Radiosynthesis and In Vitro Evaluation of [18F]FE-MPC6827 as a Candidate PET Tracer for Imaging Microtubule Dynamics
7 affiliations
- 1Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Forschungszentrum Jülich GmbH, Wilhelm-Johnen-Straße, 52428 Jülich, Germany
- 2Institute of Radiochemistry and Experimental Molecular Imaging, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany
- 3Department of Nuclear Medicine, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany
- 4Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Straße 34, 50931 Cologne, Germany
- 5Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Straße 21, 50931 Cologne, Germany
- 6Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany
- 7Center for Human Genetics and Genomic Medicine, Medical Faculty, University Hospital RWTH Aachen, 52062 Aachen, Germany
Abstract
Microtubule (MT) dysfunction is a hallmark of neurodegenerative diseases, tauopathies, and genetic disorders. Positron emission tomography (PET) enables the non-invasive assessment of MT dynamics in vivo, but current 11C-labeled radiotracers are limited by the short half-life of carbon-11. Here, we report the radiosynthesis and in vitro evaluation of [18F]FE-MPC6827, an 18F-labeled derivative of the brain-penetrant MT-destabilizing agent MPC-6827 (verubulin). Radiosynthesis from the corresponding tosylate precursor afforded [18F]FE-MPC6827 in 60 ± 3% radiochemical yields (n = 22), >99% radiochemical purities, and molar activities up to 475 GBq/µmol. Physicochemical profiling revealed a logD7.4 value of 3.37 ± 0.05 and favorable CNS-MPO, BBB, and CNS-PET-MPO scores, although brain permeability remains to be established experimentally. In HEK293T cells, MT destabilization significantly increased tracer accumulation, whereas MT stabilization significantly reduced uptake. Overexpression of MT-associated proteins (tau, spastin, MARK, α-tubulin) produced directionally consistent but statistically non-significant changes in tracer uptake, concordant with its effects on MT mass or stability. Across the experiments, tracer uptake correlated inversely with the markers of MT stability. These findings suggest responsiveness to changes in MT organization, although preferential binding to depolymerized tubulin remains to be confirmed by direct binding studies. Taken together, [18F]FE-MPC6827 is a promising first-in-class radiofluorinated PET tracer candidate for imaging MT dynamics in the central nervous system.
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BibTeX
@article{gemki2026radiosynthesis,
title = {{Radiosynthesis and In Vitro Evaluation of [18F]FE-MPC6827 as a Candidate PET Tracer for Imaging Microtubule Dynamics}},
author = {Michael Gemki and Laura Wunderlich and Laura Köhler and Felix Neumaier and Heike Endepols and Boris D. Zlatopolskiy and Bernd Neumaier and Hans Zempel},
journal = {Cells},
year = {2026},
month = nov,
doi = {10.3390/cells15212033},
url = {https://www.mdpi.com/2073-4409/15/21/2033},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Radiosynthesis and In Vitro Evaluation of [18F]FE-MPC6827 as a Candidate PET Tracer for Imaging Microtubule Dynamics
AU - Michael Gemki
AU - Laura Wunderlich
AU - Laura Köhler
AU - Felix Neumaier
AU - Heike Endepols
AU - Boris D. Zlatopolskiy
AU - Bernd Neumaier
AU - Hans Zempel
PY - 2026
DA - 2026/11/07
JO - Cells
DO - 10.3390/cells15212033
UR - https://www.mdpi.com/2073-4409/15/21/2033
AB - Microtubule (MT) dysfunction is a hallmark of neurodegenerative diseases, tauopathies, and genetic disorders. Positron emission tomography (PET) enables the non-invasive assessment of MT dynamics in vivo, but current 11C-labeled radiotracers are limited by the short half-life of carbon-11. Here, we report the radiosynthesis and in vitro evaluation of [18F]FE-MPC6827, an 18F-labeled derivative of the brain-penetrant MT-destabilizing agent MPC-6827 (verubulin). Radiosynthesis from the corresponding tosylate precursor afforded [18F]FE-MPC6827 in 60 ± 3% radiochemical yields (n = 22), >99% radiochemical purities, and molar activities up to 475 GBq/µmol. Physicochemical profiling revealed a logD7.4 value of 3.37 ± 0.05 and favorable CNS-MPO, BBB, and CNS-PET-MPO scores, although brain permeability remains to be established experimentally. In HEK293T cells, MT destabilization significantly increased tracer accumulation, whereas MT stabilization significantly reduced uptake. Overexpression of MT-associated proteins (tau, spastin, MARK, α-tubulin) produced directionally consistent but statistically non-significant changes in tracer uptake, concordant with its effects on MT mass or stability. Across the experiments, tracer uptake correlated inversely with the markers of MT stability. These findings suggest responsiveness to changes in MT organization, although preferential binding to depolymerized tubulin remains to be confirmed by direct binding studies. Taken together, [18F]FE-MPC6827 is a promising first-in-class radiofluorinated PET tracer candidate for imaging MT dynamics in the central nervous system.
SN - 2073-4409
ER -