Knyzeliene, A., Wimberley, C., MacAskill, M. G., Alcaide-Corral, C. J., Morgan, T. E. F., Henry, M. C., Lucatelli, C., Pimlott, S. L. , Sutherland, A. and Tavares, A. A. S. (2024) Sexually dimorphic murine brain uptake of the 18 kDa translocator protein PET radiotracer [18F]LW223. Brain Communications, fcae008. (doi: 10.1093/braincomms/fcae008) (In Press)
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Abstract
The 18 kDa translocator protein is a well-known biomarker of neuroinflammation, but also plays a role in homeostasis. Positron Emission Tomography (PET) with 18 kDa translocator protein radiotracers [11C]PBR28 in humans and [18F]GE180 in mice have demonstrated sex-dependent uptake patterns in the healthy brain, suggesting sex-dependent 18 kDa translocator protein expression, although humans and mice had differing results. This study aimed to assess whether the 18 kDa translocator protein PET radiotracer [18F]LW223 exhibited sexually-dimorphic uptake in healthy murine brain and peripheral organs. Male and female C57Bl6/J mice (13.6 ± 5.4 weeks, 26.8 ± 5.4 g, mean ± SD) underwent 2-hour PET scanning post-administration of [18F]LW223 (6.7 ± 3.6 MBq). Volume of interest and parametric analyses were performed using standard uptake values (90-120 min). Statistical differences were assessed by unpaired t-test or two-way ANOVA with Šidak’s test (alpha = 0.05). The uptake of [18F]LW223 was significantly higher across multiple regions of the male mouse brain, with the most pronounced difference detected in hypothalamus (p < 0.0001). Males also exhibited significantly higher [18F]LW223 uptake in the heart when compared to females (p = 0.0107). Data supports previous findings on sexually dimorphic 18 kDa translocator protein radiotracer uptake patterns in mice and highlights the need to conduct sex-controlled comparisons in 18 kDa translocator protein PET imaging studies.
| Item Type: | Articles |
|---|---|
| Additional Information: | 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 Engineering and Physical Sciences Research Council PhD studentship (EP/M508056/1). AAST is a recipient of a Wellcome Trust Technology Development Award (221295/Z/20/Z). This paper has been made possible in part by a Chan Zuckerberg Initiative DAF grant number 2020-225273, an advised fund of Silicon Valley Community Foundation (https://doi.org/10.37921/690910twdfoo). CA-C and CL are supported by Edinburgh Imaging. |
| Keywords: | Neurology, Cellular and Molecular Neuroscience, Biological Psychiatry, Psychiatry and Mental health |
| Status: | In Press |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Pimlott, Dr Sally and Henry, Mr Martyn |
| Authors: | Knyzeliene, A., Wimberley, C., MacAskill, M. G., Alcaide-Corral, C. J., Morgan, T. E. F., 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: | Brain Communications |
| Publisher: | Oxford University Press |
| ISSN: | 2632-1297 |
| ISSN (Online): | 2632-1297 |
| Published Online: | 16 January 2024 |
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