Molecular imaging reveals a progressive pulmonary inflammation in lower airways in ferrets infected with 2009 H1N1 pandemic influenza virus.
Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [(18)F]-2-deoxy-2-fluoro-D-glucose ([(18)F]-FDG) as a radiotracer for PET imaging coupled with CT (FDG-PET/CT) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm). The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI). On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [(18)F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7-7.0). By days 2 and 3, consolidation (CT) and inflammation ([(18)F]-FDG) appeared in the left caudal lobe. By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO) and consolidations with the largest lesions having high SUVMax (6.0-7.6). Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively. In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [(18)F]-FDG uptake. Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman's ρ = 0.75). Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections. In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time.
Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, Kentucky, United States of America. cbjons01@louisville.edu
Colleen B
CB
Jonsson
Jeremy V
JV
Camp
Albert
A
Wu
Huaiyu
H
Zheng
Jennifer L
JL
Kraenzle
Ashley E
AE
Biller
Carol D
CD
Vanover
Yong-Kyu
YK
Chu
Chin K
CK
Ng
Mary
M
Proctor
Leslie
L
Sherwood
Marlene C
MC
Steffen
Daniel J
DJ
Mollura
D000818:Animals; D018450:Disease Progression; D005260:Female; D005289:Ferrets / Q000821:virology; D019788:Fluorodeoxyglucose F18; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D057054:Molecular Imaging; D064847:Multimodal Imaging; D009666:Nose / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000175:diagnosis* / Q000821:virology; D058873:Pandemics; D011014:Pneumonia / Q000175:diagnosis* / Q000821:virology; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed; D014779:Virus Replication; D017201:Virus Shedding
D019788:Fluorodeoxyglucose F18