NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

Cover of Molecular Imaging and Contrast Agent Database (MICAD)

Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

Show details


, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD, vog.hin.mln.ibcn@dacim

Created: ; Last Update: July 6, 2008.

Chemical name:[1-methyl-11C]8-Dicyclopropylmethyl-1-methyl-3-propylxanthineimage 8149029 in the ncbi pubchem database
Abbreviated name:[11C]MPDX
Agent Category:Compound
Target:Adenosine A1 receptor
Target Category:Receptor binding
Method of detection:PET
Source of signal:11C
  • Checkbox In vitro
  • Checkbox Rodents
  • Checkbox Non-primate non-rodent mammals
  • Checkbox Non-human primates
  • Checkbox Humans
Click on the above structure for additional information in PubChem.



Adenosine is an endogenous nucleoside that modulates a number of physiologic functions in the central nervous system (CNS) and in peripheral organs, such as the heart, kidney, and muscle (1, 2). The effect is mediated by two major subtypes of receptors (A1 and A2A) and two minor subtypes (A2B and A3). In the CNS, A1 receptors are present both pre- and postsynaptically in the hippocampus, cerebral cortex, thalamus, striatum, and cerebellum. A2A receptors are highly concentrated and colocalized with dopamine D1 and D2 receptors in the striatum, nucleus accumbens, and olfactory tubercle. A2A receptors are also present in the hippocampus and cortex. A2B receptors are widely distributed, with high concentrations in the gastrointestinal tract. A3 receptors are also widely distributed, with high concentrations in the testis. A1 and A3 receptors mediate inhibition of adenylyl cyclase, whereas A2A and A2B receptors mediate stimulation. Changes in adenosine functions are implicated in epilepsy, ischemic cerebral stroke, movement disorders, sleep disorders, and psychiatric disorders (3-5).

A1 receptors have been studied in vivo by positron emission tomography (PET) using [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine ([11C]MPDX), a methyl xanthine analog of KF15372 with selective A1 antagonistic activity (6). [11C]MPDX is being developed as a PET agent for the non-invasive study of A1 receptors in the human brain.



In the report by Noguchi et al. (7), [11C]MPDX was synthesized by alkylation of the 1-N-desmethyl precursor (8-dicyclopropylmethyl-3-propylxanthine) with [11C]methyl iodide in the presence of NaH with subsequent purification by high-performance liquid chromatography (HPLC). Radiochemical purity was greater than 98%. The average specific activity was 49 GBq/μmol (1.3 Ci/μmol) at the end of synthesis. Total synthesis time was 45-60 min.

Kawamura et al. (8) described the synthesis of [11C]MPDX from the desmethyl precursor with [11C]methyl triflate in the presence of NaOH. This procedure provided an improved radiochemical yield of 34.3% based on [11C]methyl triflate. No time of synthesis or specific activity was reported.

In Vitro Studies: Testing in Cells and Tissues


The reported Ki values of MPDX and KF15372 for the A1 receptors were 4.2 nM and 3.0 nM, respectively (7). The Ki values for both antagonists for A2A receptors were >100 nM.

Animal Studies



Biodistribution studies in normal mice showed high accumulation of radioactivity in the liver (8.5% of injected dose (ID)/g), followed by the small intestine (3.8% ID/g), pancreas (3.2% ID/g), kidney (2.3% ID/g), and spleen (1.9% ID/g) at 30 min after injection of [11C]MPDX (7). The level of radioactivity was low in the brain (0.7% ID/g) and blood (1.5% ID/g). Coadministration of the A1 antagonist KF15372, but not A2A antagonist KF17837, decreased the accumulation in the brain in a dose-dependent manner at 15 min post injection. About 22-27% and 62-65% of radioactivity in the plasma and cerebral cortex, respectively, was intact [11C]MPDX at 30 min post injection.

