Quantification of A1R with [11C]MPDX PET


Adenosine receptor subtype A1R can be quantified with PET and radiolabelled xanthine antagonists, such as [11C]MPDX, 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine, in human and rat brain (Kimura et al., 2004; Paul et al., 2011).


A1R density in the brain decreases by age (Mishina et al., 2012).

Receptor occupancy

[11C]MPDX can be used to study occupancy by A1R antagonists (for example caffeine) but not agonists (Paul et al., 2014). Plasma clearance of the tracer is strongly affected by antagonists and agonists (Paul et al., 2014), therefore SUV or population average input function methods cannot be recommended.

Metabolites in plasma

In rats the metabolism of [11C]MPDX is slow, the fraction of parent compound being 82-84% at 60 min (Paul et al., 2011).

Reference region

Cerebellar cortex contains very low density of A1 receptors (Fastbom et al., 1987), and has therefore been used as reference region in clinical protocols (Kimura et al., 2004; Fukumitsu et al., 2008). In certain cortical regions the A1R density may be even lower than in cerebellar cortex, leading to negative BPND (Fukumitsu et al., 2008).

P-glycoprotein at the blood-brain barrier (BBB) limits the uptake of [11C]MPDX. The effect is usually the same in the region of interest and in the reference region, thus the BPND estimates are not affected (Ishiwata et al., 2007). However, some diseases may affect the integrity of BBB differently in different brain areas.

Suggested analysis method for TPC


Logan plot with arterial metabolite corrected plasma input function is recommended, with linear fitting from 10 min to at least 35-40 min after injection (Kimura et al., 2004). In clinical PET protocol the BPND can be calculated as DVR-1, using cerebellum as reference region (Fukumitsu et al., 2008).

Occupancy can be measured using modified Lassen plot (Paul et al., 2011 and 2014).

See also:


Fastbom J, Pazos A, Probst A, Palacios JM. Adenosine A1 receptors in the human brain: a quantitative autoradiographic study. Neuroscience 1987; 22: 827-839.

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): 511-515.

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): 32-37.

Fukumitsu N, Ishii K, Kimura Y, Oda K, Hashimoto M, Suzuki M, Ishiwata K. Adenosine A1 receptors using 8-dicyclopropylmethyl-1-[11C]methyl-3-propylxanthine PET in Alzheimer's disease. Ann Nucl Med. 2008; 22: 841-847.

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): 377-382.

Ishiwata K, Kawamura K, Yanai K, Hendrikse NH. In vivo evaluation of P-glycoprotein modulation of 8 PET radioligands used clinically. J Nucl Med. 2007; 48(1): 81-87.

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): 975-981. doi: 10.1016/j.nucmedbio.2004.06.005.

Mishina M, Ishiwata K. Adenosine receptor PET imaging in human brain. Int Rev Neurobiol. 2014; 119: 51-69.

Mishina M, Kimura Y, Naganawa M, Ishii K, Oda K, Sakata M, Toyohara J, Kobayashi S, Katayama Y, Ishiwata K. Differential effects of age on human striatal adenosine A1 and A2A receptors. Synapse 2012; 66(9): 832-839.

Paul S, Khanapur S, Rybczynska AA, Kwizera C, Sijbesma JWA, Ishiwata K, Willemsen ATM, Elsinga PH, Dierckx RAJO, van Waarde A. Small-animal PET study of adenosine A1 receptors in rat brain: blocking receptors and raising extracellular adenosine. J Nucl Med. 2011; 52: 1293-1300.

Paul S, Khanapur S, Sijbesma JW, Ishiwata K, Elsinga PH, Meerlo P, Dierckx RA, van Waarde A. Use of 11C-MPDX and PET to study adenosine A1 receptor occupancy by nonradioactive agonists and antagonists. J Nucl Med. 2014; 55: 315-320.

Shimada Y, Ishiwata K, Kiyosawa M, Nariai T, Oda K, Toyama H, Suzuki F, Ono K, Senda M. Mapping adenosine A1 receptors in the cat brain by positron emission tomography with [11C]MPDX. Nucl Med Biol. 2002; 29: 29-37.


Updated at: 2015-08-13
Created at: 2009-03-26
Written by: Vesa Oikonen