Imaging of Apoptosis in Chronic Obstructive Pulmonary Disease (COPD)

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).

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