Dataset Information

¹²⁴I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection.

ABSTRACT:

Purpose

Molecular imaging has provided unparalleled opportunities to monitor disease processes, although tools for evaluating infection remain limited. Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by lung injury that we sought to model. Activated macrophages/phagocytes have an important role in lung injury, which is responsible for subsequent respiratory failure and death. We performed pulmonary PET/CT with ¹²⁴I-iodo-DPA-713, a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by activated macrophages cells, to evaluate the local immune response in a hamster model of SARS-CoV-2 infection.

Procedures

Pulmonary ¹²⁴I-iodo-DPA-713 PET/CT was performed in SARS-CoV-2-infected golden Syrian hamsters. CT images were quantified using a custom-built lung segmentation tool. Studies with DPA-713-IRDye680LT and a fluorescent analog of DPA-713 as well as histopathology and flow cytometry were performed on post-mortem tissues.

Results

Infected hamsters were imaged at the peak of inflammatory lung disease (7 days post-infection). Quantitative CT analysis was successful for all scans and demonstrated worse pulmonary disease in male versus female animals (P < 0.01). Increased ¹²⁴I-iodo-DPA-713 PET activity co-localized with the pneumonic lesions. Additionally, higher pulmonary ¹²⁴I-iodo-DPA-713 PET activity was noted in male versus female hamsters (P = 0.02). DPA-713-IRDye680LT also localized to the pneumonic lesions. Flow cytometry demonstrated a higher percentage of myeloid and CD11b + cells (macrophages, phagocytes) in male versus female lung tissues (P = 0.02).

Conclusion

¹²⁴I-Iodo-DPA-713 accumulates within pneumonic lesions in a hamster model of SARS-CoV-2 infection. As a novel molecular imaging tool, ¹²⁴I-Iodo-DPA-713 PET could serve as a noninvasive, clinically translatable approach to monitor SARS-CoV-2-associated pulmonary inflammation and expedite the development of novel therapeutics for COVID-19.

SUBMITTER: Ruiz-Bedoya CA

PROVIDER: S-EPMC8381721 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Hypothyroidism is closely related to mental disorders, mainly depression, through an as-yet-unknown mechanism. The cerebral inflammatory immune process has been implied to play a pivotal role in the onset of affective symptoms in several conditions. In order to gain insight into the mechanism underlying the depressive behaviors in hypothyroid rats, brain microglial activation was evaluated using micro positron emission tomography imaging with a translocator protein (TSPO) radioligand. Hypothyroidism was induced in adult male Wistar rats by administration of 0.05% propylthiouracil in drinking water for five weeks. Open field, forced swimming and tail suspension tests were employed to evaluate the depressive behavior in hypothyroid rats, and the relationship between the behavioral changes and brain microglial activation was evaluated using [18F] DPA-714 micro positron emission tomography imaging. The open field test revealed significantly reduced first-minute activity and rearing behavior in the hypothyroid group, as well as significantly increased immobility in the forced swimming test and the tail suspension test. Hypothyroidism induced significantly increased microglial activation in the hippocampus. The radioligand uptake in the hippocampus correlated negatively with first-minute activity in the open field test (p < 0.05), and the radioligand uptake in the hippocampus correlated positively with changes in the immobility time in the forced swimming test and the tail suspension test (p < 0.05). Immunohistochemistry also confirmed the activation of microglia and inflammatory bodies in hypothyroid rats. The results indicate that hypothyroidism can induce depressive behavior in adult Wistar rats, microglial activation in the hippocampus plays an important role in the depressive behavior in hypothyroid rats and the inflammatory immune mechanism may underlie the behavioral abnormalities in thyroid dysfunction. Furthermore, the findings in the present study suggest there might be a common mechanism underlying depressive behavior in adult-onset hypothyroidism and depression.

Dataset Information

¹²⁴I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection.

Purpose

Procedures

Results

Conclusion

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection.

Purpose

Procedures

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

¹²⁴I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection.