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Feasibility of [18F]FSPG PET for Early Response Assessment to Combined Blockade of EGFR and Glutamine Metabolism in Wild-Type KRAS Colorectal Cancer

Authors :
Seong-Woo Bae
Jianbo Wang
Dimitra K. Georgiou
Xiaoxia Wen
Allison S. Cohen
Ling Geng
Mohammed Noor Tantawy
H. Charles Manning
Source :
Tomography, Vol 9, Iss 2, Pp 497-508 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

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.

Details

Language :
English
ISSN :
2379139X and 23791381
Volume :
9
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Tomography
Publication Type :
Academic Journal
Accession number :
edsdoj.7bba86abc15c4a00878842bb77ff7c15
Document Type :
article
Full Text :
https://doi.org/10.3390/tomography9020041