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结核病的分子成像

Molecular Imaging of Tuberculosis.

作者信息

Lawal Ismaheel O, Abubakar Sofiullah, Ankrah Alfred O, Sathekge Mike M

机构信息

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA; Department of Nuclear Medicine, University of Pretoria, Pretoria, Gauteng, South Africa.

Department of Radiology and Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center, Muscat, Oman.

出版信息

Semin Nucl Med. 2023 Jan;53(1):37-56. doi: 10.1053/j.semnuclmed.2022.07.001. Epub 2022 Jul 23.

Abstract

Despite the introduction of many novel diagnostic techniques and newer treatment agents, tuberculosis (TB) remains a major cause of death from an infectious disease worldwide. With about a quarter of humanity harboring Mycobacterium tuberculosis, the causative agent of TB, the current efforts geared towards reducing the scourge due to TB must be sustained. At the same time, newer alternative modalities for diagnosis and treatment response assessment are considered. Molecular imaging entails the use of radioactive probes that exploit molecular targets expressed by microbes or human cells for imaging using hybrid scanners that provide both anatomic and functional features of the disease being imaged. Fluorine-18 fluorodeoxyglucose (FDG) is the most investigated radioactive probe for TB imaging in research and clinical practice. When imaged with positron emission tomography interphase with computed tomography (PET/CT), FDG PET/CT performs better than sputum conversion for predicting treatment outcome. At the end of treatment, FDG PET/CT has demonstrated the unique ability to identify a subset of patients declared cured based on the current standard of care but who still harbor live bacilli capable of causing disease relapse after therapy discontinuation. Our understanding of the pathogenesis and evolution of TB has improved significantly in the last decade, owing to the introduction of FDG PET/CT in TB research. FDG is a non-specific probe as it targets the host inflammatory response to Mycobacterium tuberculosis, which is not specifically different in TB compared with other infectious conditions. Ongoing efforts are geared towards evaluating the utility of newer probes targeting different components of the TB granuloma, the hallmark of TB lesions, including hypoxia, neovascularization, and fibrosis, in TB management. The most exciting category of non-FDG PET probes developed for molecular imaging of TB appears to be radiolabeled anti-tuberculous drugs for use in studying the pharmacokinetic characteristics of the drugs. This allows for the non-invasive study of drug kinetics in different body compartments concurrently, providing an insight into the spatial heterogeneity of drug exposure in different TB lesions. The ability to repeat molecular imaging using radiolabeled anti-tuberculous agents also offers an opportunity to study the temporal changes in drug kinetics within the different lesions during treatment.

摘要

尽管引入了许多新型诊断技术和更新的治疗药物,但结核病仍然是全球传染病死亡的主要原因。约四分之一的人感染结核分枝杆菌(结核病的病原体),因此必须持续目前为减少结核病祸害所做的努力。与此同时,人们正在考虑用于诊断和治疗反应评估的更新替代方法。分子成像需要使用放射性探针,这些探针利用微生物或人类细胞表达的分子靶点,通过提供所成像疾病的解剖和功能特征的混合扫描仪进行成像。氟-18氟脱氧葡萄糖(FDG)是研究和临床实践中用于结核病成像研究最多的放射性探针。当与计算机断层扫描(PET/CT)进行正电子发射断层扫描成像时,FDG PET/CT在预测治疗结果方面比痰菌转阴表现更好。在治疗结束时,FDG PET/CT已显示出独特的能力,能够识别出根据当前护理标准被宣布治愈但仍携带活细菌、在治疗中断后可能导致疾病复发的一部分患者。在过去十年中,由于在结核病研究中引入了FDG PET/CT,我们对结核病发病机制和演变的理解有了显著提高。FDG是一种非特异性探针,因为它针对宿主对结核分枝杆菌的炎症反应,而这种反应在结核病中与其他感染情况相比并无特异性差异。目前正在努力评估针对结核结节不同成分(结核病病变的标志,包括缺氧、新生血管形成和纤维化)的新型探针在结核病管理中的效用。为结核病分子成像开发的最令人兴奋的非FDG PET探针类别似乎是用于研究药物药代动力学特征的放射性标记抗结核药物。这使得能够同时对不同身体部位的药物动力学进行非侵入性研究,深入了解不同结核病变中药物暴露的空间异质性。使用放射性标记抗结核药物重复进行分子成像的能力也提供了一个机会,来研究治疗期间不同病变内药物动力学的时间变化。

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