Kiyosawa et al. (9) studied the changes in the distribution of central benzodiazepine and presynaptic A1 receptors in the superior colliculus (SC) and visual cortex (VC) of rats after monocular enucleation as measured by ex vivo autoradiography. The uptake of [14C]deoxyglucose in the SC was decreased by ~40% immediately after enucleation and gradually recovered. The binding of [11C]flumazenil to central benzodiazepine receptors in the contralateral SC was increased by 33% at week 2 and then returned to the pre-enucleation levels. The uptake of [11C]MPDX by the A1 receptors in the contralateral SC decreased by ~67% on day 5 after enucleation and remained depressed thereafter. In the contralateral VC, the uptake of [14C]deoxyglucose decreased by ~40% immediately after enucleation followed by a gradual recovery, whereas the accumulation of [11C]flumazenil and [11C]MPDX was not affected. Axon degeneration decreased the A1 receptor density and produced a transient increase of postsynaptic central benzodiazepine receptor density in the enucleated rats as measured by ex vivo autoradiography.

Other Non-Primate Mammals


Shimada et al. (6) obtained PET images of the brain in cats after injection of 199 MBq (5.4 mCi) of [11C]MPDX. The regional brain distribution and kinetics of [11C]MPDX were studied with magnetic resonance imaging co-registration. The cerebral cortex exhibited the highest accumulation of [11C]MPDX (distribution volume (DV) = 4.2 ± 1.7) followed by the striatum (DV = 3.8 ± 1.3), cerebellum (DV = 3.5 ± 1.2), thalamus (DV = 3.1 ± 1.2), midbrain (DV = 2.6 ± 0.9), and whole brain (DV = 2.4 ± 0.8). Co-injection with unlabeled MDPX inhibited binding of [11C]MPDX to the regional brain areas.

Nariai et al. (10, 11) studied the adenosine A1 receptor with PET using [11C]MPDX in a cat cerebral ischemic model (middle cerebral artery occlusion and reperfusion). Eighteen adult cats underwent PET measurement of cerebral blood flow (CBF) with 15O-labeled water, A1 receptor measurement with [11C]MPDX, central benzodiazepine receptor measurement with [11C]flumazenil, and glucose metabolism measurement with [18F]fluorodeoxyglucose (FDG) after 60 min of occlusion. [11C]MPDX binding and [11C]flumazenil binding, but not CBF and FDG uptake, were significantly reduced in the groups with more severe ischemic insult than in the groups with no or milder insults. Of the two receptor ligands, the reduction rate of [11C]MPDX binding to A1 receptors was larger in the group that suffered fatal ischemic insult. Therefore, [11C]MPDX PET imaging was suitable for evaluating the function of adenosine A1 receptors in relation to cerebral ischemia.

Non-Human Primates


Using PET, Ishiwata et al. (12) obtained serial brain scans in 2 monkeys after injection of 91-141 MBq (2.5-3.8 mCi) of [11C]MPDX. Accumulation of radioactivity in the brain peaked at 5 min and then decreased for the final 60 min of study. The fraction of unchanged [11C]MPDX in blood samples, as determined by HPLC, was 78%, 70%, 54%, and 41% at 5, 15, 30, and 60 min, respectively.

Human Studies


Kimura et al. (13) reported on PET studies in 7 healthy volunteers after injection of 259-777 MBq (7-21 mCi) of [11C]MPDX. In Logan plot analysis, the striatum (0.55) exhibited the highest binding potential ((BP), cerebellum as a reference) for [11C]MPDX, followed by the thalamus (0.50), occipital cortex (0.40), parietal cortex (0.33), and temporal cortex (0.28). Fukumitsu et al. (14, 15) extended the human PET studies, using Logan plot analysis with arterial input. The DV was large in the striatum and thalamus, moderate in the cerebral cortices, and small in the cerebellum. The distribution pattern of [11C]MPDX in the brain was discretely different from that of CBF as measured by 15O-labeled water. At 60 min after injection of [11C]MPDX, 75% of plasma radioactivity was from the intact tracer. This percentage was much higher than those in rats (22-27%), cats (6.5%), and monkeys (41%). Naganawa et al. (16) reported that the DV and BP for [11C]MPDX in various brain regions could be accurately estimated without arterial blood sampling in 25 subjects. Internal dosimetry data for [11C]MPDX in humans are not available in the literature.


