Abstract
Early response assessment is critical for personalizing cancer therapy. Emerging therapeutic regimens with encouraging results in the wild-type (WT) KRAS colorectal cancer (CRC) setting include inhibitors of epidermal growth factor receptor (EGFR) and glutaminolysis. Towards predicting clinical outcome, this preclinical study evaluated non-invasive positron emission tomography (PET) with (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) in treatment-sensitive and treatment-resistant WT KRAS CRC patient-derived xenografts (PDXs). Tumor-bearing mice were imaged with [18F]FSPG PET before and one week following the initiation of treatment with either EGFR-targeted monoclonal antibody (mAb) therapy, glutaminase inhibitor therapy, or the combination. Imaging was correlated with tumor volume and histology. In PDX that responded to therapy, [18F]FSPG PET was significantly decreased from baseline at 1-week post-therapy, prior to changes in tumor volume. In contrast, [18F]FSPG PET was not decreased in non-responding PDX. These data suggest that [18F]FSPG PET may serve as an early metric of response to EGFR and glutaminase inhibition in the WT KRAS CRC setting.
Original language | English (US) |
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Pages (from-to) | 497-508 |
Number of pages | 12 |
Journal | Tomography |
Volume | 9 |
Issue number | 2 |
DOIs | |
State | Published - Apr 2023 |
Keywords
- EGFR
- FSPG
- PET
- colorectal cancer
- glutaminolysis
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
MD Anderson CCSG core facilities
- Research Animal Support Facility
- Advanced Technology Genomics Core
- Small Animal Imaging Facility