Multiparametric Metabolic and Hypoxic PET/MRI Imaging Substudy in Gliomas

Pre-Study Consent Visit

This visit will take 0.5 hours and may take place during your neuro-oncology clinic visit or in the Division of Molecular Imaging and Therapeutics in Jefferson Tower or the Wallace Tumor Institute. Participants will be asked to sign this consent form before any study procedures. Participants will have a blood test to measure their kidney function. If participants have already had lab tests to determine kidney function within 4 weeks, they do not have to be repeated. Women of childbearing potential will have a urine pregnancy test or have had a blood test within 48 hours of consenting. If the participant is eligible, they will be scheduled to return for baseline imaging within 21 days before surgery.

Once consented, participants will fill out an MRI screening questionnaire in person or through a screening phone call. These questions will help identify and address items like claustrophobia. If participants are anxious or claustrophobic (anxious due to being in a confined area) due to the PET/MRI imaging procedures, a study physician will call in lorazepam (Ativan), 0.5 mg-1 mg based on individual patient assessment, to a pharmacy of the participants choice. One tablet is to be taken with each imaging visit as necessary. Participants will be responsible for paying for the medication and the study will not reimburse them. Participants will need to pick up the medication and bring it with them to each study visit. This medication may make participants drowsy, and they should not drive for 12 hours after taking this medication. Participants must make arrangements to have a responsible adult present to provide them with transportation home after each visit. Participants should also avoid drinking alcohol or taking opioid pain medications for at least 12 hours or use dangerous equipment after taking this medication. Additional FDA information will be given to participants during this visit describing this medication and known side effects.

Baseline Imaging (performed within 21 days of surgery)

Participants will be scheduled to have baseline imaging performed during one or two separate days based on their preference and scanner and drug production availability.

• DAY - Baseline Combo FMISO/FET-PET/MRI Imaging Visit

If participants are scheduled for baseline imaging performed during one (1) day, this visit will take about 6.5 hours. Participants will be asked to not eat or drink anything with calories for 4 hours prior to the study. When participants arrive at the Advanced Imaging Facility (AIF), located in the Wallace Tumor Institute (WTI), they will have another chance to have any questions answered about the procedure.

If participants have been prescribed lorazepam to help reduce anxiety, the study coordinator will verify they have a driver and/or transportation present. Participants will take 1 tablet by mouth upon arrival or at least one hour before the imaging procedure.

Female participants of childbearing potential will have either a blood draw or urine pregnancy test within 48 hours before administration of the radioactive drug to make sure they are not pregnant.

Before the scan, participants will have a plastic catheter inserted into a vein in each arm. Participants will be injected with [18F]FMISO and they will wait 4 hours for the drug to distribute in the body. Participants will then be positioned in the PET/MRI scanner and scanned for up to 30 minutes during which time they will receive an injection of gadolinium MR contrast agent.

Immediately following the FMISO-PET/MRI imaging, participants will receive an injection of [18F]FET and will be imaged for another 40 minutes.

Participants will be monitored during the imaging to make sure they are not experiencing any side effects and those taking lorazepam will be monitored for confusion or disorientation.

When participants have completed the PET/MRI imaging, the catheters will be removed, and they may resume normal activities.

Participants will receive a follow-up phone call within 48 hours of their imaging visit. Participants will be asked about any changes in their health and side effects that might be due to the investigational drug.

• DAY - Baseline Separate FMISO-PET/MRI and FET-PET/MRI Imaging Visits

If participants are scheduled for baseline imaging to be performed over two (2) separate days, every effort will be made to schedule these two visits within 1 week (7 days) of each other. One visit will take 2 hours and the other will take 5 hours. FET-PET/MRI will typically be performed first although the order can be switched if needed due to drug production or scanner availability.

FET-PET/MRI imaging - baseline visit (2-Day)

This visit will take about 2 hours. Participants will be asked to not eat or drink anything with calories for 4 hours prior to the study. When participants arrive at the Advanced Imaging Facility (AIF), located in the Wallace Tumor Institute (WTI), they will have another chance to have any questions answered about the procedure.

If participants have been prescribed lorazepam to help reduce anxiety, the study coordinator will verify they have a driver and/or transportation present. participants will take 1 tablet by mouth upon arrival or at least one hour before the imaging procedure.

Female participants of childbearing potential will have either a blood draw or urine pregnancy test within 48 hours before administration of the radioactive drug to make sure they are not pregnant.

