion during antiangiogenic therapy by intermittent bolus-contrast power Doppler sonography. Cancer Res. 63, 8264–8270 (2003).

    CAS  PubMed  Google Scholar 

  166. Shah, K., Tang, Y., Breakefield, X. & Weissleder, R. Real-time imaging of TRAIL-induced apoptosis of glioma tumors in vivo. Oncogene 22, 6865–6872 (2003).

    Article  CAS  PubMed  Google Scholar 

  167. Bremer, C., Tung, C. H. & Weissleder, R. In vivo molecular target assessment of matrix metalloproteinase inhibition. Nature Med. 7, 743–748 (2001). A study on optical imaging using an activatable reporter probe.

    Article  CAS  PubMed  Google Scholar 

  168. Rehemtulla, A. et al. Molecular imaging of gene expression and efficacy following adenoviral-mediated brain tumor gene therapy. Mol. Imaging 1, 43–55 (2002).

    Article  CAS  PubMed  Google Scholar 

  169. Laxman, B. et al. Noninvasive real-time imaging of apoptosis. Proc. Natl Acad. Sci. USA 99, 16551–16555 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Ntziachristos, V. et al. Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate. Proc. Natl Acad. Sci. USA 101, 12294–12299 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Montet, X., Ntziachristos, V., Grimm, J. & Weissleder, R. Tomographic fluorescence mapping of tumor targets. Cancer Res. 65, 6330–6336 (2005).

    Article  CAS  PubMed  Google Scholar 

  172. Wu, K. D. et al. Investigation of antitumor effects of synthetic epothilone analogs in human myeloma models in vitro and in vivo. Proc. Natl Acad. Sci. USA 102, 10640–10645 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Lamfers, M. L. et al. Cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging. Mol. Ther. 14, 779–788 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the support of the Swiss Foundation of Medical-Biological Grants (J.K.W.), the Novartis Research Foundation (J.K.W.), the Swiss Society of Radiology (J.K.W.), as well as the support of NIH grants ICMIC CA114747 P50 (S.S.G.), CCNE U54 CA 119367 (S.S.G.), R01 CA082214 (S.S.G.), R01 HL078632 (S.S.G.), Doris Duke Foundation (S.S.G.), and the Canary Foundation (S.S.G.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sanjiv S. Gambhir.

Ethics declarations

Competing interests

S.S.G. is on the advisory board for Centella, Chiron, CTI/PetMet Pharmaceutical Inc., Endra, Enlight, Genetech, General Electric, GlaxoSmithKline, Henry Ford Health Systems, Lumen Therapeutics, MediGene Inc., Philips Medical Systems, Plexera, Varian Medical Inc., VisualSonics. He has served as a consultant for MediGene Inc., Millennium, Philips Medical Systems and Spectrum Dynamics. He has received grants from Alza, Bayer Schering, the Department of Energy, General Electric. He has had industrial research collaboration with GlaxoSmithKline, Nova R&D, Pfizer, RMD Inc. He has stocks with Endra, Enlight, Pfizer, Spectrum Dynamics, VisualSonics, and received honorarium from Siemens. N.V.B. is affiliated (employee) with Genentech. This manuscript refers to some Genentech products. L.M.D. is an employee of Bayer Schering Pharma.

Supplementary information

Supplementary information S1 (box)

A summary of imaging modalities (PDF 155 kb)

Related links

Related links

FURTHER INFORMATION

Alzheimer's Disease Neuroimaging Initiative

American College of Radiology Imaging Network

Guidance for Industry, Investigators, and Reviewers Exploratory IND Studies

High-Risk Plaque Initiative

Molecular Imaging and Contrast Agent Database

Glossary

Investigational new drug application

Before initiating any clinical trials of a new drug in humans in the United States, a drug sponsor must submit an investigational new drug application (IND) to the US FDA. The IND contains three broad categories of information: data from animal pharmacology and toxicology studies, manufacturing information, and clinical protocols and investigator information.

Tumour xenograft

Tumour specimens can be grown in immunocompromised rodents to provide tumour models with many of the complexities of human tumours.

Luciferase

The luciferase assay is a method to detect the presence of ATP based on the ability of the firefly enzyme luciferase to catalyse a reaction between its substrate luciferin and ATP, releasing the two terminal phosphate groups of ATP. Luciferin becomes excited during the process and, on return to its basal state, releases energy in the form of light.

Metabolic flare

Metabolic flare corresponds to an increase of radiotracer uptake (for example, FDG) in tissue (for example, in a tumour) following radiotherapy, hormonal therapy or chemotherapy. Possible causes for this phenomenon include post-therapeutic inflammatory reactions, increased energy utilization related to induction of apoptosis, or partial agonistic effects of hormonal therapy (for example, during anti-oestrogen therapy in breast cancer).

Bio-isosteric substitution

The substitution by a radiolabel of similar size, electronic configuration and lipophilicity for a portion of the parent drug molecule.

Pharmacophore

The steric and electronic features of a ligand that are necessary to ensure optimal interactions with a biological target structure and to trigger (or to block) its biological response.

Chelating agent

A molecule that has the capacity of tight metal binding (complexation).

Clinical end point

A clinical end point assesses how a patient feels, functions or survives.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Willmann, J., van Bruggen, N., Dinkelborg, L. et al. Molecular imaging in drug development. Nat Rev Drug Discov 7, 591–607 (2008). https://doi.org/10.1038/nrd2290

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrd2290

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing