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

Overview

Journal Tomography

Publisher MDPI

Specialty Radiology

Date 2023 Mar 24

PMID 36961000

Authors

Seong-Woo Bae

Jianbo Wang

Dimitra K Georgiou

Xiaoxia Wen

Allison S Cohen

Ling Geng

Mohammed Noor Tantawy

H Charles Manning

Affiliations

Soon will be listed here.

Abstract

Early response assessment is critical for personalizing cancer therapy. Emerging therapeutic regimens with encouraging results in the wild-type (WT) 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-[F]fluoropropyl)-L-glutamic acid ([F]FSPG) in treatment-sensitive and treatment-resistant WT CRC patient-derived xenografts (PDXs). Tumor-bearing mice were imaged with [F]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, [F]FSPG PET was significantly decreased from baseline at 1-week post-therapy, prior to changes in tumor volume. In contrast, [F]FSPG PET was not decreased in non-responding PDX. These data suggest that [F]FSPG PET may serve as an early metric of response to EGFR and glutaminase inhibition in the WT CRC setting.

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