Parametric Imaging and Test-Retest Variability of ¹¹C-(+)-PHNO Binding to D₂/D₃ Dopamine Receptors in Humans on the High-Resolution Research Tomograph PET Scanner

(11)C-(+)-4-propyl-9-hydroxynaphthoxazine ((11)C-(+)-PHNO) is an agonist radioligand for imaging dopamine D2 and D3 receptors in the human brain with PET. In this study we evaluated the reproducibility of (11)C-(+)-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 (11)C-(+)-PHNO scans for the same subject were separated by 5.4 ± 0.7 h. After compartment models were evaluated, (11)C-(+)-PHNO volumes of distribution (V(T)) and binding potentials relative to the concentration of tracer in plasma (BP(P)), nondisplaceable tracer in tissue (BP(ND)), and free tracer in tissue (BP(F)) were quantified using the multilinear analysis MA1 method, with the cerebellum as the reference region. Parametric images of BP(ND) were also computed using the simplified reference tissue model (SRTM) and SRTM2.

Results: The test-retest variability of (11)C-(+)-PHNO BP(ND) was 9% in D2-rich regions (caudate and putamen). Among D3-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 BP(ND) 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: (11)C-(+)-PHNO can be used to compute low-noise parametric images in both D2- and D3-rich regions in humans.