RT Journal Article
SR Electronic
T1 Dopamine D1 Receptor Agonist PET Tracer Development: Assessment in Non-Human Primates
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.120.256008
DO 10.2967/jnumed.120.256008
A1 Olivier Barret
A1 Lei Zhang
A1 David Alagille
A1 Cristian C. Constantinescu
A1 Christine Sandiego
A1 Caroline Papin
A1 Jenna M. Sullivan
A1 Thomas Morley
A1 Vincent M. Carroll
A1 John Seibyl
A1 Jianqing Chen
A1 Chewah Lee
A1 Anabella Villalobos
A1 David Gray
A1 Timothy J. McCarthy
A1 Gilles Tamagnan
YR 2021
UL http://jnm.snmjournals.org/content/early/2021/02/12/jnumed.120.256008.abstract
AB Objective: Non-catechol based high affinity selective dopamine D1 receptor (D1R) agonists were recently described, and candidate PET ligands were selected based on favorable properties. The objective of this study was to characterize in vivo in non-human primates two novel D1R agonist PET radiotracers, racemic 18F-MNI-800 and its more active atropisomeric (-)-enantiomer 18F-MNI-968. Methods: Ten brain PET experiments were conducted with 18F-MNI-800 in two adult rhesus macaques and two adult cynomolgus macaques, and eight brain PET experiments were conducted with 18F-MNI-968 in two adult rhesus macaques and two adult cynomolgus macaques. PET data were analyzed with both plasma-input and reference-region based methods. Whole-body PET images were acquired with 18F-MNI-800 for radiation dosimetry estimates in two adult rhesus macaques. Results: 18F-MNI-800 and 18F-MNI-968 exhibited regional uptake consistent with D1 receptor distribution. Specificity and selectivity were demonstrated by dose-dependent blocking with the D1 antagonist SCH-23390. 18F-MNI-968 showed a 30% higher specific signal compared to 18F-MNI-800, with a binding potential BPND of ~0.3 in the cortex and ~1.1 in the striatum. Dosimetry radiation exposure was favorable, with an effective dose of ~0.023 mSv/MBq. Conclusion: 18F-MNI-968 (18F-PF-0110) has significant potential as a D1R agonist PET radiotracer, and further characterization in human subjects is warranted.