Subjects with histologically proven glioblastoma (GBM) who are suspected to have progression and are candidates for a surgical resection according to standard of care may be eligible for this study. Subjects may participate in this study if they are at least 18 years of age.

Positron emission tomography (PET/CT) imaging will be used to evaluate fluciclovine uptake at sites of suspected progression before planned surgery. In addition, clinical brain MRI with and without contrast will be used to evaluate the tumor pre-operatively. This is a non-therapeutic trial in that imaging will not be used to direct treatment decisions.

Investigators anticipate enrolling up to 30 subjects who will undergo a clinical brain MRI examination with and without contrast and a research 18F-Fluciclovine PET/CT scan of the brain prior to surgery. They will also have a blood draw preoperatively to collect samples for cfDNA analysis. PET/CT imaging sessions will include an injection of approximately 5 mCi (range for most studies is anticipated to be 5 mCi +/- 20%) of 18F-Fluciclovine.

This is a pilot study in subjects with a histologically proven diagnosis of glioblastoma (GB) who have completed chemoradiation and now have new contrast enhancing lesions or lesions showing increased enhancement ( 25% increase) who are recommended for a clinical surgical resection. Subjects may participate in this study if they are at least 18 years of age, most participants will be receiving care at the clinical practices of the University of Pennsylvania. Subjects who come to the University of Pennsylvania for diagnosis and/or treatment of GB and who meet the study inclusion criteria may be approached by study personnel for recruitment into this study. Subjects will be approached about study participation regardless of race or ethnic background. Investigators anticipate enrolling up to 30 participants. Subjects who consent but do not complete the study imaging will be considered not evaluable and will be replaced. Accrual will likely occur over approximately 1-2 years. After undergoing screening assessments and verifying eligibility for study participation subjects will undergo a research 18FFluciclovine PET/CT scan of the brain and a clinical brain MRI with and without gadolinium contrast, all baseline imaging will be done prior to (within 1 week) of the surgical procedure. The PET-CT and MRI can be performed in any order.

Inclusion Criteria:

1. Participants will be ≥ 18 years of age
2. Initial diagnosis of glioblastoma (histologic or molecular proof)
3. Completion of chemoradiation
4. New contrast-enhancing lesion or lesions showing increased enhancement (>25% increase) on standard MRI after completion of chemoradiation
5. Recommended for clinically surgical resection
6. Life expectancy of greater than 3 months in the opinion of an investigator or treating physician.
7. Karnofsky performance status ≥ 60
8. Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures

Exclusion Criteria:

1. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
2. Females who are pregnant or breast feeding at the time of screening will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening.
3. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
4. Contraindications to MRI or use of gadolinium contrast