Fredholm B.B., Abbracchio M.P., Burnstock G., Daly J.W., Harden T.K., Jacobson K.A., Leff P., Williams M. Nomenclature and classification of purinoceptors. Pharmacol Rev. 1994;46(2):143–56. [PMC free article: PMC4976594] [PubMed: 7938164]
Palmer T.M., Stiles G.L. Adenosine receptors. Neuropharmacology. 1995;34(7):683–94. [PubMed: 8532135]
Dunwiddie T.V., Masino S.A. The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci. 2001;24:31–55. [PubMed: 11283304]
El Yacoubi M., Costentin J., Vaugeois J.M. Adenosine A2A receptors and depression Neurology 200361Suppl 611S82–7. [PubMed: 14663017]
von Lubitz D.K. Adenosine in the treatment of stroke: yes, maybe, or absolutely not? Expert Opin Investig Drugs. 2001;10(4):619–32. [PubMed: 11281813]
Shimada J., Suzuki F., Nonaka H., Karasawa A., Mizumoto H., Ohno T., Kubo K., Ishii A. 8-(Dicyclopropylmethyl)-1,3-dipropylxanthine: a potent and selective adenosine A1 antagonist with renal protective and diuretic activities. J Med Chem. 1991;34(1):466–9. [PubMed: 1992150]
Noguchi J., Ishiwata K., Furuta R., Simada J., Kiyosawa M., Ishii S., Endo K., Suzuki F., Senda M. Evaluation of carbon-11 labeled KF15372 and its ethyl and methyl derivatives as a potential CNS adenosine A1 receptor ligand. Nucl Med Biol. 1997;24(1):53–9. [PubMed: 9080475]
Kawamura K., Ishiwata K. Improved synthesis of [11C]SA4503, [11C]MPDX and [11C]TMSX by use of [11C]methyl triflate. Ann Nucl Med. 2004;18(2):165–8. [PubMed: 15195766]
Kiyosawa M., Ishiwata K., Noguchi J., Endo K., Wang W.F., Suzuki F., Senda M. Neuroreceptor bindings and synaptic activity in visual system of monocularly enucleated rat. Jpn J Ophthalmol. 2001;45(3):264–9. [PubMed: 11369376]
Nariai T., Shimada Y., Ishiwata K., Nagaoka T., Shimada J., Kuroiwa T., Ono K., Ohno K., Hirakawa K., Senda M. PET imaging of adenosine A(1) receptors with (11)C-MPDX as an indicator of severe cerebral ischemic insult. J Nucl Med. 2003;44(11):1839–44. [PubMed: 14602868]
Nariai T., Shimada Y., Ishiwata K., Nagaoka T., Shimada J., Kuroiwa T., Ono K.I., Hirakawa K., Senda M., Ohno K. PET neuroreceptor imaging as predictor of severe cerebral ischemic insult. Acta Neurochir Suppl. 2003;86:45–8. [PubMed: 14753402]
Ishiwata K., Nariai T., Kimura Y., Oda K., Kawamura K., Ishii K., Senda M., Wakabayashi S., Shimada J. Preclinical studies on [11C]MPDX for mapping adenosine A1 receptors by positron emission tomography. Ann Nucl Med. 2002;16(6):377–82. [PubMed: 12416575]
Kimura Y., Ishii K., Fukumitsu N., Oda K., Sasaki T., Kawamura K., Ishiwata K. Quantitative analysis of adenosine A1 receptors in human brain using positron emission tomography and [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine. Nucl Med Biol. 2004;31(8):975–81. [PubMed: 15607479]
Fukumitsu N., Ishii K., Kimura Y., Oda K., Sasaki T., Mori Y., Ishiwata K. Adenosine A1 receptor mapping of the human brain by PET with 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine. J Nucl Med. 2005;46(1):32–7. [PubMed: 15632030]
Fukumitsu N., Ishii K., Kimura Y., Oda K., Sasaki T., Mori Y., Ishiwata K. Imaging of adenosine A1 receptors in the human brain by positron emission tomography with [11C]MPDX. Ann Nucl Med. 2003;17(6):511–5. [PubMed: 14575390]
Naganawa M., Kimura Y., Nariai T., Ishii K., Oda K., Manabe Y., Chihara K., Ishiwata K. Omission of serial arterial blood sampling in neuroreceptor imaging with independent component analysis. Neuroimage. 2005;26(3):885–90. [PubMed: 15955498]


Search MICAD

Limit my Search:

Related information

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...