The objective of this research project is to investigate anfr-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-[ F]FACBC) to image gliomas based upon amino acid transport with the imaging technique Positron Emission Tomography (PET). Our approach will focus on anti-[18F]FACBC, a non-metabolized amino acid (AA) that moves across tumor capillaries involving primarily the "L" large-neutral AA transport system (LAT). Preliminary evaluation of AAs labeled with positron emitters and which are substrates for the LAT has shown excellent potential for tumor imaging in patients with gliomas. The development of LAT radiotracers with optimal imaging properties remains an active area of investigation. Our choice of anti-[18F]FACBC as a suitable radiotracer for imaging tumors stems from our in vitro studies in human U87 glioma cells demonstrating that anti-[18F]FACBC shows high and selective uptake by the LAT and our in vivo studies with anf/-[18F]FACBC in humans with primary gliomas (n=11) and metastatic brain tumors (n=15) displayed high 6:1 tumor to brain ratios support our proposed studies to evaluate anti-[18F]FACBC in humans in order to determine its potential as an imaging agent for gliomas.
The Specific Aims of this proposal are: 1) Perform anti-[18F]FACBC and [18F]FDG PET to measure anti-[18F]FACBC transport rate and [18F]FDG metabolism, respectively in low and high grade gliomas during the course of the patient's treatment: a) After tumor needle biopsy;b) After the initial cycle of radiation therapy;c) When MR imaging indicates tumor progression;2) Perform anti-[18F]FACBC and [18F]FDG PET to measure anti-[18F]FACBC transport rate and [18F]FDG metabolism just prior to tumor biopsy or resection to address tumor recurrence or radiation necrosis;3) Perform co-registration of anti-[18F]FACBC and [18F]FDG PET with MRI in low and high grade gliomas to compare measurement of tumor distribution and volume;4) Perform anti-[18F]FACBC and [18F]FDG PET in patients with MRI nonenhancing tumors to assess whether anti-[18F]FACBC can distinguish low grade tumors from malignant ones more accurately than [18F]FDG;5) Compare AA transporter character from tumor specimens with histology and anf/-[18F]FACBC imaging and kinetics to determine if LAT expression is a good predictor of tumor control and survival;and 6) Perform anti-[18F]FACBC scans to measure AA transport rate in low grade gliomas prior to the patient's treatment: a) After tumor needle biopsy;and b) at 7 days to determine test re-test variability. Our hypothesis is that FACBC is superior to FDG for neuro tumor imaging applications We expect the following improvements: 1) more accurate histologic grading in humans than [18F]FDG;2) LAT expression is upregulated in brain tumors in proportion to the growth rate, transport rate and tumor grade;3) anti-[18F]FACBC transport rate in tumor measured prior to and following therapy will correlate to survival;4) anti-[18F]FACBC tumor uptake will provide a more accurate correlation of the extent of the viable tumor distribution compared to MRI or with [18F]FDG and 5) anti-[18F]FACBC tumor uptake will provide a more accurate distinction between radiation necrosis and viable tumor than MRI) and [18F]FDG).