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).
[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).
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).
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Tags: Adenosine receptor
Created at: 2009-03-26
Updated at: 2015-08-13
Written by: Vesa Oikonen