Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and [18F]deuteroaltanserin

Abstract The test/retest reproducibility of brain measures of 5-HT2A receptors with positron emission tomography (PET) and [ 18 F]deuteroaltanserin was examined in a group of eight healthy human subjects. PET measures of 5-HT2A receptors were obtained under an equilibrium paradigm, with a 40-min PET acquisition starting approximately at 300 min (308±11 min) after bolus plus constant infusion of the radiotracer. Three brain outcome measures were obtained at equilibrium, V 3 (ratio of specific brain uptake to free parent plasma concentration of radiotracer), V 3 ′ (ratio of specific brain uptake to total parent plasma concentration) and RT (ratio of specific to non-displaceable brain uptakes). V 3 ′ and RT had high test/retest reproducibility, as measured by mean intra-subject% change for cortical brain areas of 14.1 and 11.0%, respectively. They also had high reliability, as measured by mean intra-class correlation coefficients (ICC) for cortical brain areas of 0.86 and 0.88, respectively. V 3 had low test/retest reproducibility, due to high variability in the measures of free parent tracer in plasma. This study supports the feasibility of equilibrium imaging of 5-HT2A receptors with PET and [ 18 F]deuteroaltanserin. The equilibrium imaging method with [ 18 F]deuteroaltanserin allows a single acquisition and blood measurement to provide an image whose pixel values equal a receptor volume of distribution. Since the single image pixel values are proportional to receptor densities, the images can be used in pixel-by-pixel statistical methods, such as SPM, to assess the distribution and density of 5-HT2A receptors in neuropsychiatric disorders.