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A7608 - Detection of Apoptosis in Smokers Using Functional Molecular Imaging
Author Block: M. P. Goldklang1, L. Fonseca1, R. Yeh2, G. Wagener1, L. L. Johnson3, J. M. D'Armiento1; 1Anesthesiology, Columbia University, New York, NY, United States, 2Radiology, Columbia University, New York, NY, United States, 3Medicine, Columbia University, New York, NY, United States.
INTRODUCTION: Molecular imaging targeting cellular processes related to disease pathogenesis has the potential to assess disease activity over time to allow for clinical intervention prior to lung destruction. Apoptosis is elevated in the lungs of patients who are active smokers. We have recently demonstrated the efficacy of apoptosis targeted Annexin V-128 SPECT-CT imaging in the rabbit smoke exposure model of emphysema. Therefore, a molecular imaging approach was undertaken to determine if there is a detectable apoptotic signal in the lungs of current smokers to allow the quantification of early lung damage in vivo. METHODS: Current smokers without known lung disease and lifelong non-smokers were recruited. After consent and complete pulmonary function testing, a peripheral IV was placed and 10 mCi 99mTc rhAnnexin-128 (AxV-128/Tc) was injected. Patients were imaged 2.5-3 hours later on a Siemen’s Symbia SPECT/CT scanner. Regions of interest on 10 pixel thick transverse sections around each lung were drawn using CT for anatomical location and counts for each slice converted to mCi, then summed for all slices. Lung activity was divided by decay corrected injected dose and multiplied by 100 to yield % injected dose. RESULTS: Over five months, three life-long non-smokers and five active smokers without COPD were recruited. There was no difference between current smokers and lifelong non-smokers with regards to FEV1, FEV1% predicted, FEV1/FVC, DLCO, and DLCO% predicted. Specifically, in control subjects as compared to current smokers, FEV1 was 2.83±0.43 L and 2.83±0.72 L, FEV1% predicted was 86.3±19.2% and 84.8±6.3%, and FEV1/FVC 78.3±2.1% and 72.2±5.1%, respectively. DLCO was 23.7±3.9 ml/min/mmHg in control and 21.7±5.9 ml/min/mmHg in current smokers; DLCO% predicted was 75.3±5.5% in control and 69±10.4% in current smokers. Radiotracer blood pool clearance was established between 2-3 hours in healthy control patients. Imaging analysis revealed a trend towards an increase in %ID of AxV-128/Tc in smokers, with uptake in the right lung 0.22±0.02% in control and 0.28±0.02% in current smokers and uptake in the left lung 0.16%±0.03% and 0.19%±0.03% respectively. No adverse events occurred in imaged patients. CONCLUSIONS: This proof-of-concept study demonstrates that AxV-128/Tc SPECT-CT imaging is feasible in a patient population. With limited enrollment, there is a trend towards increased AxV-128/Tc uptake in current smokers without obstructive lung disease. These studies characterize a promising imaging modality that can identify ongoing destructive cellular processes within the lung of patients. Future studies in patients with emphysema will determine the clinical utility of this technology.