Introduction: For several decades, the 18kDa Translocator protein (TSPO) has been a molecular imaging target for inflammation. Recently, evidence has emerged indicating significant cardiovascular inflammatory events such as myocardial infarction (MI) can lead to subsequent neuroinflammation, all of which can be detected by targeting TSPO1. We have developed a novel TSPO ligand, LW223, which is the first fluorinated TSPO radiotracer with binding in human tissue independent of the rs6971 polymorphism. This study aims to assess the uptake of 18F-LW223 during MI using the rat permanent coronary artery ligation model. Methods: Adult male Sprague-Dawley rats were anaesthetised using 1.5-2.5% isoflurane (50/50 oxygen/nitrous oxide, 1 L/min) before undergoing permanent ligation of the left anterior descending artery to induce MI (n=6). On day 7, PET/CT imaging with 18F-LW223 was performed. Naive male Sprague-Dawley rats were used as a healthy control comparison (n=6). The standard uptake value relative to blood pool (SUVr) of 18F-LW223 in the heart, brain and lungs of MI and healthy controls were analysed using an unpaired t test. Sub regions of the heart were also analysed. Results are shown as mean ±SEM. Results: Day 7 PET imaging demonstrated a significant increase in 18F-LW223 SUVr within the infarcted whole myocardium vs. healthy (3.7± 0.4 vs. 2.0± 0.1 respectively, p=0.0020). The infarcted sub region of the MI hearts had a significantly lower SUVr than a comparable sub region in healthy animals (2.6± 0.4 vs. 4.4± 0.3 respectively, p=0.0071), which was expected due to decreased perfusion. The brains of MI animals had a significantly increased SUVr vs. healthy animals (0.8± 0.1 vs. 0.4± 0.03 respectively, p=0.0053, Fig. 1.B). Finally, the lungs of the MI animals also had increased uptake (4.9± 1.3 vs. 2.0± 0.1 respectively, p=0.0470). Conclusion: 18F-LW223 SUVr values are increased in the heart, brain and lungs at day 7 post myocardial infarction. Future efforts are now focussed on kinetic modelling of 18F-LW223 uptake in these animals using radiometabolite corrected arterial input functions.
Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, PC031
Poster Communications: In vivo non-invasive imaging of inflammation in a preclinical model of myocardial infarction using 18F-LW223 and Positron Emission Tomography
M. G. MacAskill1,2, N. Spath1, T. Walton1,2, L. Williams3, T. Morgan3, N. Sloan3, C. J. Alcaide-Corral1,2, W. Mungall1, M. R. Dweck1, G. Gray1, D. Newby1, C. Lucatelli2, A. Sutherland3, S. L. Pimlott4,5, A. A. Tavares1,2
1. University/ BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. 2. Edinburgh Imaging, University of Edinburgh, Edinburgh, United Kingdom. 3. School of Chemistry, University of Glasgow, Glasgow, United Kingdom. 4. School of Medicine, University of Glasgow, Glasgow, United Kingdom. 5. NHS Greater Glasgow and Clyde, Glasgow, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.