PT  - JOURNAL ARTICLE
AU  - Soumen Paul
AU  - Shivashankar Khanapur
AU  - Anna A. Rybczynska
AU  - Chantal Kwizera
AU  - Jurgen W.A. Sijbesma
AU  - Kiichi Ishiwata
AU  - Antoon T.M. Willemsen
AU  - Philip H. Elsinga
AU  - Rudi A.J.O. Dierckx
AU  - Aren van Waarde
TI  - Small-Animal PET Study of Adenosine A<sub>1</sub> Receptors in Rat Brain: Blocking Receptors and Raising Extracellular Adenosine
AID  - 10.2967/jnumed.111.088005
DP  - 2011 Aug 01
TA  - Journal of Nuclear Medicine
PG  - 1293--1300
VI  - 52
IP  - 8
4099  - http://jnm.snmjournals.org/content/52/8/1293.short
4100  - http://jnm.snmjournals.org/content/52/8/1293.full
SO  - J Nucl Med2011 Aug 01; 52
AB  - Activation of adenosine A1 receptors (A1R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A1R can be visualized using 8-dicyclopropylmethyl-1-11C-methyl-3-propyl-xanthine (11C-MPDX) and PET. This study aims to test whether 11C-MPDX can be used for quantitative studies of cerebral A1R in rodents. Methods: 11C-MPDX was injected (intravenously) into isoflurane-anesthetized male Wistar rats (300 g). A dynamic scan of the central nervous system was obtained, using a small-animal PET camera. A cannula in a femoral artery was used for blood sampling. Three groups of animals were studied: group 1, controls (saline-treated); group 2, animals pretreated with the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 mg, intraperitoneally); and group 3, animals pretreated (intraperitoneally) with a 20% solution of ethanol in saline (2 mL) plus the adenosine kinase inhibitor 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d] pyrimidine dihydrochloride (ABT-702) (1 mg). DPCPX is known to occupy cerebral A1R, whereas ethanol and ABT-702 increase extracellular adenosine. Results: In groups 1 and 3, the brain was clearly visualized. High uptake of 11C-MPDX was noted in striatum, hippocampus, and cerebellum. In group 2, tracer uptake was strongly suppressed and regional differences were abolished. The treatment of group 3 resulted in an unexpected 40%–45% increase of the cerebral uptake of radioactivity as indicated by increases of PET standardized uptake value, distribution volume from Logan plot, nondisplaceable binding potential from 2-tissue-compartment model fit, and standardized uptake value from a biodistribution study performed after the PET scan. The partition coefficient of the tracer (K1/k2 from the model fit) was not altered under the study conditions. Conclusion: 11C-MPDX shows a regional distribution in rat brain consistent with binding to A1R. Tracer binding is blocked by the selective A1R antagonist DPCPX. Pretreatment of animals with ethanol and adenosine kinase inhibitor increases 11C-MPDX uptake. This increase may reflect an increased availability of A1R after acute exposure to ethanol.