Tracer Kinetic Modeling of the 5-HT1AReceptor Ligand [carbonyl-11C]WAY-100635 for PET

Serotonin 5-HT1A Receptor Binding Potential Declines with Age as Measured by [11C]WAY-100635 and PET

“…After injection of 9.56 mCi ( Ϯ .77 [SD]) [ 11 C]WAY-100635, ROI analysis of 60 minutes TAC by means of a simplified reference tissue method (Gunn et al 1998) yielded 5-HT 1A BP values (mean Ϯ SD) ranging from 5.10 ( Ϯ 0.69) in MTC to 2.10 ( Ϯ 0.65) in the raphe nuclei (Table 1) Volume of interest (VOI) values ranged from 54.4 cm 3 in parietel cortex to 0.6 cm 3 for the raphe nuclei (Table 1). There was no correlation of age and VOI size in most ROI and in the cerebellum, with the exception of the occipital cortex (r ϭ 0.52; p ϭ .026) and OFC (r ϭ Ϫ0.66; p ϭ .002).…”

“…Regional binding potential (BP) values were calculated to estimate the 5-HT 1A receptor number in each ROI (Mintun et al 1984). To obtain BP values, the cerebellum was used as the input function of a simplified reference tissue method, because the cerebellum is relatively devoid of 5-HT 1A receptors (Burnet et al 1997) and this method proved to be superior to kinetic modeling using arterial data (Gunn et al 1998).…”

Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

“…In some studies with [ 11 C ]WAY (Rabiner et al, 2002;Doder et al, 2003;Turner et al, 2005), as many as 10% of the subjects were excluded because of abnormally high cerebellar time-activity curves potentially caused by specific binding in cerebellum, incorrect segmentation of cerebellum, or variable properties of the tracer. One of the known properties of [ 11 C]WAY is the very rapid metabolism in the circulation (Gunn et al, 1998;Osman et al, 1998), which may violate the underlying assumption of continuous exchange of brain tissue with circulation and thereby may induce biases to the results of previously applied kinetic models.…”

“…Using cerebellum as reference region, average uptakes in ROIs were also analyzed by the Logan et al, SRTM (Gunn et al, 1998;Lammertsma and Hume, 1996) and ERliBiRD methods (Rosa-Neto et al, 2004). The ERLiBiRD method fits the following Equation…”

“…Thus, normal aging showed significant decline of cortical [ 11 C]WAY binding in one study of rhesus monkeys (Tsukada et al, 2001) and three studies of humans (Tauscher et al, 2001;Cidis Meltzer et al, 2001;Bhagwagar et al, 2004), where as no correlation with age was reported in two other studies of humans (Parsey et al, 2002;Rabiner et al, 2002). In addition, the findings may reflect problems with kinetic analysis of binding due to the very rapid metabolism of the tracer in the circulation (Gunn et al, 1998;Osman et al, 1998) and the reported high inter-subject variability in [ 11 C]WAY binding, as demonstrated in a large cohort of healthy male subjects. The study found no correlation between pB and demographics, physiological or behavioral variables or levels of endogenous serotonin (Rabiner et al, 2002).…”