(124)I-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.

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 (124)I-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 (124)I-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 (124)I-iodo-DPA-713 PET activity co-localized with the pneumonic lesions. Additionally, higher pulmonary (124)I-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: (124)I-Iodo-DPA-713 accumulates within pneumonic lesions in a hamster model of SARS-CoV-2 infection. As a novel molecular imaging tool, (124)I-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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11307-021-01638-5.