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EJNMMI Research
Published in: EJNMMI Research 1/2018

Open Access 01-12-2018 | Original research

First in human evaluation of [18F]PK-209, a PET ligand for the ion channel binding site of NMDA receptors

Authors: Jasper van der Aart, Sandeep S. V. Golla, Marieke van der Pluijm, Lothar A. Schwarte, Robert C. Schuit, Pieter J. Klein, Athanasios Metaxas, Albert D. Windhorst, Ronald Boellaard, Adriaan A. Lammertsma, Bart N. M. van Berckel

Published in: EJNMMI Research | Issue 1/2018

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Abstract

Background

Efforts to develop suitable positron emission tomography (PET) tracers for the ion channel site of human N-methyl-d-aspartate (NMDA) receptors have had limited success. [18F]PK-209 is a GMOM derivative that binds to the intrachannel phencyclidine site with high affinity and selectivity. Primate PET studies have shown that the volume of distribution in the brain was reduced by administration of the NMDA receptor antagonist MK-801, consistent with substantial specific binding. The purpose of the present study was to evaluate [18F]PK-209 in 10 healthy humans by assessing test–retest reproducibility and binding specificity following intravenous S-ketamine administration (0.5 mg ∙ kg−1). Five healthy subjects underwent a test–retest protocol, and five others a baseline-ketamine protocol. In all cases dynamic, 120-min PET scans were acquired together with metabolite-corrected arterial plasma input functions. Additional input functions were tested based on within-subject and population-average parent fractions.

Results

Best fits of the brain time-activity curves were obtained using an irreversible two-tissue compartment model with additional blood volume parameter. Mean test–retest variability of the net rate of influx Ki varied between 7 and 24% depending on the input function. There were no consistent changes in [18F]PK-209 PET parameters following ketamine administration, which may be a consequence of the complex endogenous ligand processes that affect channel gating.

Conclusions

The molecular interaction between [18F]PK-209 and the binding site within the NMDA receptor ion channel is insufficiently reproducible and specific to be a reliable imaging agent for its quantification.

Trial registration

EudraCT 2014-001735-36. Registered 28 April 2014
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Metadata
Title
First in human evaluation of [18F]PK-209, a PET ligand for the ion channel binding site of NMDA receptors
Authors
Jasper van der Aart
Sandeep S. V. Golla
Marieke van der Pluijm
Lothar A. Schwarte
Robert C. Schuit
Pieter J. Klein
Athanasios Metaxas
Albert D. Windhorst
Ronald Boellaard
Adriaan A. Lammertsma
Bart N. M. van Berckel
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2018
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-018-0424-2

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