RT Journal Article SR Electronic T1 Kinetic Modeling, Test–Retest, and Dosimetry of 123I-MNI-420 in Humans JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1760 OP 1767 DO 10.2967/jnumed.113.119933 VO 54 IS 10 A1 Adriana Alexandre S. Tavares A1 Jeffery C. Batis A1 Caroline Papin A1 Danna Jennings A1 David Alagille A1 David S. Russell A1 Christine Vala A1 Hsiaoju Lee A1 Ronald M. Baldwin A1 I. George Zubal A1 Kenneth L. Marek A1 John P. Seibyl A1 Olivier Barret A1 Gilles D. Tamagnan YR 2013 UL http://jnm.snmjournals.org/content/54/10/1760.abstract AB In vivo imaging of adenosine 2A receptors (A2A) in the brain has attracted significant interest from the scientific community, because studies have shown that dysregulation of these receptors is implicated in a variety of neurodegenerative and psychiatric disorders, including Parkinson and Huntington diseases. This work aimed to describe the kinetic properties, test–retest results, and dosimetry estimates of 123I-MNI-420, a SPECT radiotracer for the in vivo imaging of A2A in the brain. Methods: Nine healthy human subjects were enrolled in this study; 7 completed 123I-MNI-420 brain SPECT studies, and 2 participated in whole-body planar imaging evaluating 123I-MNI-420 biodistribution and dosimetry. For 3 of the brain SPECT studies, arterial blood was collected for invasive modeling. Noninvasive models were also explored, including Logan graphical analysis and simplified reference tissue models. Test–retest reliability was assessed in 4 subjects. To evaluate radiotracer biodistribution and dosimetry, serial whole-body images were acquired immediately after injection and at selected time points after injection. Urine samples were collected over a period of 21 h to calculate urinary excretion. Results: 123I-MNI-420 rapidly entered the human brain and displayed uptake consistent with known A2A densities. At pseudoequilibrium (reached at 90 min after radiotracer injection), stable target-to-cerebellum ratios of around 1.4–2.0 were determined. Binding potentials around 0.8–1.2 were estimated using different kinetic models and the cerebellum as the reference region. Average test–retest variability in the striatum was 4.8%, 3.5%, and 6.5% for the simplified reference tissue model, Logan graphical analysis, and standardized uptake value ratio methods, respectively. The estimated radiation effective dose determined from whole-body studies was 0.036 mSv/MBq. Conclusion: The data indicate that 123I-MNI-420 is a useful SPECT radiotracer for imaging A2A in the brain and has radiation doses that would allow for multiple scans in the same research subject each year. The availability of 123I-MNI-420 offers the possibility of investigating A2A activity in specific conditions and evaluating drug occupancy for A2A candidate therapeutics.