Abstract
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Objectives Despite their importance the k-opioid receptors have not been sistematically studied with PET.We employed a recently developed k-agonist tracer([11C]GR103545) and performed a Scatchard study in order to estimate the in vivo receptor concentration Bmax and the dissociation constant Kd.
Methods Three rhesus monkeys were scanned with the FOCUS 220:2 of them underwent 2 scans(baseline+self-block), the third was scanned 4 times (2 baseline and 2 self-block at different occupancy levels). A Bolus+Infiusion (B/I) protocol was employed and the cerebellum was used as reference region. Injected masses were 0.042±0.014 ug/Kg at baseline and ranged from 0.17 to 0.3 ug/Kg fro the self-block studies. BPND of all ROIs was computed as [(CROI / CCEREB) -1], CROI and CCEREB being the mean radioactivity concentration from 90 to 120 min in each ROI and in the cerebellum. A standard Scatchard plot was then used to estimate Bmax and Kd,ND=Kd/fND. When Kd,ND was allowed to vary among ROIs, results were very variable; therefore Kd,ND was constrained to be constant across ROIs.
Results Bmax ranged from 2 nM to 8 nM with a peak of 15 nM in the putamen; high values were obtained also in cingulate, globus pallidus and insula.Kd,ND was estimated to be 5.85 nM. In addition, Kd, computed as Kd,NDfND was 0.16nM (based on estimates of VND and fP) in good agreement with the in vitro Ki value of 0.33 nM. Percentage standard errors (%SE) were high (>100%) partly due to large intersubject variability.
Conclusions The use of a B/I protocol with the k-opioid agonist tracer [11C]GR103545 permitted succesful estimation of Bmax and Kd,ND in vivo.
- © 2009 by Society of Nuclear Medicine