PET Chemistry pp 317-327 | Cite as

Pharmacological Prerequisites for PET Ligands and Practical Issues in Preclinical PET Research

  • S. M. Ametamey
  • M. Honer
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 64)


The development of PET radiopharmaceuticals for the non-invasive imaging of cancerous lesions, brain receptors, transporters and enzymes started more than 25 years ago. But till today no established algorithms exist to predict the success of a PET radiopharmaceutical. PET radioligand development is a challenging endeavor and predicting the success of PET ligand can be an elusive undertaking. A large number of PET radiopharmaceuticals have been developed for imaging, but so far only a few have found application as imaging agents in vivo in humans. Typically, the potential compound selected for development usually has the desired in vitro characteristics but unknown in vivo properties. The purpose of this chapter is to highlight some of the pharmacological constraints and prerequisites. Interspecies difference in metabolism and mass effects are discussed with examples. Finally, some of the practical issues related to laboratory animal imaging using anesthetic agents are also presented.


Positron Emission Tomography Positron Emission Tomography Study Positron Emission Tomography Tracer Small Animal Positron Emission Tomography Positron Emission Tomography Radiotracer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Ametamey SM, Kessler LJ, Honer M (2006) Radiosynthesis and preclinical evaluation of [11C]-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5 (mGluR5) J Nuc Med 47:698–705Google Scholar
  2. Delaforge M (1998) Importance of metabolism in pharmacological studies: possible in vitro predictability. Nucl Med Biol 25:705–709PubMedCrossRefGoogle Scholar
  3. Honer M, Hengerer B, Blagoev M et al. (2006) Comparison of 18F-FDOPA, 18F-FMT and 18F-FECNT for imaging dopaminergic neurotransmission in mice. Nucl Med Biol (in press)Google Scholar
  4. Hume SP, Gunn RN, Jones T (1998) Pharmacological constraints associated with positron emission tomographic scanning of small laboratory animals. Eur J Nucl Med 25:173–176PubMedCrossRefGoogle Scholar
  5. Hume SP, Lammertsma AA, Myers R et al. (1996) The potential of high resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease. J Neurosci Methods 15:103–112Google Scholar
  6. Jagoda EM, Vaquero JJ, Seidel J et al. (2004) Experiment assessment of mass effects in the rat:implications for small animal PET imaging. Nucl Med Biol 31:771–779PubMedCrossRefGoogle Scholar
  7. Kung MP, Kung HF (2005) Mass effect of injected dose in small rodent imaging by SPECT and PET. Nucl Med Biol 32:673–678PubMedCrossRefGoogle Scholar
  8. Ma Y, Kiesewetter D, Lang L et al. (2003) Application of LC-MS to the analysis of new radiopharmaceuticals. Mol Imaging Biol 5:397–403PubMedCrossRefGoogle Scholar
  9. Matsumura A, Mizokawa S, Tanaka M et al. (2003) Assessment of microPET performance in analyzing the rat brain under different types of anesthesia: comparison between quantitative data obtained with microPET and ex vivo autoradiography. NeuroImage 20:2040–2050PubMedCrossRefGoogle Scholar
  10. Momosaki S, Hatano K, Kawasumi Y et al. (2004) Rat-PET study without anesthesia: anesthetics modify the dopamine D1 receptor binding in rat brain. Synapse 54:207–213PubMedCrossRefGoogle Scholar
  11. Opacka Juffry J, Ahier RG, Cremer JE (1991) Nomifensine-induced increase in extracellular striatal dopamine is enhanced by isoflurane anaesthesia. Synapse 7:169–171PubMedCrossRefGoogle Scholar
  12. Osman S, Lundkvist C, Pike VW et al. (1996) Characterization of the radioactive metabolites of the 5-HT1A receptor radioligand [O-methyl-11C]-WAY100635 in human and primate plasma by HPLC: Comparison of the behaviour of an identified radioactive metabolite with parent radioligand in monkey using PET. Nucl Med Biol 23:627–634PubMedCrossRefGoogle Scholar
  13. Pike VW, McCarron JA, Hume SP et al. (1995) Preclinical development of a radioligand for studies of central 5-HT1A receptors in vivo-[11C]-WAY100635. Med Chem Res 5:208–227Google Scholar
  14. Shiue CY, Shiue GG, Cornish KG et al. (1995) PET study of the distribution of 11C-fluoxetine in a monkey brain. Nucl Med Biol 22:613–616PubMedCrossRefGoogle Scholar
  15. Tsukada H, Nishiyama S, Kakiuchi T et al. (1999) Isoflurane anesthesia enhances the inhibitory effects of cocaine and GBR12909 on dopamine transporter: PET studies in combination with microdialysis in the monkey brain. Brain Res 849:85–96PubMedCrossRefGoogle Scholar
  16. Votaw J, Byas-Smith M, Hua J et al. (2003) Interaction of isoflurane with the dopamine transporter. Anesthesiology 98:404–411PubMedCrossRefGoogle Scholar
  17. Wyss MT, Honer M, Schubiger PA et al. (2005) NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours. Eur J Nucl Med Mol Imaging 33:311–318PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • S. M. Ametamey
    • 1
  • M. Honer
    • 2
  1. 1.Animal Imaging Center-PET, Center for Radiopharmaceutical Science of ETH, PSI and USZETH-Hönggerberg, D-CHABZürichSwitzerland
  2. 2.Center for Radiopharmaceutical Science of ETH, PSI and USZ, Department of Chemistry and Applied BiosciencesETH-Hönggerberg D-CHABZürichSwitzerland

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