The purpose of this study is to evaluate whether 18F-fluciclovine PET/CT of the brain, is able to distinguish radiation necrosis from tumor progression in cases where MRI is inconclusive.

18F-fluciclovine is an FDA approved radioactive diagnostic agent and is injected into the participant and then taken up by cancer cells, which can then be visualized with a PET/CT scan. 18F-fluciclovine is FDA approved for the detection of recurrent prostate cancer, but is still investigational for the purposes of this study.

The primary objective of this study is to estimate the accuracy of 18F-fluciclovine PET in distinguishing radiation necrosis from tumor progression. Accuracy will be assessed via receiver operating characteristic curve analysis, as well as by calculating sensitivity and specificity.

Secondary objectives of this study are to assess which factors may influence accuracy of 18Ffluciclovine PET in distinguishing radiation necrosis from tumor progression and to compare the accuracy of each of the qualitative and quantitative metrics.

Inclusion Criteria:

• Subjects must have a confirmed diagnosis of brain metastases.
• Subjects must have received prior intracranial SRS at least once for brain metastases. Prior WBRT is allowed.
• Subjects must have had a clinical tumor protocol MRI of the brain including a DSC-MR perfusion sequence, which is equivocal for radiation necrosis versus tumor progression within 30 days of treatment scan. "Equivocal" will be defined as being inconclusive for radiation necrosis versus tumor progression as determined by the study neuroradiologist.
• Physician assessed life expectancy of ≥ 6 months.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.
• For women of childbearing potential, a negative serum pregnancy test within 14 days of registration is required.

Exclusion Criteria:

• Subjects who have experienced a prior anaphylaxis reaction to 18Ffluciclovine are not eligible.
• Females pregnant at the expected time of 18F-fluciclovine administration are not eligible due to potential harm to the fetus from exposure to radiation. Women who could be pregnant require a negative pregnancy test to be eligible.
• Women who are breast feeding at the expected time of 18F-fluciclovine administration are not eligible due to potential harm to the infant from exposure to radiation.
• Subjects contraindicated for MRI.
• Subjects unable or unwilling to comply with study requirements are not eligible.
• Major medical illness or psychiatric impairments, which in the investigator's opinion, will prevent completion of protocol therapy and/or preclude informed consent.
• Brain metastases from primary lymphoma, germ cell tumor, or small cell carcinoma.