Purpose: The aim of this study was to evaluate the suitability of [ <sup>11</sup>C]SCH442416 for the in vivo imaging of adenosine A<sub>2A</sub> receptors. Methods: In rats and Macaca nemestrina, we evaluated the time course of the cerebral distribution of [<sup>11</sup>C]SCH442416. Furthermore, in rats we investigated the rate of metabolic degradation, the inhibitory effects of different drugs acting on adenosine or dopamine receptors and the modification induced by the intrastriatal administration of quinolinic acid (QA). Results: The rate of metabolic degradation of [<sup>11</sup>C]SCH442416 in rats was slow; 60 min after tracer injection, more than 40% of total plasma activity was due to unmetabolised [<sup>11</sup>C]SCH442416. At the time of maximum uptake, radioactive metabolites represented only 6% of total extractable activity in the cerebellum and less than 1% in the striatum. In the striatum, the region with the highest expression of A<sub>2A</sub> receptors, the in vivo uptake of [ <sup>11</sup>C]SCH442416 was significantly reduced only by drugs acting on A<sub>2A</sub> receptors or by QA, a neurotoxin that selectively reduces the number of intrastriatal GABAergic neurons. Position emission tomography (PET) studies in monkeys indicated that the tracer rapidly accumulates in brain, reaching maximum uptake between 5 and 10 min. Twenty minutes after the injection, radioactivity concentration in the striatum was two times that in the cerebellum. Conclusion: The specificity of binding, the rank order of regional distribution in the brain of rats and M. nemestrina, the good signal to noise ratios and the low amount of radioactive metabolites in brain and periphery indicate that [<sup>11</sup>C]SCH442416 is a promising tracer for the in vivo imaging of A<sub>2A</sub> adenosine receptors using PET. © Springer-Verlag 2004.

Moresco, R., Todde, S., Belloli, S., Simonelli, P., Panzacchi, A., Rigamonti, M., et al. (2005). In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 32(4), 405-413 [10.1007/s00259-004-1688-5].

In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416

MORESCO, ROSA MARIA;TODDE, SERGIO CAMILLO;SIMONELLI, PASQUALE;KIENLE, MARZIA DONATELLA;FAZIO, FERRUCCIO
2005

Abstract

Purpose: The aim of this study was to evaluate the suitability of [ 11C]SCH442416 for the in vivo imaging of adenosine A2A receptors. Methods: In rats and Macaca nemestrina, we evaluated the time course of the cerebral distribution of [11C]SCH442416. Furthermore, in rats we investigated the rate of metabolic degradation, the inhibitory effects of different drugs acting on adenosine or dopamine receptors and the modification induced by the intrastriatal administration of quinolinic acid (QA). Results: The rate of metabolic degradation of [11C]SCH442416 in rats was slow; 60 min after tracer injection, more than 40% of total plasma activity was due to unmetabolised [11C]SCH442416. At the time of maximum uptake, radioactive metabolites represented only 6% of total extractable activity in the cerebellum and less than 1% in the striatum. In the striatum, the region with the highest expression of A2A receptors, the in vivo uptake of [ 11C]SCH442416 was significantly reduced only by drugs acting on A2A receptors or by QA, a neurotoxin that selectively reduces the number of intrastriatal GABAergic neurons. Position emission tomography (PET) studies in monkeys indicated that the tracer rapidly accumulates in brain, reaching maximum uptake between 5 and 10 min. Twenty minutes after the injection, radioactivity concentration in the striatum was two times that in the cerebellum. Conclusion: The specificity of binding, the rank order of regional distribution in the brain of rats and M. nemestrina, the good signal to noise ratios and the low amount of radioactive metabolites in brain and periphery indicate that [11C]SCH442416 is a promising tracer for the in vivo imaging of A2A adenosine receptors using PET. © Springer-Verlag 2004.
Articolo in rivista - Articolo scientifico
[11C]SCH442416,PET, recettori adenosina
English
2005
32
4
405
413
none
Moresco, R., Todde, S., Belloli, S., Simonelli, P., Panzacchi, A., Rigamonti, M., et al. (2005). In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 32(4), 405-413 [10.1007/s00259-004-1688-5].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/1346
Citazioni
  • Scopus 62
  • ???jsp.display-item.citation.isi??? 54
Social impact