M A Stammes, M P M Vierboom, C C Sombroek, J Bakker, L Meijer, R A W Vervenne, S O Hofman, E Nutma, I Kondova, A D Windhorst, J A M Langermans, F A W Verreck
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引用次数: 0
Abstract
Purpose: Tuberculosis (TB) continues to afflict global health. Therefore, a deeper understanding of the host response mechanisms that underly pathogenesis versus disease control upon infection with Mycobacterium tuberculosis (Mtb) is required to leverage the development of improved therapeutic or prophylactic TB treatment regimens. In the present work positron emission tomography (PET) using [18F]DPA714 is piloted as a tracer of the mitochondrial translocator protein TSPO that mainly targets macrophages.
Procedures: We compared two tracers: [18F]DPA714 to the widely applied marker [18F]FDG to visualize the development of experimental pulmonary TB in three rhesus monkeys (Macaca mulatta), that were infected with Mtb by repeated low dose exposure. Next to baseline recordings prior to infectious challenge, two PETs at a two-weeks interval were acquired early after the manifestation of TB infection for each of the respective tracers.
Results & conclusions: Here, we demonstrate that both PET tracers detected Mtb infection. The inflammatory response tracked by [18F]FDG progressively increased in line with the developing TB pathology, while [18F]DPA714 showed a transient signal in lungs and lung-draining hilar lymph nodes. This study underpins the potential value of different tracers to investigate cellular and molecular host response cascades in experimental medicine settings, in this case, into a (transient) local involvement of myeloid immune cell activation versus inflammation-associated glucose consumption in pulmonary TB.
期刊介绍:
Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures.
Some areas that are covered are:
Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes.
The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets.
Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display.
Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging.
Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics.
Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations.
Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.