imaging of apoptosis in chronic obstructive pulmonary disease (copd)

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Summary: this will be a prospective study examining the use of 99mtc-annexin v-128 (axv-128/tc) single-photon emission computed tomography (spect)/computerized tomography (ct) technology in the imaging and functional assessment of the lung of patients with chronic obstructive pulmonary disease (copd), healthy volunteer smokers without copd and healthy volunteer subjects without smoking history. the aim of study is to determine if patients with copd have an increased axv-128/tc signal with spect/ct.

chronic obstructive pulmonary disease (copd) is the third leading cause of death and is characterized by clinical symptoms and spirometry. additional measures for diagnosis can be taken using imaging modalities such as ct. however, the evaluation of lung destruction in copd is limited by the inability to visualize the activation of pathological processes since imaging modalities are only able to evaluate end-organ damage. in this proposal, the investigators aim to assess a molecular imaging probe targeting apoptosis, a cellular process known to be pathogenic in copd. apoptosis, a process of programmed cellular death, correlates with copd severity and is not seen in the normal adult lung. in the past several years the investigators have demonstrated the successful ability of axv-128/tc to detect apoptosis in vivo in a preclinical animal model of smoke exposure emphysema model. additionally, phase 1 studies have demonstrated safety of this agent in healthy patients. therefore, the investigators will bring axv-128/tc forward as a probe to image the apoptotic disease process of the lung in patients with copd. the investigators will determine if the imaging signal correlates with serum biomarkers of apoptosis and inflammation. it is the investigators' hypothesis that axv-128/99mtc imaging will show increased uptake in the lungs of patients with copd, and that this signal intensity will correlate with accepted markers of apoptosis and inflammation. if successful, such an approach will be a powerful tool to potentially predict disease progression after diagnosis, identify patients at risk for disease exacerbation related lung function decline, and monitor response to disease targeted therapy. the total effective dose from the combined spect and ct scans is 6.2 millisievert (msv). this effective dose is below what a patient receives during a standard 2 dose rest and stress cardiac nuclear imaging study and well within the range of current clinical nuclear imaging tests. the exact long term risk for development of cancer from diagnostic radiological procedures is currently under debate but all imaging procedures in this study are aimed to keep total radiation burden as low as reasonably achievable (alara).

Eligibility criteria:
inclusion criteria: * patients with moderate copd: global initiative for chronic obstructive lung disease (gold) stage ii, forced expiratory volume 1 (fev1)/forced vital capacity (fvc) \< 0.7 and fev1 50-79% predicted * patients with severe copd: gold stage iii-iv, fev1/fvc \< 0.7 and fev1 \< 50% predicted * healthy controls who are currently smoking (\> 10 pack years) with normal spirometry (fev1 \> 80% and fev1/fvc \> 70%) * healthy controls who never smoked (less than 100 lifetime cigarettes) with normal spirometry (fev1 \> 80% and fev1/fvc \> 70%) exclusion criteria: * age \< 18 years

Keywords: chronic obstructive pulmonary disease (copd)