As shown in Figure 2, several 11 C PET radioligands of the A1R have been developed and tested thus far. The first PET radiotracer was developed by 11 C radiolabeling of the xanthene-derived A1R antagonist KF15372, [11 C]KF15372, and showed a specific and reversible brain uptake but an unacceptable high fraction of nonspecific binding that limited its use in preclinical evaluation of the A1R.83,84 [11 C]MPDX, another analog of A1R antagonist KF15372, was developed to measure regional A1R densities in the brain of rodent and in patients with diffuse axonal injury, a model for TBI.85 It detected an increase in A1R expression in areas surrounding the injuries in the brain, emphasizing on neuroprotective and neuromodulatory effects of A1R in TBI.85 Moreover, [11 C]MPDX was also used to investigate the cerebral density of A1Rs in early stages of PD and showed a higher binding potential in the temporal lobe of the patients with PD compared to the healthy controls.86 Similarly, [11 C]MPDX was used for mapping of the A1Rs in the brain of aged human compared to the young subjects and
