Student and Faculty Publications
Publication Date
2-24-2023
Journal
Tomography
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.
Keywords
Humans, Mice, Animals, Glutaminase, Glutamine, Proto-Oncogene Proteins p21(ras), Glutamates, Feasibility Studies, Positron-Emission Tomography, ErbB Receptors, Disease Models, Animal, Colorectal Neoplasms
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
Comments
Trial registration: ClinicalTrials.gov NCT 03263429.
Supplementary Materials
Data Availability Statement
PMID: 36961000