Abstract
1903
Objectives To demonstrate the competitive effect of PK11195 on the uptake of PBR ligands fluoroethoxy ([18F]PBR102) and fluoropropoxy ([18F]PBR111) substituted 2-(6-chloro-2-phenyl)imidazo[1,2-a]pyridine-3-yl)-N,N-diethylacetamides in rats and baboons.
Methods Rats injected with [18F]PBR102 and [18F]PBR111 were sacrificed at 1hr and 2hr p.i. PK11195 (1mg/kg) was injected 5 min before (pre-blocking) or 1 hr (displacement) after radiotracer injection. Tissue radioactivity concentration of treated rats was compared to controls. PET-CT dynamic brain studies in baboons were performed with both tracers injected at baseline followed by displacement with PK11195 (5 mg/kg) at 30-40min.
Results In treated rats, [18F]PBR102 and [18F]PBR111 uptake in peripheral organs, bone marrow and olfactory bulbs was 60-90% lower than controls. The higher brain uptake was explained by the increased tracer concentration in blood. In baboons, displacement by PK11195 increased the metabolite corrected plasma tracer concentration of the tracers. Displacement was pronounced in the bone marrow region for PBR102, but was attenuated for PBR111 due to 18F-fluoride bone uptake. The small displacement in the brain is consistent with the low concentration of PBR receptors.
Conclusions Competition studies demonstrated that PK11195 can inhibit or displace uptake of the two novel [18F]PBR102 and [18F]PBR111 ligands in peripheral organs and in the brain. Brain uptake is consistent with low concentration of PBR receptors in the brain versus peripheral organs and requires careful consideration of the influence of plasma tracer concentration.
- © 2009 by Society of Nuclear Medicine