Herein, we show for the first time the feasibility of utilizing [ 18 F]-FDG PET coupled with CT imaging of H1N1pdm in ferret to track the progression of pulmonary disease in real-time. We chose a low passage clinical isolate, KY/180, which has a change in the HA1 gene, D222G. The D222G change in H1N1pdm correlates with increased severity of disease in patient cases from several countries [37] [38] [39] [40] . The patient from which we obtained the KY/180 isolate also had a severe course of influenza illness over a period of 19 days that resulted in death. Recently, studies in mice and ferrets infected with pandemic influenza viruses A/California/04/2009 and A/Netherlands/602/2009 engineered with the D222G mutation have shown that the D222G mutation are lethal in mice, but not ferret [41, 42] . The lethality in mice, but not ferrets, has been attributed to the greater abundance of a2-3-SA in the mouse model [42, 43] . All of these viruses have an affinity for a2,6-SAs associated with attachment to and replication in cells of the upper respiratory tract as shown by the high levels of viral replication in the nasal turbinates. Thus, infection of ferrets with these H1N1pdm isolates engineered with D222G and our clinical isolate have not correlated with clinical findings in patients. These results in ferrets are not surprising given that 80% of the fatal cases of H1N1pdm had underlying medical conditions and bacterial infections [6] . Discovery of the molecular components of the host response that may promote pathogenesis will be critical for defining new treatments.