• Shock · Oct 2015

    T-14: IN VIVO IMAGING OF NEUROINFLAMMATION IN NEUROTRAUMA PRECLINICAL MODELS: POTENTIAL FOR CLINICAL TRANSLATION.

    • J L Tremoleda, O Thau-Zuchman, M Davies, J Foster, I Khan, W Trigg, J Sosabowski, S J Mather, and A Michael-Titus.
    • 1Centre for Trauma Sciences, QMUL, London, UK 2Barts Cancer Institute, QMUL, London, UK 3GE-Heatlhcare Ltd, Amersham, UK.
    • Shock. 2015 Oct 1;44 Suppl 2:24-5.

    IntroductionThe development of clinically meaningful biomarkers for CNS traumatic injury is a major area in neurotrauma modelling. Neuroimaging is evolving as a major approach to characterize pathophysiology, improve diagnosis and test new therapies. Imaging the microglial response by targeting the up- regulation of the 18 kDa translocator protein (TSPO) following CNS injury, is a main diagnostic approach for investigating the neuroinflammatory (NI) response after CNS injury in vivo.MethodsWe investigated the use of TSPO selective PET and SPECT ligands to image the NI response in two experimental neurotrauma models. A controlled cortical impact was used to induce traumatic brain injury (TBI) in adult mice and SPECT/CT imaging was carried out at day 7 post-injury using the [123I]-CLINDE SPECT TSPO radiotracer. A controlled contusion spinal cord injury (SCI) at thoracic T10 level was performed in adult rats (n = 8) and PET/CT imaging was carried out at day 7 post-injury using the GE-180 TSPO PET radiotracer.ResultsClinical PET imaging provides higher spatial resolution and hence better suitability for imaging SCI. Differential radioactivity uptake in vivo was detected and quantified in the injured tissue, around the primary injury site, in both injury models, compared to sham-non CNS injured animals (TBI %ID/gr: injured right hemisphere 0.022 ± 0.001 vs. naïve right hemisphere 0.01 ± 0.0001, Fig. 1A; SCI %ID/gr T10 spinal cord area: 0.5 ± 0.05 SCI vs. 0.3 ± 0.07 laminectomy vs. 0.2 ± 0.003 naïve non-injured, Fig. 1B; P < 0.001; ANOVA). Specific TSPO ligand binding was confirmed by ex vivo biodistribution and autoradiography of injured tissue. Immunocytochemistry analysis of the tissue is on-going, to further characterise the TSPO signal and differentiate between resident microglia and infiltrating peripherally-derived macrophages.(Figure is included in full-text article.)Conclusion: This study shows the significant potential of these imaging tracers as sensitive clinical tools for non- invasive monitoring of the NI response and, potentially, of the response of NI to new therapies.

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