MacAskill, M. G., Wimberley, C., Morgan, T. E. F., Alcaide‑Corral, C. J., Newby, D. E., Lucatelli, C., Sutherland, A. , Pimlott, S. L. and Tavares, A. A. S. (2021) Modelling [18F]LW223 PET data using simplified imaging protocols for quantification of TSPO expression in the rat heart and brain. European Journal of Nuclear Medicine and Molecular Imaging, 49, pp. 137-145. (doi: 10.1007/S00259-021-05482-1) (PMID:34338808) (PMCID:PMC8712302)
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Abstract
Purpose: To provide a comprehensive assessment of the novel 18 kDa translocator protein (TSPO) radiotracer, [18F]LW223, kinetics in the heart and brain when using a simplified imaging approach. Methods: Naive adult rats and rats with surgically induced permanent coronary artery ligation received a bolus intravenous injection of [18F]LW223 followed by 120 min PET scanning with arterial blood sampling throughout. Kinetic modelling of PET data was applied to estimated rate constants, total volume of distribution (VT) and binding potential transfer corrected (BPTC) using arterial or image-derived input function (IDIF). Quantitative bias of simplified protocols using IDIF versus arterial input function (AIF) and stability of kinetic parameters for PET imaging data of different length (40–120 min) were estimated. Results: PET outcome measures estimated using IDIF significantly correlated with those derived with invasive AIF, albeit with an inherent systematic bias. Truncation of the dynamic PET scan duration to less than 100 min reduced the stability of the kinetic modelling outputs. Quantification of [18F]LW223 uptake kinetics in the brain and heart required the use of different outcome measures, with BPTC more stable in the heart and VT more stable in the brain. Conclusion: Modelling of [18F]LW223 PET showed the use of simplified IDIF is acceptable in the rat and the minimum scan duration for quantification of TSPO expression in rats using kinetic modelling with this radiotracer is 100 min. Carefully assessing kinetic outcome measures when conducting a systems level as oppose to single-organ centric analyses is crucial. This should be taken into account when assessing the emerging role of the TSPO heart-brain axis in the field of PET imaging.
| Item Type: | Articles |
|---|---|
| Additional Information: | Funding: This work was funded by the British Heart Foundation (PG/16/12/32022 and PG/17/83/33370) and the Engineering and Physical Sciences Research Council (EPSRC Impact Acceleration Awards, EP/K5039031 and EP/R511705/1). The British Heart Foundation is greatly acknowledged for providing funding towards establishment of the preclinical PET/CT laboratory at the University of Edinburgh (RE/13/3/30183) and radiometabolite laboratories (RG/16/10/32375). AAST, TEFM and MGM are funded by the British Heart Foundation (RG/16/10/32375, FS/19/34/34354). AAST is a recipient of a Wellcome Trust Technology Development Award (221295/Z/20/Z). MGM was also funded by the British Heart Foundation (PG/16/12/32022, PG/17/83/33370). DEN is funded by the British Heart Foundation (CH/09/002, RG/16/10/32375, RE/18/5/34216) and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). CA-C and CL are supported by the Edinburgh Preclinical Imaging and Edinburgh Imaging core facilities, respectively. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Pimlott, Dr Sally and Sutherland, Professor Andrew |
| Authors: | MacAskill, M. G., Wimberley, C., Morgan, T. E. F., Alcaide‑Corral, C. J., Newby, D. E., Lucatelli, C., Sutherland, A., Pimlott, S. L., 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: | European Journal of Nuclear Medicine and Molecular Imaging |
| Publisher: | Springer |
| ISSN: | 1619-7070 |
| ISSN (Online): | 1619-7089 |
| Published Online: | 02 August 2021 |
| Copyright Holders: | Copyright © The Author(s) 2021 |
| First Published: | First published in European Journal of Nuclear Medicine and Molecular Imaging 49: 137-145 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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