The role of positron emission tomography in the discovery and development of new drugs; As studied in laboratory animals

  • Peter Roselt
  • Steven Meikle
  • Michael Kassiou
Review Article

Summary

Drug discovery and development is time consuming and a costly procedure. The challenges for the pharmaceutical industry range from the evaluation of potential new drug candidates, the determination of drug pharmacokinetics/pharmacodynamics, the measurement of receptor occupancy as a determinant of drug efficacy, and the pharmacological characterisation of mechanisms of action. Positron emission tomography (PET) is a powerful quantitative imaging technique for looking at biochemical pathways, molecular interactions, drug pharmacokinetics and pharmacodynamics. Recent advances in emission tomography, particularly the development of small animal PET scanners, image reconstruction and animal models of disease have led to the development of extremely sensitive and specific tools for imaging biochemical processes in vivo, therefore representing a new means of providing information for drug development and evaluation. Many human genes have a related mouse gene, allowing mice to be used as a platform for mimicking human disease, using knock-out and knock-in gene technology. Consequently PET imaging of rodents is emerging as a cost effective means of screening new pharmaceuticals and decreasing the time required for new drug development.

Keywords

Positron emission tomography drug development small animal imaging 

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References

  1. 1.
    Campbell, B. (1995) Drug development and positron emission tomography in PET for drug development and evaluation (Comar, D., ed) pp. 1–24, Kluwer Academic Publishers, Dordrecht.Google Scholar
  2. 2.
    Phelps, M. (2000): Positron emission tomography provides molecular imaging of biological processes., Proc. Natl. Acad. Sci. USA. 97, 9226–9233.CrossRefPubMedGoogle Scholar
  3. 3.
    Herschman, H. (2003): Molecular imaging: looking at problems, seeing solutions. Science. 302, 605–608.CrossRefPubMedGoogle Scholar
  4. 4.
    Czernin, J., & Phelps, M. (2002): Positron emission tomography scanning: current and future applications., Ann. Rev. Med., 53, 89–112.CrossRefPubMedGoogle Scholar
  5. 5.
    Buck, A., Schirrmeister, H., Hetzel, M., Von Der Heide, M., Halter, G., Mattfeldt, T., Liewald, F., Reske, S., & Neumaier, B. (2002): 3-Deoxy-3-[18F]fluorothymidine positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules., Cancer Res., 62, 3331–3334.PubMedGoogle Scholar
  6. 6.
    Vesselle, H., Grierson, J., Muzi, M., Pugsley, J., Schmidt, R., Rabinowitz, P., Peterson, L., Vallieres, E., & Wood, D. (2002): In vivo validation of 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lund tumours., Clin. Cancer Res., 8, 3315–23.PubMedGoogle Scholar
  7. 7.
    Halldin, C., Gulyas, B., & Farde, L. (2001): PET studies with carbon-11 radioligands in neuropsychopharmacological drug development., Curr. Pharm. Des., 7, 1907–1929.CrossRefPubMedGoogle Scholar
  8. 8.
    Maziere, B., & Loc’h, C. (2001): Using bromine-76 and iodine-123 radiohalogenated tracers in the drug development process., Curr. Pharm. Des., 7, 1931–1943.CrossRefPubMedGoogle Scholar
  9. 9.
    Brady, F., Luthra, S., Brown, G., Osam, S., Aboagye, E., Saleem, A. & Price, P. (2001): Radiolabelled tracers and anticancer drugs for assessment of therapeutic efficacy using PET., Curr. Pharm. Des., 7, 1863–1892.CrossRefPubMedGoogle Scholar
  10. 10.
    Hume, S. P., Brown, D., Ashworth, S., Hirani, E., Luthra, S. & Lammertsma, A. (1997): In vivo saturation kinetics of two dopamine transporter probes measured using a small animal scanner., J. Neurosci. Methods. 76, 45–51.CrossRefPubMedGoogle Scholar
  11. 11.
    Chatziioannou, A. F. (2002): Molecular imaging of small animals with dedicated PET tomographs, Eur J Nucl Med Mol Imaging. 29, 98–114.CrossRefPubMedGoogle Scholar
  12. 12.
    Myers, R., & Hume, S. P. (2002): Small animal PET, European Neuropsychopharmacology. 12, 545–555.CrossRefPubMedGoogle Scholar
  13. 13.
    Del Guerra, A., & Belcari, N. (2002): Advances in animal PET scanners, Q. J. Nucl. Med., 46, 35–47.PubMedGoogle Scholar
  14. 14.
    Cherry, S. (1994): Recent advances in instrumentation for positron emission tomography., Nucl. Instr. & Methods in Phys. Res A., 348, 577–582.CrossRefGoogle Scholar
  15. 15.
    Chatziioannou, A. F., Cherry, S., Shao, Y., Silverman, R., Meadors, K., Farquhar, T., Pedarsani, M., & Phelps, M. (1999): Performance evaluation of microPET: A high resolution lutetium oxyorthosilicate PET scanner for animal imaging., J. Nucl. Med., 40, 1164–1175.PubMedGoogle Scholar
  16. 16.
    DeJesus, O., Murali, D., Flores, L., Converse, A., Dick, D., Oaks, T., Roberts, A., & Nickles, R. (2003): Synthesis of [F-18]ZD1839 as a PET imaging agent for epidermal growth factor receptors., J. Labelled Comp. Radiopharm., 46, S1.CrossRefGoogle Scholar
  17. 17.
    Haubner, R., Wester, H., Weber, W., Mang, C., Ziegler, S., Goodman, S., Senekowitsch-Schmidtke, R., Kessler, H., & Schwaiger, M. (2001): Noninvasiveimaging of αvβ3 integrin expression using18F-labeled RGB-containing glycopeptide and positron emission tomography., Cancer Res., 61, 1781–1785.PubMedGoogle Scholar
  18. 18.
    Solomon, B., McArthur, G., Cuillinane, C., Zalcberg, J., & Hicks, R. (2003): Applications of positron emission tomography in the development of molecular targeted cancer therapeutics., Biodrugs. 17, 339–354.CrossRefPubMedGoogle Scholar
  19. 19.
    Wiebe, L., & Knaus, E. (2001): Enzyme-targeted, nucleoside-based radiopharmaceuticals for scintigraphic monitoring of gene transfer and expression., Curr. Pharm. Des., 7, 1893–1906.CrossRefPubMedGoogle Scholar
  20. 20.
    Phelps, M. (2000): PET: The merging of biology and imaging into molecular imaging., J. Nucl. Med., 41, 661–681.PubMedGoogle Scholar
  21. 21.
    Tjuvajev, J., Avril, N., Oku, T., Sasajima, T., Miyagawa, T., Joshi, R., Safer, M., Beattie, B., DiResta, G., Daghighian, F., Augensen, F., Koutcher, J., Zweit, J., Humm, J., Larson, S., Finn, R., & Blasberg, R. (1998): Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography, Cancer Res., 58, 4333–4341.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Peter Roselt
    • 1
  • Steven Meikle
    • 3
  • Michael Kassiou
    • 3
    • 2
  1. 1.Centre for Positron Emission TomographyPeter MacCallum Cancer CentreEast MelbourneAustralia
  2. 2.Department of PharmacologyUniversity of SydneyAustralia
  3. 3.Department of PET and Nuclear MedicineRoyal Prince Alfred HospitalCamperdownAustralia

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