Intraoperative Imaging of Pulmonary Nodules by OTL38

According to the World Health Organization, lung cancer is the most common cause of
cancer-related death in men and women, and is responsible for 1.5 million deaths worldwide
annually as of 2012. Surgery remains the best option for patients presenting with operable
Stage I or II cancers, however the five year survival rate for these candidates remains at a
dismal 73% for Stage I and 53% for Stage II. The high rates of local recurrence suggest that
surgeons are unable to completely detect and remove primary tumor nodules in a satisfactory
manner as well as lingering metastases in sentinel lymph nodes. By ensuring a negative margin
through imaging during surgery it would be possible for the investigators to improve the
rates of recurrence free patients and thus overall survival.

Thoracic malignancies are the ideal disease to investigate intra-operative imaging. Over 85%
of lung and pleural malignancies express folate receptor alpha (FRA), therefore making folate
receptors (FR) the ideal targets for imaging agents. While folate will initially distribute
to all cells, redistribution, metabolism, and excretion will eliminate most of this agent
from healthy tissues within hours. Tumor cells that over express FRα will retain folate and
any fluorescent labeled folate conjugate and internalize this. It is important to note that
FRA is expressed only in the proximal tubules of the kidneys, activated macrophages, and in
the choroidal plexus. However, the fluorescence signal in the kidneys is expected to be
significantly lower than the tumor tissues. Thus, the false positive detection rate is
expected to be extremely low.

The investigators have conducted a Phase I clinical trial with folate-FITC in 50 patients
with lung cancer. In the study at UPenn, the investigators had no adverse events. The
investigators had excellent sensitivity and specificity with this technique with only grade 1
side effects (allergic reaction). All side effects reversed when the injection was halted.
This study confirmed that FRA is a reasonable target for lung cancer.

On Target Laboratories, LLC has developed OTL38. Compared with some of the existing
fluorescent imaging agents, OTL38 is associated with less auto-fluorescence due to its
near-IR excitation wavelength and can be seen through blood and tissues up to 1.5 cm
thickness. Thus, in this study, the investigator's goal has changed from the folate-FITC
formulation to the OTL38 formulation. The fluorophore component of the drug is new, whereas
the target and design of the study remain unchanged.

Inclusion Criteria:

- Adult patients over 18 years of age

- Patients presenting with a lung or pleural nodule or mass presumed to be resectable on
pre- operative assessment

- Good operative candidate

- Subject capable of giving informed consent and participating in the process of
consent.

Exclusion Criteria:

- Pregnant women as determined by urinary or serum beta hCG within 72 hours of surgery

- Patients with a history of anaphylactic reactions to OTL38

- Patients with a known allergy to Benadryl

- At-risk patient populations:

- Homeless patients

- Patients with drug or alcohol dependence

- Children and neonates

- Patients unable to participate in the consent process.