Quantitation of the A 2A Adenosine Receptor Density in the Striatum of Mice and Pigs with [ 18 F]FLUDA by Positron Emission Tomography.

The cerebral expression of the A _2A adenosine receptor (A _2A AR) is altered in neurodegenerative diseases such as Parkinson's (PD) and Huntington's (HD) diseases, making these receptors an attractive diagnostic and therapeutic target. We aimed to further investigate the pharmacokinetic properties in the brain of our recently developed A _2A AR-specific antagonist radiotracer [ ¹⁸ F]FLUDA. For this purpose, we retrospectively analysed dynamic PET studies of healthy mice and rotenone-treated mice, and conducted dynamic PET studies with healthy pigs. We performed analysis of mouse brain time-activity curves to calculate the mean residence time (MRT) by non-compartmental analysis, and the binding potential ( BP _ND ) of [ ¹⁸ F]FLUDA using the simplified reference tissue model (SRTM). For the pig studies, we performed a Logan graphical analysis to calculate the radiotracer distribution volume ( V _T ) at baseline and under blocking conditions with tozadenant. The MRT of [ ¹⁸ F]FLUDA in the striatum of mice was decreased by 30% after treatment with the A _2A AR antagonist istradefylline. Mouse results showed the highest BP _ND (3.9 to 5.9) in the striatum. SRTM analysis showed a 20% lower A _2A AR availability in the rotenone-treated mice compared to the control-aged group. Tozadenant treatment significantly decreased the V _T (14.6 vs. 8.5 mL · g ^-1 ) and BP _ND values (1.3 vs. 0.3) in pig striatum. This study confirms the target specificity and a high BP _ND of [ ¹⁸ F]FLUDA in the striatum. We conclude that [ ¹⁸ F]FLUDA is a suitable tool for the non-invasive quantitation of altered A _2A AR expression in neurodegenerative diseases such as PD and HD, by PET.