Before the scan, participants will have a plastic catheter inserted into a vein in one or both arm(s) and positioned in the PET/MRI. Participants will be injected with [18F]FET and imaged for up to 40 minutes during which time they will receive an injection of gadolinium MR contrast agent.

Participants will be monitored during the imaging to make sure they are not experiencing any side effects and those taking lorazepam will be monitored for confusion or disorientation.

When participants have completed the PET/MRI imaging, the catheters will be removed, and they may resume normal activities.

Participants will receive a follow-up phone call within 48 hours of their imaging visit. Participants will be asked about any changes in their health and side effects that might be due to the investigational drug.

FMISO-PET/MRI imaging - baseline visit (2-Day)

This visit will take up to 5 hours. No fasting or other special preparation is required for this visit. When participants arrive at the Advanced Imaging Facility (AIF), located in the Wallace Tumor Institute (WTI), they will have another chance to have any questions answered about the procedure.

If participants have been prescribed lorazepam to help reduce anxiety, the study coordinator will verify they have a driver and/or transportation present. participants will take 1 tablet by mouth upon arrival or at least one hour before the imaging procedure.

Female participants of childbearing potential will have either a blood draw or urine pregnancy test within 48 hours before administration of the radioactive drug to make sure they are not pregnant.

Before the scan, participants will have a plastic catheter inserted into a vein in one or both arms. Participants will be injected with [18F]FMISO and they will wait 4 hours for the drug to distribute in the body. Participants will then be positioned in the PET/MRI scanner and scanned for up to 30 minutes during which time they will receive an injection of gadolinium MR contrast agent.

Participants will be monitored during the imaging to make sure they are not experiencing any side effects and those taking lorazepam will be monitored for confusion or disorientation.

When participants have completed the PET/MRI imaging, the catheters will be removed, and they may resume normal activities.

Participants will receive a follow-up phone call within 48 hours of their imaging visit. Participants will be asked about any changes in their health and side effects that might be due to the investigational drug.

Post Surgery Follow up FET-PET/MRI visits

After the participant's surgery as directed under the main study (IRB 300007756), they will be scheduled for follow-up FET-PET/MRI imaging at approximately 1 month, 3 months and 6-8 months.

Each of these visits will take about 2 hours. Participants will be asked to not eat or drink anything with calories for 4 hours prior to each imaging visit.

If participants have been prescribed lorazepam to help reduce anxiety, the study coordinator will verify they have a driver and/or transportation present. participants will take 1 tablet by mouth upon arrival or at least one hour before the imaging procedure.

Female participants of childbearing potential will have either a blood draw or urine pregnancy test within 48 hours before administration of the radioactive drug to make sure they are not pregnant.

Before the scan, participants will have a plastic catheter inserted into a vein in one or both arm(s) and positioned in the PET/MRI. Participants will be injected with [18F]FET and imaged for up to 40 minutes during which time they will receive an injection of gadolinium MR contrast agent.

Participants will be monitored during the imaging to make sure they are not experiencing any side effects and those taking lorazepam will be monitored for confusion or disorientation.

When participants have completed the PET/MRI imaging, the catheters will be removed, and they may resume normal activities.

Participants will receive a follow-up phone call within 48 hours of their imaging visit. Participants will be asked about any changes in their health and side effects that might be due to the investigational drug.

If the PET/MRI is unexpectedly unavailable during any of the imaging visits, participants may undergo brain PET imaging on a scanner located in an adjacent room to the PET/MRI. The radioactive drug administration and PET imaging will be identical to the protocol described above for PET/MRI but participants will not receive MRI contrast.

Clinical follow up

The study team will continue to follow participant's health through their regular clinic visits and imaging as directed under the main study (IRB 300007756).

Inclusion criteria

• Participants from IRB 300007756
• 18 years of age or older at the time of enrollment
• Able to undergo PET/MRI without anesthesia or sedation. Minimal sedation with ananxiolytic such as alprazolam used routinely for SOC MRI is allowed.
• Females with childbearing potential must have a negative urine β-hCG test on the day of procedure or a serum hCG test within 48 hours prior to the administration of FET or FMISO.
• ECOG performance score of 2 or better
• Life expectancy greater than 12 weeks.

Exclusion criteria

• Any exclusions listed in IRB 300007756
• Pregnancy or breast feeding
• Inability to complete PET/MRI scans.
• Significant renal dysfunction (estimated GFR < 30 mL/min)
• Any condition which may interfere with ability to participate in or complete all study-related activities as assessed by the study team
• Unable to undergo MRI
• Contraindication to gadolinium-based contrast