The prospective single-arm pilot study, ATHERO-RT: Real-Time Atherosclerosis Activity after Thoracic Radiotherapy using Sodium Fluoride Positron Emission Tomography, will aim to:

1. To deploy first-in-kind application of fluorine 18-sodium fluoride (18F-NaF) PET (Positron Emission Tomography) /MRI (Magnetic Resonance Imaging) imaging to detect real-time atherosclerosis activity at the time of cancer diagnosis and after cardiac radiation exposure
2. To detect longitudinal changes in clonal hematopoiesis (CH) genetic architecture following thoracic RT (Radiation Therapy) in patients at high risk of cardiac dysfunction, and
3. To measure perturbations in the immune-modulatory and metabolic states following thoracic RT (Radiation Therapy) exposure in patients at high risk of cardiac dysfunction.

Eligible patients will be adults (≥18 years old) with Stage II-III or oligo-metastatic stage IV malignancy (any histology) at high risk for RT-associated cardiac toxicity (defined as receiving ≥30 Gy (Gray) RT where the heart is in the treatment field54). The study will enroll a total of 10 subjects, recruited from Cedars-Sinai Medical Center. The primary endpoint will be successful completion of 18F-NaF PET imaging at the baseline and 6-month post-RT time points. Blood will be collected at baseline, end of RT, and 6-months post-RT.

Inclusion Criteria

• Age ≥ 18 years.
• Have clinical stage II-III or oligo-metastatic stage IV malignancy (any histology) planned to be treated with thoracic radiotherapy (≥30 Gy) where the heart is in the treatment field.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
• Planning to receive standard of care radiotherapy treatment.
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
• Ability to read, write, and understand English

Exclusion Criteria

• Estimated glomerular filtration rate (eGFR) <45 mL/min/m2 or serum creatinine ≥1.5 mg/dL.
• Patients with a known or previous allergy to iodinated contrast, gadolinium contrast, and/or 18F-NaF tracer.
• Inability to receive PET tracer.
• Inability to receive MRI, requiring sedation for MRI, or prohibitive implant and/or device, including ferromagnetic implants and ferromagnetic foreign bodies.
• Subjects with claustrophobia, problems being in enclosed spaces, or inability to lie supine.
• Subjects that are pregnant or breastfeeding.
• Subjects unable to comply with visit instructions, including inability to lie still, hold breathe, or follow procedure instructions.
• Allergy to animal dander or animal-instigated asthma.
• Any other condition which, in the opinion of the investigator, may make the patient a poor candidate for participation in a clinical trial