Molecular Imaging Approaches to the Evaluation of Infectious Diseases- A Prospective Assessment
USAMRIID Frederick United States
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Molecular imaging, primarily defined as nuclear and optical imaging have been used extensively in neuroscience, cardiovascular, inflammation and oncology research to evaluate disease progression and drug intervention. Opportunities exist to extend the use of the tools developed for the above disease areas into infectious diseases caused by lethal and debilitating BSL34 pathogens such as alphaviruses and filoviruses. Virus distribution and replication can be monitored in animal models preclinically using reengineered pathogens containing nuclear or optical bioreporters. Use of the bioreporters will establish the tissue burden of virus, provide a means of assessing the effect of direct antiviral agents on pathogen replication and identify reservoirs of virus that may appear late in the disease that are left unaffected by drug therapy. Measuring tissue viral levels by imaging more directly assesses the degree of infection and when related to tissue levels of a PET radiolabeled drug, a relationship between plasma and tissue drug and virus levels can be established to better direct therapeutic intervention. The consequences of infection can be assessed dynamically using specific PETSPECT tracers developed to assess inflammation, hypoxia, metabolism, perfusion, apoptosis, hemorrhage and end organ damage. Colocalization of radiolabeled drug, virus and changes in tissue function can be used to define the stage of disease progression, monitor drug efficacy and allow for a greater mechanistic understanding of the viral infection. Given the sensitivity and specificity of molecular imaging approaches, coupling measures of viral load, tissue response and proteomic and genomic biomarker approaches may better define markers of BSL34 infection and disease progression.