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This study is designed to apply various scans such as functional imaging, Fluorodeoxyglucose_Positron Emission Tomography (FDG-PET), 62Cu-ETS (Copper) PET, Ventilation/Perfusion Single Photon Emission Computerized Tomography (V/Q SPECT), cardiac magnetic resonance imaging (MRI), Tc-99m HMPAO SPECT/CT, and pulmonary function tests before, during and after treatment to see if it predicts how well the treatment works for your cancer and how well your lungs function during treatment. A Computerized Tomography (CT) will also be performed along with both of these procedures to help the researchers see clearly where your cancer or your healthy lung is located. The researchers also perform blood tests in this study to look for markers in your blood to see if it helps them determine your risk of developing side effects from radiation to the lungs. They will also measure your health-related quality of life before, during and after treatment. The researchers hope that this study will help them in the future to design radiation treatment plans that provide the best treatment for each individual patient.

Primary aims:

1. To determine if tumor metabolic activity plus volume measured by 18F-FDG PET/CT and tissue/tumor perfusion measured by 62Cu-ETS-PET before and during treatment predicts CT tumor response 3 months after completion of treatment and 1 and 2 year local-regional progression-free survival.
2. To determine if functional imaging based lung dose-volume histograms (DVH) more accurately predict changes in diffusion capacity of lung for carbon monoxide (DLCO) compared to the DVH based on simulating CT. Degree of lung toxicity will also be documented by functional scans such as Tc-99m HMPAO imaging.
3. To determine if baseline level, or changes in blood markers such as TGFß1 measured during the course of radiation, predict changes in DLCO.

Potentially eligible patients include all patients with stage I to IV lung cancer. Patient cannot have started systemic treatments or radiation treatments prior to enrollment on the study. Informed consent will be obtained in writing prior to initiating the study using a consent form approved by the local IRB.

Inclusion criteria

• Histologically confirmed lung cancer, or clinically diagnosed lung cancer.
• AJCC stage I to IV lung cancer requiring radiation therapy (3D conformal or stereotactic) or systemic therapy, with or without surgery.
• Patients participating treatment trials including targeted therapy, experimental therapy or immunotherapy are also eligible.
• Patients with a locoregional tumor recurrence following surgery will be eligible provided they meet other eligibility criteria.
• Patients must be 18 years of age or older and able to lie flat to obtain the functional scans or have blood access for blood samples
• Female patients with reproductive capability must be willing to use effective contraception.
• Patients must be willing and able to be compliant with all procedures and visits required for this protocol (pre-treatment, during treatment, and optionally throughout follow-up period).
• Patients must sign an informed consent form for study.
• Patients must be willing and able to adhere to a special low-carb diet 24-48 hours prior to and fast 8-12 hours prior to every 18F-FDG PET scan

Exclusion criteria

• Pregnancy if the patient is receiving radiation therapy
• Lactation if the patient is receiving radiation therapy
• Patients with diabetes mellitus, with uncontrolled fasting blood glucose level (above 200 mg/dl)
• Inability to lie flat for the duration of PET/CT and V/Q SPECT/CT (approximately 45 minutes for each study)

Lung cancer patients