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

Camilo A Ruiz-Bedoya; Filipa Mota; Alvaro A Ordonez; Catherine A Foss; Alok K Singh; Monali Praharaj; Farina J Mahmud; Ali Ghayoor; Kelly Flavahan; Patricia De Jesus; Melissa Bahr; Santosh Dhakal; Ruifeng Zhou; Clarisse V Solis; Kathleen R Mulka; William R Bishai; Andrew Pekosz; Joseph L Mankowski; Jason Villano; Sabra L Klein; Sanjay K Jain

doi:10.1007/s11307-021-01638-5

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

Mol Imaging Biol. 2022 Feb;24(1):135-143. doi: 10.1007/s11307-021-01638-5. Epub 2021 Aug 23.

Authors

Camilo A Ruiz-Bedoya^#^{1

2

3}, Filipa Mota^#^{1

2

3}, Alvaro A Ordonez^{1

2

3}, Catherine A Foss^{1

4}, Alok K Singh³, Monali Praharaj⁵, Farina J Mahmud^{1

2

3}, Ali Ghayoor⁶, Kelly Flavahan^{1

2

3}, Patricia De Jesus^{1

2

3}, Melissa Bahr^{1

2

3}, Santosh Dhakal⁷, Ruifeng Zhou⁷, Clarisse V Solis⁸, Kathleen R Mulka⁸, William R Bishai³, Andrew Pekosz^{7

8}, Joseph L Mankowski⁸, Jason Villano⁸, Sabra L Klein^#⁷, Sanjay K Jain^{9

10

11

12}

Affiliations

¹ Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
³ Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Invicro, Boston, MA, USA.
⁷ W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁸ Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA. sjain5@jhu.edu.
¹⁰ Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA. sjain5@jhu.edu.
¹¹ Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA. sjain5@jhu.edu.
¹² Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. sjain5@jhu.edu.

^# Contributed equally.

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.

Keywords: COVID-19; Immune response; Macrophage; Molecular imaging; PET/CT; SARS-CoV-2; Sex difference.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acetamides / chemistry*
Animals
COVID-19 / diagnostic imaging*
COVID-19 / veterinary*
Chlorocebus aethiops
Cricetinae
Disease Models, Animal
Iodine Radioisotopes / chemistry*
Lung / diagnostic imaging
Lung / pathology
Lung / virology
Positron Emission Tomography Computed Tomography
Positron-Emission Tomography*
Pyrazoles / chemistry*
Pyrimidines / chemistry*
SARS-CoV-2 / physiology*
Vero Cells

Substances

Acetamides
Iodine Radioisotopes
Iodine-124
N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide
Pyrazoles
Pyrimidines

Abstract

Publication types

MeSH terms

Substances

Grants and funding