In Vivo PET Imaging of Adenosine 2A Receptors in Neuroinflammatory and Neurodegenerative Disease

Table 1

Currently available receptor binding radioligands.

	Affinity to (nM)/selectivity over other adenosine receptors	Characteristics of specific binding	with metabolite corrected arterial plasma input	receptor occupancy/blocking studies
TMSX	= 5.9/selectivity over A1: 270-fold [139]	BP in anterior and posterior putamen: 1.25 ± 0.17 and 1.20 ± 0.16, respectively (centrum semiovale as reference region) [19] DVR in striatum (clustered gray matter as reference region) 1.674 [141]	1.72 [134]; 1.66–1.69 [19]; 1.11 (striatum) [13]	Theophylline infusion reduced in putamen by 4.5% and in the nucleus caudatus by 8%. No effect on other areas [134].
Preladenant	= 1.1 = 2.5/selectivity over (human) A1, , A3: >1000-fold [143]	DVR in putamen 7.9 ± 2.3 (2 tissue model) 7.7 ± 1.9 (LGRM) (cerebellum as reference region) [129]	4.5 ± 1.3 [129]	Preladenant pretreatment reduced striatal to level of extrastriatal binding in rhesus monkeys [144].
MNI-444	= 2.8 [145]	BP 4.7 ± 0.63 (cerebellum as reference region) [130]	3.26 ± 0.98 (with LGA) [130]	Preblocking with Tozadenant or Preladenant reduced total binding (SUV) to the level of extrastriatal (cerebellum) binding at the highest dose in rhesus monkeys. Also <15% reduction in cerebellar with preblocking was observed [146].
SCH442416	= 0.048/selectivity over A1, , A3 >20000-fold [147]	BP 0.99 ± 0.21; (cerebellum as reference region) [15] 2.47 ± 0.84 (cerebellum as reference region) [148]	≈0.6 [149]	Preblocking with Preladenant led to dose-dependent receptor occupancy in the striatum (at 200 mg 88–105%), with corresponding decrease in SCH442416 binding (); [148].; Preblocking with vipadenant led to approximately 3-4-fold reduction SCH442416 in caudate and putamen and also to an up to 2-fold reduction in cerebellum. Dose-dependent receptor occupancy observed in putamen, caudate, nucleus accumbens, and cerebellum (on average from 74% to 95% with 2.5–100 mg dose), but not in thalamus [149].