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

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

Comments

Trial registration: ClinicalTrials.gov NCT 03263429.

Supplementary Materials

Data Availability Statement

PMID: 36961000