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Non-invasive methods to study drug disposition: Positron Emission Tomography Detection and quantification of brain receptors in man

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Summary

Positron emission tomography (PET) has been used mostly for the study of brain blood flow and metabolism in normal controls and in a variety of neurological and psychiatric conditions. With the appropriate radiotracers, PET also allows non-invasive imaging and quantification of a growing list of neuroreceptors, the target of most psychotropic drugs. For example,11C-carfentanil and11C-diprenorphine, two potent opiate ligands, have been used to label opiate receptors in vivo in man. Methods have been developed to quantify receptor studies with PET in terms of receptor density and affinity. PET is a unique tool that now allows measurement of receptor occupancy in vivo and could be used by the pharmacologist to optimize drug treatment.

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References

  1. Phelps M.E., Mazziotta J.C. (1985): Positron emission tomography: human brain function and biochemistry. Science, 228, 799–809.

    Article  CAS  PubMed  Google Scholar 

  2. Mazziotta J.C., Phelps M.E., Plummer D., Kuhl D.E. (1981): Quantitation in positron emission tomography: 5. physical-anatomical effects. J. Comp. Assist Tomogr., 5, 134–743.

    Google Scholar 

  3. Frost J.J. (1986): Imaging neuronal biochemistry by emission computed tomography: focus on neuroreceptors. Trends Pharmacol. Sei., 7, 490–496.

    Article  CAS  Google Scholar 

  4. Sadzot B., Frost J.J., Wagner H.N., Jr. (1989): In vivo labeling of central benzodiazepine receptors with the partial inverse agonist [3H]-Ro 15-4513. Brain Res., 491, 128–135.

    Article  CAS  PubMed  Google Scholar 

  5. Hartvig P., Bergström K., Lindberg B., et al. (1984): Kinetics of11C-labeled opiates in the brain of rhesus monkeys. J. Pharmacol. Exp. Therap., 230, 250–255.

    CAS  Google Scholar 

  6. Mather L.E. (1983): Clinical pharmacokinetics of fentanyl and its newer derivatives. Clin. Pharmacokin, 8, 422–446.

    Article  CAS  Google Scholar 

  7. Dannais R.F., Ravert H.T., Frost J.J., Wilson A.A., Burns H.D., Wagner H.N., Jr. (1985): Radiosynthesis of an opiate receptor binding radiotracer: [11C]carfentanil. Int J. Appl. Radiat Isot, 36, 303–306.

    Article  Google Scholar 

  8. Frost J.J., Wagner H.N., Jr., Dannais R.F., et al. (1985): Imaging opiate receptors in the human brain by positron emission tomography. J. Comput Ass. Tomogr, 9, 231–236.

    Article  CAS  Google Scholar 

  9. Lever J.R., Dannals R.F., Wilson A.A., Ravert H.T., Wagner H.N., Jr. (1987): Synthesis of carbon-11 labeled diprenorphine: a radioligand for positron emission tomographic studies of opiate receptors. Tet. Lett, 28, 4015–4018.

    Article  CAS  Google Scholar 

  10. Chang K-J., Hazum E., Cuatrecasas P. (1981): Novel opiate binding sites selective for benzomorphan drugs. Proc. Natl. Acad. Sei. USA, 78, 4141–4145.

    Article  CAS  Google Scholar 

  11. Kuhar M.J., Pert C.B., Snyder S.H. (1973): Regional distribution of opiate receptor binding in monkey and human brain. Nature, 245, 447–451.

    Article  CAS  PubMed  Google Scholar 

  12. Pfeiffer A., Pasi A., Mehraein P., Herz A. (1982): Opiate receptor binding sites in human brain. Brain Res, 248, 87–96.

    Article  CAS  PubMed  Google Scholar 

  13. Frost J J, Mayberg H.S, Sadzot B, et al. (1989): Comparison of11C-diprenorphine and11C-carfentanil binding to opiate receptors in man by positron emission tomography. J. Cereb. Blood Flow Metab, In press.

  14. Huang S.C., Barrio J.R., Phelps M.E. (1986): Neuroreceptor assay with positron emission tomography: equilibrium versus dynamic approaches. J. Cereb. Blood Flow Metab, 6, 515–521.

    CAS  PubMed  Google Scholar 

  15. Mintun M.A., Raichle M.E., Kilboum M.R., Wooten G.F., Welch M.J. (1984): A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann. Neurol, 15, 217–227.

    Article  CAS  PubMed  Google Scholar 

  16. Huang S-C., Bahn M.M., Barrio J.R., et al. (1989): A double injection technique for the in vivo measurement of dopamine D2-receptor density in monkeys with 3-(2′-[18F]fluoroethyl)spiperone and dynamic positron emission tomography. J. Cereb. Blood Flow Metab, 9, 850–858.

    CAS  PubMed  Google Scholar 

  17. Farde L., Eriksson L., Blomquist G., Halldin C. (1989): Kinetic analysis of central [11C]raclopride binding to D2-dopamine receptors studied by PET — A comparison to the equilibrium analysis. J. Cereb. Blood Flow Metab, 9, 696–708.

    CAS  PubMed  Google Scholar 

  18. Frost J.J., Sadzot B., Mayberg H.S., et al. (1989): Estimation of receptor number and affinity for11C-diprenorphine binding to opiate receptors in man by PET. J. Cereb. Blood Flow Metab, 9 (Suppll), S192.

    Google Scholar 

  19. Frost J.J., Mayberg H.S., Fisher R.S., et al. (1988) Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy. Ann. Neurol., 23, 231–237.

    Article  CAS  PubMed  Google Scholar 

  20. Savic I, Persson A, Roland P, Pauli S., Sedvall G, Widen L. (1988): In vivo demonstration of reduced benzodiazepine binding inhuman epileptic foci. Lancet, Oct 15, 863–866.

  21. Wong D.F., Wagner H.N., Tune L.E., et al. (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science, 234, 1558–1563.

    Article  CAS  PubMed  Google Scholar 

  22. Lee M.C., Wagner H.N., Jr., Tanada S., Frost J.J., Bice A.N., Dannais R.F. (1988): Duration of occupancy of opiate receptors by naltrexone. J. Nucl. Med., 29, 1207–1211.

    CAS  PubMed  Google Scholar 

  23. Smith M., Wolf A.P., Brodie J.D., et al. (1988): Serial [18F]N-methylspiperidol PET studies to measure changes in antipsychotic drug D2 receptor occupancy in schizophrenic patients. Biol Psychiatr., 23, 653–663.

    Article  CAS  Google Scholar 

  24. Wong D.F., Wagner H.N., Jr, Dannais R.F., et al. (1984): Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science, 226, 1393–1396.

    Article  CAS  PubMed  Google Scholar 

  25. Bice A.N., Wagner H.N., Jr., Frost J.J., et al. (1986): Simplified detection system for neuroreceptor studies in the human brain J. Nucl. Med., 27, 184–191.

    CAS  Google Scholar 

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Sadzot, B., Franck, G. Non-invasive methods to study drug disposition: Positron Emission Tomography Detection and quantification of brain receptors in man. Eur. J. Drug Metab. Pharmacokinet. 15, 135–142 (1990). https://doi.org/10.1007/BF03190196

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