Parametric imaging and test-retest variability of11C-(+)-PHNO binding to D2/D3 dopamine receptors in humans on the high-resolution research tomograph PET scanner

Abstract

11C-(+)-4-propyl-9-hydroxynaphthoxazine (11C-(+)- PHNO) is an agonist radioligand for imaging dopamine D2 and D 3 receptors in the humanbrain with PET. In this studyweevaluated the reproducibility of 11C-(+)-PHNO binding parameters using a within-day design and assessed parametric imaging methods. Methods: Repeated studies were performed in 8 subjects, with simultaneous measurement of the arterial input function and plasma free fraction. Two 11C-(+)-PHNO scans for the same subject were separated by 5.4 ± 0.7 h. After compartment models were evaluated, 11C-(+)-PHNO volumes of distribution (VT) and binding potentials relative to the concentration of tracer in plasma (BPP), nondisplaceable tracer in tissue (BPND), and free tracer intissue (BPF) were quantified using the multilinear analysis MA1 method, with the cerebellum as the reference region. Parametric images of BPND were also computed using the simplified reference tissue model (SRTM) and SRTM2. Results: The test-retest variability of 11C-(+)-PHNO BPND was 9% in D2-rich regions (caudate and putamen). Among D 3-rich regions, variability was low in the pallidum (6%) but higher in substantia nigra (19%), thalamus (14%), and hypothalamus (21%). No significant mass carry-over effect was observed in D3-rich regions, although a trend in BPND was present in the substantia nigra (-14% ± 15%). Because of the relatively fast kinetics, low-noise BP ND parametric images were obtained with both SRTM and SRTM2 without spatial smoothing. Conclusion: 11C-(+)-PHNO can be used to compute low-noise parametric images in both D2- and D3-rich regions in humans. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.