Description

Objectives

1. Evaluate the kinetics of dynamic brain FES PET/CT and optimize acquisition protocol.
2. Evaluate utility of FES PET/CT as an adjunct modality in radiotherapy planning.
3. (Exploratory aim) Determine correlation between FES PET metrics and survival metrics.

Overall Design All subjects will undergo a MRI brain and FDG PET/CT brain scan as part of clinical standard- of-care for radiation treatment planning. An additional 18F-FES PET/CT brain scan will be performed as part of this study prior to standard of care radiation treatment. 18F-FES is clinically approved for the study population, however has to date not been widely used in the clinical context of differentiating brain metastases from radiation sequela. The 18F-FES PET/CT scan will be completed within approximately 2 days to 4 weeks of the 18F-FDG PET/CT, and 2 days to 4 weeks of the MRI brain, respectively. While MRI and PET can be performed on the same day if needed, the 18F-FDG PET/CT and 18F-FES PET/CT have to be separated by at least 1 day, to allow for 10 half-lives of 18F (10 times 108 minutes = 18 hours) to pass in order to avoid signal overlap on the second PET/CT scan. Subjects will be followed prospectively with clinical and MRI assessments per clinical standard-of-care for a total of 12 months.

Aim 1

• 5 mCi FES +/- 10% will be injected intravenously (per manufacturer's recommendations). FES PET/CT will be obtained in dynamic 3D list mode for 90 minutes starting from injection.
• Kinetic analysis of dynamic PET images will be carried out using a reversible 1-tissue-2- compartment model as well as Logan Vt, and the influx rate constant, Ki, and distribution volume, Vt, will measured respectively.
• Static 10min PET images will be generated for from 50 to 80 min on a 10min increment, and the corresponding SUV's and tumor-to-background ratios will be compared to that in the 80- 90min imageset, a workflow that previously established by our group using DOTATATE PET/MR in meningioma, and using FLT/FMISO PET/CT in high-grade glioma.
• Tumor volume will be delineated using PMOD (PMOD, Zurich), a dedicated tool for PET analyses and kinetic modeling.

Aim 2.

• To evaluate utility of FES PET/CT in RT planning, planning treatment volumes will be delineated by a radiation oncologist in conjunction with a neurosurgeon based on MRI (gold standard); subsequently, the FES PET/CT data will be made available to the radiation oncologist, and the planning treatment volume (PTV) will be modified accordingly if necessary.
• The clinical treatment plan will be modified (as a proof-of-concept) based on the MRI+FES PTV, and the target dose volume histograms (DVH) will be compared to the MRI-based (gold standard).
• Change in management based on additional information provided in the PET data will be recorded. In an exploratory analysis, FES PET will be compared with standard of care FDG PET/CT or PET/MR for treatment planning.