Patient recruitment
Potential participants will be identified through the UAB and Children's of Alabama (CoA)
Neuro-Oncology, Neurosurgery and Radiation Oncology services. Patients seen in UAB
clinics and/or discussed in multi-disciplinary neuro-oncology tumor board meetings may be
approached to participate in this study. Potential participants can be enrolled from the
time that the plan for standard of care therapy is selected through the time of the first
standard of care of MRI after radiation therapy. Given that high grade gliomas are much
more frequent in adults than children, we expect to recruit mostly adults in this study.
Confirmation of patient eligibility
The following information will be collected to confirm patient eligibility prior to the
administration of FET.
Registering physician's name.
Participant's sex, race and date of birth.
Copy of signed consent form
Completed eligibility checklist that has been signed and dated by a member of the
study team.
Copy of source documentation confirming patient eligibility.
Initial Visit
Potential participants will meet with study personnel in the appropriate neuro-oncology
clinic or on the 7th floor of Jefferson Tower/Quarterback Tower. For pediatric patients
under the age of consent, a parent or legal guardian will provide consent, and when
possible and age appropriate, the child will provide assent. Questions will be answered,
and once the participant signs informed consent, blood will be drawn to measure serum
creatinine and calculate estimated GFR (eGFR). In pediatric patients, this blood draw
will also be used to measure cystatin C for use in eGFR calculation. Serum creatinine and
cystatin C measurements will not be required if results from previous tests within the
past 4 weeks are available and meet eligibility requirements. For women with childbearing
potential, a serum beta-hCG pregnancy test will be drawn along with the serum creatinine
blood draw; a urine pregnancy test is acceptable to avoid a blood draw if no serum
creatinine measurement is needed.
PET/MRI visits
After confirmation of patient eligibility and consent, the administration of FET and
FMISO and related procedures will be performed in the UAB Advanced Imaging Facility (AIF)
at the time of first SOC MRI after completion of RT (typically a 4-week interval). FET
and FMISO PET/MRI studies will be performed on separate days within 2 weeks of each
other, and every effort will be made to perform these studies within 1 week of each
other. FET-PET/MRI will typically be performed before FMISO-PET/MRI although the order
can be switched if needed from due to PET tracer production or scanner scheduling.
Patients will fast for at least 4 hours prior to FET administration. No fasting or other
special preparation is required for FMISO studies. Upon arrival in the AIF, the patient
(and their legal medical decision maker if needed) will have an opportunity to have any
remaining questions answered regarding the procedure.
The participant will have a plastic peripheral intravenous (IV) catheter placed in the
arm for PET tracer and MR contrast administration. FET and FMISO will be produced by the
UAB Cyclotron PET Production Facility. PET/MRI will be performed using a GE Signa PET/MRI
system in the AIF with specific imaging protocols for FET and FMISO studies. Upon
completion of imaging, the peripheral IV catheter will be removed. The participant will
be asked to urinate to reduce bladder dose after completion of each PET acquisition. The
PET data will be reconstructed using OSEM algorithms with correction for radionuclide
decay, randoms and scatter according to the manufacturer's standard procedure.
Attenuation correction will be performed using standard MR-based attenuation correction
according to the manufacturer's recommendations.
If the PET/MRI is unexpectedly unavailable, participants can undergo brain PET imaging on
a GE 710 PET/CT scanner located adjacent to the PET/MRI scanner in the AIF. The PET
tracer administration and PET acquisition will be identical to the protocol described
previously for PET/MRI. Attenuation correction of the PET data will be based on a low
dose head CT (120 kVp, 30 mAs) for the PET/CT study. Participants undergoing PET/CT will
have a separately acquired MRI study using the same MRI sequences described previously
for the PET/MRI study.
FET-PET/MRI protocol
The patient will be positioned in the PET/MRI scanner prior to FET administration. FET (5
mCi, 185 MBq) will be administered IV as a bolus with dynamic acquisition of brain
PET/MRI data from the time of injection through 60 min after injection. The dynamic
FET-PET data will be framed according to the following schedule: 12 x 5 sec, 12 x 10 sec,
6 x 20 sec, 15 x 60 sec, and 5 min for the remainder of the study. The raw PET data will
be retained for possible future reprocessing.
During FET-PET acquisition, brain MRI will be acquired simultaneously. Multiplanar,
multisequence contrast-enhanced MR images will be acquired based on the standard of care
adult brain tumor imaging protocol at UAB and will include dynamic contrast enhanced
(DCE) and diffusion weighted (DW) sequences as well as a 3D post-contrast T1 sequence to
calculate contrast enhancing volumes and 3D FLAIR sequence to calculate non-enhancing
peritumoral volumes.
FMISO-PET/MRI protocol
The patient will undergo IV administration of FMISO (5 mCi, 185 MBq) in an uptake room in
the AIF. At approximately 4 hours after injection, the patient will be positioned on the
PET/MRI scanner. A PET scan will be acquired for 30 min, and simultaneous
contrast-enhanced MRI will be acquired which may include repeat DCE and DW sequences.
Participant Follow-up
The patients and/or their legally authorized representative will be asked about any
adverse events at the conclusion of each PET scan. They will also be contacted by
telephone 24-48 hours after PET tracer administration to confirm that the participant is
in their usual state of health and to assess for any adverse events related to the
imaging study. No additional follow up to assess for adverse events will be performed
unless a possible study-related adverse event is reported.
Duration of Follow Up:
Patients enrolled in the study will be followed clinically and with standard of care
brain MRI. PFS and OS will be monitored for up to 24 months after completion of FET and
FMISO PET/MRI studies. Relevant medical information may be accessed by study team members
for correlation with imaging results including clinic notes, diagnostic imaging,
histopathology and genetic tumor markers relevant to HGG classification and prognosis
(e.g. MGMT promotor methylation, IDH mutation status). Study participants will not
undergo additional study related procedures after completion of the FET-PET/MRI and
FMISO-PET/MRI studies.