In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease

18 kDa 转位蛋白 (TSPO) 在炎症性血管疾病中的体外和初步体内成像

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Abstract

BACKGROUND: Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [(11)C]-PBR28 and [(18)F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [(18)F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [(18)F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [(11)C]-PBR28. RESULTS: All in vitro sections showed specific binding of [(18)F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [(11)C]-PBR28 or [(18)F]-PBR06 was negative in all participants. CONCLUSION: Despite good uptake on surgical samples in vitro, [(11)C]-PBR28 and [(18)F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease. TRIAL REGISTRATION: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov .

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