Feasibility Study Using Imaging Biomarkers in Lung Cancer

The recent report of the findings of the National Lung Screening Trial indicates that
screening a high-risk population using low dose CT results in a 20% reduction in lung cancer
mortality. At our institution, some of positive nodules that are 1 cm or larger would be
imaged using combined fluoro-deoxyglucose positron emission tomography (FDG PET)/CT. Highly
suspicious nodules would be biopsied if the risks were manageable. Otherwise, the suspicious
nodules not eligible for biopsy and so-called "indeterminate" nodules are followed using CT
to be evaluated for interval growth.

The overall goal of this project is to assess several very promising imaging biomarkers that
can reflect either the physiological or metabolic status of these nodules in order to develop
more accurate imaging algorithms for follow-up that are either less invasive or do not use
ionizing radiation or both. Based on our experience with other cancers and our preliminary
results in lung cancer, we have identified four potential imaging studies that we believe
have the potential to result in validated "imaging biomarkers" that can either individually,
or in combination, characterize malignancies. Since tumors tend to exhibit angiogenesis and
altered vascular permeability, we and others, have found that analyses of dynamic contrast
enhanced MRI (DCEMRI) can be employed as "imaging biomarkers" for malignancy. Tumors often
exhibit higher cellularity than benign or normal tissue suggesting that pixel-by-pixel ADC
values derived from diffusion weighted MRI could be useful imaging biomarkers. Finally,
measuring alterations in metabolic fluxes through the use of pathway specific C-13 labeled
compounds, a technique pioneered here at the Advanced Imaging Research Center (AIRC) at UT
Southwestern, has shown the capability of providing metabolic fingerprints for malignant and
benign tissue. This approach, while invasive, could identify and validate markers that can be
detected non-invasively in future studies. We will also employ advanced metabolomics methods
to identify potential signature "onco-metabolites" in these lung cancers.

Inclusion Criteria:

- Subjects of all races and ethnic origins over 18 years of age will be recruited.

- Patients must have suspicious or known to be malignant solitary pulmonary nodule,5cm
or less in size.

Exclusion Criteria:

- Patients with a contraindication to MRI examinations will be excluded from this study.

Contraindications to MRI examinations include:

- Medically unstable

- Heart failure

- Unstable angina

- Child bearing

- Lactating

- Not a surgical candidate

- Any contraindication per MRI Screening Form (Appendix A attached). This is the same
form used in clinical practice at UT Southwestern.

- Titanium implants, pacemakers

- Poorly controlled diabetes

- Body weight greater than 300 pounds

- Claustrophobic

- Since each patient is receiving a gadolinium based contrast agent intravenously:

- eGFR < 45 mL/min/1.73m2

- Sickle cell disease

- Hemolytic anemia