Kinetic Modeling, Test-Retest, and Dosimetry of I-123-MNI-420 in Humans

Adriana Alexandre S. Tavares*, Jeffery C. Batis, Caroline Papin, Danna Jennings, David Alagille, David S. Russell, Christine Vala, Hsiaoju Lee, Ronald M. Baldwin, I. George Zubal, Kenneth L. Marek, John P. Seibyl, Olivier Barret, Gilles D. Tamagnan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In vivo imaging of adenosine 2A receptors (A(2A)) 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 I-123-MNI-420, a SPECT radiotracer for the in vivo imaging of A(2A) in the brain. Methods: Nine healthy human subjects were enrolled in this study; 7 completed I-123-MNI-420 brain SPECT studies, and 2 participated in whole-body planar imaging evaluating I-123-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: I-123-MNI-420 rapidly entered the human brain and displayed uptake consistent with known A(2A) 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 I-123-MNI-420 is a useful SPECT radiotracer for imaging A(2A) in the brain and has radiation doses that would allow for multiple scans in the same research subject each year. The availability of I-123-MNI-420 offers the possibility of investigating A(2A) activity in specific conditions and evaluating drug occupancy for A(2A) candidate therapeutics.

Original languageEnglish
Pages (from-to)1760-1767
Number of pages8
JournalJournal of Nuclear Medicine
Volume54
Issue number10
DOIs
Publication statusPublished - 1 Oct 2013

Keywords

  • A(2A) receptors
  • SPECT
  • I-123-MNI-420
  • test-retest
  • dosimetry
  • ADENOSINE A(2A) RECEPTOR
  • HEALTHY-HUMAN SUBJECTS
  • PARKINSONS-DISEASE
  • HUMAN BRAIN
  • DOPAMINE TRANSPORTERS
  • COMPUTED-TOMOGRAPHY
  • RADIATION-DOSIMETRY
  • GRAPHICAL ANALYSIS
  • PET DATA

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