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18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response.

ABSTRACT: Development of antiviral therapy against acute viral diseases, such as dengue virus (DENV), suffers from the narrow window of viral load detection in serum during onset and clearance of infection and fever. We explored a biomarker approach using 18F-fluorodeoxyglucose (18F-FDG) PET in established mouse models for primary and antibody-dependent enhancement infection with DENV. 18F-FDG uptake was most prominent in the intestines and correlated with increased virus load and proinflammatory cytokines. Furthermore, a significant temporal trend in 18F-FDG uptake was seen in intestines and selected tissues over the time course of infection. Notably, 18F-FDG uptake and visualization by PET robustly differentiated treatment-naive groups from drug-treated groups as well as nonlethal from lethal infections with a clinical strain of DENV2. Thus, 18F-FDG may serve as a novel DENV infection-associated inflammation biomarker for assessing treatment response during therapeutic intervention trials.

SUBMITTER: Chacko AM

PROVIDER: S-EPMC5414563 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response.

Chacko Ann-Marie AM Watanabe Satoru S Herr Keira J KJ Kalimuddin Shirin S Tham Jing Yang JY Ong Joanne J Reolo Marie M Serrano Raymond Mf RM Cheung Yin Bun YB Low Jenny Gh JG Vasudevan Subhash G SG

JCI insight 20170504 9

Development of antiviral therapy against acute viral diseases, such as dengue virus (DENV), suffers from the narrow window of viral load detection in serum during onset and clearance of infection and fever. We explored a biomarker approach using 18F-fluorodeoxyglucose (18F-FDG) PET in established mouse models for primary and antibody-dependent enhancement infection with DENV. 18F-FDG uptake was most prominent in the intestines and correlated with increased virus load and proinflammatory cytokine ...[more]

PMID: 28469088

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Project description:BACKGROUND:Stress exposure can significantly affect serotonergic signaling with a particular impact on 5-HT1A receptor expression. Positron emission tomography (PET) provides opportunities for molecular imaging of alterations in 5-HT1A receptor binding following stress exposure. Considering the possible role of 5-HT1A receptors in stress coping mechanisms, respective imaging approaches are of particular interest. MATERIAL AND METHODS:For twelve consecutive days, Sprague Dawley rats were exposed to daily transport with a 1?h stay in a laboratory or daily transport plus 1?h restraint in a narrow tube. Following, animals were subjected to ?PET imaging with 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[18F]fluoro-benzamidoethylpiperazine ([18F]MPPF) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). Behavioral and biochemical parameters were analyzed to obtain additional information. RESULTS:In rats with repeated transport, hippocampal [18F]MPPF binding exceeded that in the naive group, while no difference in [18F]FDG uptake was detected between the groups. A transient decline in body weight was observed in rats with transport or combined transport and restraint. Thereby, body weight development correlated with [18F]MPPF binding. CONCLUSIONS:Mild-to-moderate stress associated with daily transport and exposure to a laboratory environment can trigger significant alterations in hippocampal binding of the 5-HT1A receptor ligand [18F]MPPF. This finding indicates that utmost care is necessary to control and report transport and associated handling procedures for animals used in ?PET studies analyzing the serotonergic system in order to enhance the robustness of conclusions and allow replicability of findings. In view of earlier studies indicating that an increase in hippocampal 5-HT1A receptor expression may be associated with a resilience to stress, it would be of interest to further evaluate 5-HT1A receptor imaging approaches as a candidate biomarker for the vulnerability to stress.

Dataset Information

18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response.

Publications

18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response.

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