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.