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

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. KleinSanjay K. Jain

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	135-143
Number of pages	9
Journal	Molecular Imaging and Biology
Volume	24
Issue number	1
DOIs	https://doi.org/10.1007/s11307-021-01638-5
State	Published - Feb 2022

Keywords

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

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1007/s11307-021-01638-5

Cite this

Ruiz-Bedoya, C. A., Mota, F., Ordonez, A. A., Foss, C. A., Singh, A. K., Praharaj, M., Mahmud, F. J., Ghayoor, A., Flavahan, K., De Jesus, P., Bahr, M., Dhakal, S., Zhou, R., Solis, C. V., Mulka, K. R., Bishai, W. R., Pekosz, A., Mankowski, J. L., Villano, J., ... Jain, S. K. (2022). ¹²⁴I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection. Molecular Imaging and Biology, 24(1), 135-143. https://doi.org/10.1007/s11307-021-01638-5

Ruiz-Bedoya, CA, Mota, F, Ordonez, AA, Foss, CA, Singh, AK, Praharaj, M, Mahmud, FJ, Ghayoor, A, Flavahan, K, De Jesus, P, Bahr, M, Dhakal, S, Zhou, R, Solis, CV, Mulka, KR, Bishai, WR , Pekosz, A , Mankowski, JL , Villano, J , Klein, SL & Jain, SK 2022, '¹²⁴I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection', Molecular Imaging and Biology, vol. 24, no. 1, pp. 135-143. https://doi.org/10.1007/s11307-021-01638-5

@article{36bf21ed965d41bfb55b3279d373b4fc,

title = "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.",

keywords = "COVID-19, Immune response, Macrophage, Molecular imaging, PET/CT, SARS-CoV-2, Sex difference",

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

note = "Publisher Copyright: {\textcopyright} 2021, World Molecular Imaging Society.",

year = "2022",

month = feb,

doi = "10.1007/s11307-021-01638-5",

language = "English (US)",

volume = "24",

pages = "135--143",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer New York",

number = "1",

}

TY - JOUR

T1 - 124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection

AU - Ruiz-Bedoya, Camilo A.

AU - Mota, Filipa

AU - Ordonez, Alvaro A.

AU - Foss, Catherine A.

AU - Singh, Alok K.

AU - Praharaj, Monali

AU - Mahmud, Farina J.

AU - Ghayoor, Ali

AU - Flavahan, Kelly

AU - De Jesus, Patricia

AU - Bahr, Melissa

AU - Dhakal, Santosh

AU - Zhou, Ruifeng

AU - Solis, Clarisse V.

AU - Mulka, Kathleen R.

AU - Bishai, William R.

AU - Pekosz, Andrew

AU - Mankowski, Joseph L.

AU - Villano, Jason

AU - Klein, Sabra L.

AU - Jain, Sanjay K.

PY - 2022/2

Y1 - 2022/2

N2 - 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.

AB - 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.

KW - COVID-19

KW - Immune response

KW - Macrophage

KW - Molecular imaging

KW - PET/CT

KW - SARS-CoV-2

KW - Sex difference

UR - http://www.scopus.com/inward/record.url?scp=85113777710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85113777710&partnerID=8YFLogxK

U2 - 10.1007/s11307-021-01638-5

DO - 10.1007/s11307-021-01638-5

M3 - Article

C2 - 34424479

AN - SCOPUS:85113777710

SN - 1536-1632

VL - 24

SP - 135

EP - 143

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 1

ER -