PT  - JOURNAL ARTICLE
AU  - Olivier Barret
AU  - Lei Zhang
AU  - David Alagille
AU  - Cristian C. Constantinescu
AU  - Christine Sandiego
AU  - Caroline Papin
AU  - Jenna M. Sullivan
AU  - Thomas Morley
AU  - Vincent M. Carroll
AU  - John Seibyl
AU  - Jianqing Chen
AU  - Chewah Lee
AU  - Anabella Villalobos
AU  - David Gray
AU  - Timothy J. McCarthy
AU  - Gilles Tamagnan
TI  - Dopamine D<sub>1</sub> Receptor Agonist PET Tracer Development: Assessment in Nonhuman Primates
AID  - 10.2967/jnumed.120.256008
DP  - 2021 Sep 01
TA  - Journal of Nuclear Medicine
PG  - 1307--1313
VI  - 62
IP  - 9
4099  - http://jnm.snmjournals.org/content/62/9/1307.short
4100  - http://jnm.snmjournals.org/content/62/9/1307.full
SO  - J Nucl Med2021 Sep 01; 62
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.