Characterization in humans of ¹⁸F-MNI-444, a PET radiotracer for brain adenosine 2A receptors

PET with selective adenosine 2A receptor (A_2A) radiotracers can be used to study a variety of neurodegenerative and neuropsychiatric disorders in vivo and to support drug-discovery studies targeting A_2A. The aim of this study was to describe the first in vivo evaluation of ¹⁸F-MNI-444, a novel PET radiotracer for imaging A_2A, in healthy human subjects. Methods: Ten healthy human volunteers were enrolled in this study; 6 completed the brain PET studies and 4 participated in the whole-body PET studies. Arterial blood was collected for invasive kinetic modeling of the brain PET data. Noninvasive methods of data quantification were also explored. Test-retest reproducibility was evaluated in 5 subjects. Radiotracer distribution and dosimetry was determined using serial whole-body PET images acquired over 6 h post-radiotracer injection. Urine samples were collected to calculate urinary excretion. Results: After intravenous bolus injection, ¹⁸F-MNI-444 rapidly entered the brain and displayed a distribution consistent with known A_2A densities in the brain. Binding potentials ranging from 2.6 to 4.9 were measured in A_2A-rich regions, with an average test-retest variability of less than 10%. The estimated whole-body radiation effective dose was approximately 0.023 mSv/MBq. Conclusion: ¹⁸F-MNI-444 is a useful PET radiotracer for imaging A_2A in the human brain. The superior in vivo brain kinetic properties of ¹⁸F-MNI-444, compared with previously developed A_2A radiotracers, provide the opportunity to foster global use of in vivo A_2A PET imaging in neuroscience research.