Knyzeliene, A., MacAskill, M. G., Alcaide-Corral, C. J., Morgan, T. E., Henry, M. C., Lucatelli, C., Pimlott, S. L. , Sutherland, A. and Tavares, A. A.S. (2023) [18F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging. Journal of Cerebral Blood Flow and Metabolism, (doi: 10.1177/0271678x231205661) (PMID:37795635) (Early Online Publication)
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Abstract
Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [18F]LW223, in mice and specifically assess its volume of non-displaceable binding (VND) in brain as well as investigate the use of simplified analysis approaches for quantification of [18F]LW223 PET data. Adult male mice were injected with [18F]LW223 and varying concentrations of LW223 (0.003–0.55 mg/kg) to estimate VND of [18F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values (SUV) and apparent volume of distribution (VTapp), were investigated. [18F]LW223 had low VND in the brain (<10% of total binding) and low radiometabolism (∼15–20%). The 2-tissue compartment model provided the best fit for [18F]LW223 PET data, although its correlation with SUV90–120min or VTapp allowed for [18F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [18F]LW223 has the required properties to become a successful TSPO PET radiotracer.
| Item Type: | Articles |
|---|---|
| Additional Information: | The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the British Heart Foundation (RE/13/3/30183, RG/16/10/32375). AK studentship was supported by a Principal’s Career Development Award. AAST, TEFM and MGM are funded by the British Heart Foundation (RG/16/10/32375, FS/19/34/34354). MCH was funded by an EPSRC PhD studentship (EP/M508056/1). AAST is a recipient of a Wellcome Trust Technology Development Award (221295/Z/20/Z) and a Chan Zuckerberg Initiative DAF grant number 2020-225273, an advised fund of Silicon Valley Community Foundation (grant DOI: https://doi.org/10.37921/690910twdfoo). CA-C and CL are supported by Edinburgh Imaging. |
| Keywords: | Cardiology and Cardiovascular Medicine, Neurology (clinical), Neurology |
| Status: | Early Online Publication |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Pimlott, Dr Sally and Henry, Mr Martyn and Sutherland, Professor Andrew |
| Authors: | Knyzeliene, A., MacAskill, M. G., Alcaide-Corral, C. J., Morgan, T. E., Henry, M. C., Lucatelli, C., Pimlott, S. L., Sutherland, A., and Tavares, A. A.S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing College of Science and Engineering > School of Chemistry |
| Journal Name: | Journal of Cerebral Blood Flow and Metabolism |
| Publisher: | Nature Publishing Group |
| ISSN: | 0271-678X |
| ISSN (Online): | 1559-7016 |
| Published Online: | 05 October 2023 |
| Copyright Holders: | Copyright: © The Author(s) 2023 |
| First Published: | First published in Journal of Cerebral Blood Flow and Metabolism 2024 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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