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124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection.
Ruiz-Bedoya, Camilo A; Mota, Filipa; Ordonez, Alvaro A; Foss, Catherine A; Singh, Alok K; Praharaj, Monali; Mahmud, Farina J; Ghayoor, Ali; Flavahan, Kelly; De Jesus, Patricia; Bahr, Melissa; Dhakal, Santosh; Zhou, Ruifeng; Solis, Clarisse V; Mulka, Kathleen R; Bishai, William R; Pekosz, Andrew; Mankowski, Joseph L; Villano, Jason; Klein, Sabra L; Jain, Sanjay K.
Affiliation
  • Ruiz-Bedoya CA; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mota F; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
  • Ordonez AA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Foss CA; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Singh AK; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
  • Praharaj M; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mahmud FJ; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ghayoor A; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
  • Flavahan K; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • De Jesus P; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Bahr M; Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Dhakal S; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zhou R; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Solis CV; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mulka KR; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
  • Bishai WR; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Pekosz A; Invicro, Boston, MA, USA.
  • Mankowski JL; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Villano J; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
  • Klein SL; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Jain SK; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mol Imaging Biol ; 24(1): 135-143, 2022 02.
Article in En | MEDLINE | ID: mdl-34424479
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.
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Full text: 1 Database: MEDLINE Main subject: Pyrazoles / Pyrimidines / Positron-Emission Tomography / SARS-CoV-2 / COVID-19 / Iodine Radioisotopes / Acetamides Limits: Animals Language: En Year: 2022 Type: Article
Fulltext
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PubMed Links
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Full text: 1 Database: MEDLINE Main subject: Pyrazoles / Pyrimidines / Positron-Emission Tomography / SARS-CoV-2 / COVID-19 / Iodine Radioisotopes / Acetamides Limits: Animals Language: En Year: 2022 Type: Article