AI Article Synopsis
- The study evaluated [(18)F]PK-209 as a potential PET imaging ligand for the N-methyl-D-aspartate receptors (NMDArs), focusing on its selectivity and imaging capabilities.
- Dynamic PET scans were performed on male rhesus monkeys, both before and after administering MK-801, to assess the uptake and distribution of PK-209 in the brain.
- Results indicated that PK-209 showed strong selectivity for NMDArs, with significant radioactivity in NMDAr-rich regions, though its rapid metabolism suggests further human studies are necessary.
Article Abstract
Introduction: The present study was designed to assess whether [(18)F]PK-209 (3-(2-chloro-5-(methylthio)phenyl)-1-(3-([(18)F]fluoromethoxy)phenyl)-1-methylguanidine) is a suitable ligand for imaging the ion-channel site of N-methyl-D-aspartate receptors (NMDArs) using positron emission tomography (PET).
Methods: Dynamic PET scans were acquired from male rhesus monkeys over 120min, at baseline and after the acute administration of dizocilpine (MK-801, 0.3mg/kg; n=3/condition). Continuous and discrete arterial blood samples were manually obtained, to generate metabolite-corrected input functions. Parametric volume-of-distribution (VT) images were obtained using Logan analysis. The selectivity profile of PK-209 was assessed in vitro, on a broad screen of 79 targets.
Results: PK-209 was at least 50-fold more selective for NMDArs over all other targets examined. At baseline, prolonged retention of radioactivity was observed in NMDAr-rich cortical regions relative to the cerebellum. Pretreatment with MK-801 reduced the VT of [(18)F]PK-209 compared with baseline in two of three subjects. The rate of radioligand metabolism was high, both at baseline and after MK-801 administration.
Conclusions: PK-209 targets the intrachannel site with high selectivity. Imaging of the NMDAr is feasible with [(18)F]PK-209, despite its fast metabolism. Further in vivo evaluation in humans is warranted.
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| http://dx.doi.org/10.1016/j.nucmedbio.2014.09.006 | DOI Listing |
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