This study will examine whether positron emission tomography (PET) imaging with fluciclovine can reliably differentiate true progression from pseudoprogression months earlier than the conventional MRI methods.

Approximately 40-50% of all glioblastoma patients undergoing standard of care radiochemotherapy will show signs of early disease progression that includes increases in the apparent tumor size on conventional magnetic resonance imaging (MRI) scans. Unfortunately, treatment related effects, including alterations to the blood brain barrier (BBB), can mimic tumor progression on conventional MRI scans, which confounds assessment of tumor progression during and in the months following radiochemotherapy.

An imaging method that provides a reliable early assessment of brain tumor progression could enable patients to enroll into clinical trials months earlier (when tumors are more treatable) and potentially save patients from the adverse side effects of an ineffective radiochemotherapy regimen. Fluciclovine positron emission tomography (PET) imaging has the potential to overcome the limitations of conventional MRI and provide an earlier, more comprehensive assessment of brain tumor progression. Fluciclovine is a radiolabeled amino acid analogue whose transport across the BBB and retention in tumor cells is dictated primarily by upregulated amino acid transporters. Prior studies have shown that amino acid PET with radiotracers similar to fluciclovine can accurately distinguish tumor progression from treatment effects in glioma patients, but these other amino acid radiotracers are not widely available. Another advantage of fluciclovine PET is that is can detect infiltrative tumor cells that are often not discernable on standard conventional MRI and are often in regions beyond that those with disrupted BBB. There are no published studies evaluating whether fluciclovine PET can differentiate progression from treatment effects despite fluciclovine being commercially available and widely accessible. The goals of this proposal are to establish whether fluciclovine PET can: i) identify early progression at time points soon after completion of radiation therapy and ii) differentiate treatment-related effects from true disease progression in patients with suspected recurrent disease.

Inclusion Criteria:

1. Greater than 18 years of age
2. Histological diagnosis of primary WHO grade III or IV glioma
3. Completed standard radiotherapy
4. Undergoing or completed standard chemotherapy (or other therapies)
5. Enlarging or new contrast-enhancing mass suspicious for progression/recurrence (at least 10mm in one direction)
6. Subjects must agree to take adequate pregnancy preventions from the time of consent until 24 hrs after the 18F-fluciclovine injection.
7. Willing and able to provide written informed consent in compliance with the regulatory requirements. If a subject is unable to provide written informed consent, written informed consent may be obtained from the subject's legal representative

Exclusion Criteria:

1. Simultaneous participation in other interventional trials which could interfere with this trial.
2. Inability to undergo a MRI or PET scan (claustrophobia, non-MRI compatible pacemaker, renal insufficiency, known allergy to MRI contrast agent or fluciclovine tracer)
3. Subjects who are pregnant or lactating or who suspect they might be pregnant.

All participants will receive the same imaging.