title: Kinetic modeling, test-retest, and dosimetry of 123I-MNI-420 in humans.
abstract: 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 (123)I-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 (123)I-MNI-420 brain SPECT studies, and 2 participated in whole-body planar imaging evaluating (123)I-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
  (123)I-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.
  
  
  CONCLUSIONS
  The data indicate that (123)I-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 (123)I-MNI-420 offers the possibility of investigating A2A activity in specific conditions and evaluating drug occupancy for A2A candidate therapeutics.
authors: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors: Adriana Alexandre S
authors: AA
authors: Tavares
authors: Jeffery C
authors: JC
authors: Batis
authors: Caroline
authors: C
authors: Papin
authors: Danna
authors: D
authors: Jennings
authors: David
authors: D
authors: Alagille
authors: David S
authors: DS
authors: Russell
authors: Christine
authors: C
authors: Vala
authors: Hsiaoju
authors: H
authors: Lee
authors: Ronald M
authors: RM
authors: Baldwin
authors: I George
authors: IG
authors: Zubal
authors: Kenneth L
authors: KL
authors: Marek
authors: John P
authors: JP
authors: Seibyl
authors: Olivier
authors: O
authors: Barret
authors: Gilles D
authors: GD
authors: Tamagnan
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011874:Radiometry; D015203:Reproducibility of Results; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: C583370:7-(2-(4-(2-fluoro-4-iodophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidin-5-amine; D006575:Heterocyclic Compounds, 3-Ring
keywords: 123I-MNI-420; A2A receptors; SPECT; dosimetry; test–retest