RT Journal Article
SR Electronic
T1 Dopamine D<sub>1</sub> Receptor Agonist PET Tracer Development: Assessment in Nonhuman Primates
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1307
OP 1313
DO 10.2967/jnumed.120.256008
VO 62
IS 9
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/62/9/1307.abstract
AB Non–catechol-based high-affinity selective dopamine D1 receptor (D1R) agonists were recently described, and candidate PET ligands were selected on the basis of favorable properties. The objective of this study was to characterize in vivo in nonhuman primates 2 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 on 2 adult rhesus macaques and 2 adult cynomolgus macaques, and 8 brain PET experiments were conducted with 18F-MNI-968 on 2 adult rhesus macaques and 2 adult cynomolgus macaques. PET data were analyzed with both plasma-input–based methods and reference-region–based methods. Whole-body PET images were acquired with 18F-MNI-800 from 2 adult rhesus macaques for radiation dosimetry estimates. Results: 18F-MNI-800 and 18F-MNI-968 exhibited regional uptake consistent with D1R 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 than 18F-MNI-800, with a nondisplaceable binding potential of approximately 0.3 in the cortex and approximately 1.1 in the striatum. Dosimetry radiation exposure was favorable, with an effective dose of about 0.023 mSv/MBq. Conclusion: 18F-MNI-968 has significant potential as a D1R agonist PET radiotracer, and further characterization in human subjects is warranted.