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

摘要

id="p-2">11C-(+)-4-propyl-9-hydroxynaphthoxazine (11C-(+)-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 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 (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 11C-(+)-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 (a?’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.