In blood samples tracer quantification resulted in an activity level of 1.2 ± 0.6 %ID/g. Similar to [ 11 C]AZD1283, [ 18 F]12 displays only a low retention in blood, which is noteworthy given that P2Y12R is expressed on blood platelets. The highest signals of tracer uptake were measured in metabolic and excretory organs such as the liver with 19.6 ± 4.8 %ID/g and kidney 5.5 ± 1.1 %ID/g. As in vivo blocking experiments were not possible due to the unavailability of brain permeable P2Y12R inhibitors, microglia-depleted mice were used as negative controls. The feeding of the colony-stimulating factor-1 receptor (CSF1R) antagonist PLX-5622 to wild-type mice results in a near-total depletion of microglia with reduced P2Y12R expression after a three-week period of a chow diet. Dynamic PET imaging was carried out in microglia-depleted (PLX) mice (n = 8) and whole brain TACs were generated (Figure and). While the initial tracer uptake followed a similar kinetic profile to that observed in WT mice, the later plateau phase indicated reduced tracer retention in the CNS. This effect was most significant for the time period 25 -60 min p.i. (42% higher accumulation in WT, p = 0.0029, Figure ) and is further illustrated in the differential SUV scaled image comparing WT and PLX treated mice.