Radiolabeling and Preclinical Evaluation of [77Br]hGTS13, an xCT-Targeted Small Molecule
- 1Stanford University , , , ,
Abstract
System xc– is an amino acid antiporter overexpressed in numerous cancers, including glioma, pancreatic, and lung cancers. Different glutamate derivative radiotracers allow for the imaging of system xc– by positron emission tomography (PET), such as [18F]hGTS13. Our goal was to radiolabel hGTS13 with the therapeutic Auger electron emitter bromine-77 (77Br) and determine if system xc– tolerates the substitution of fluorine-18 (18F) by 77Br. [77Br]hGTS13 was radiosynthesized by a nucleophilic aliphatic radiobromination. Its uptake in the nonsmall cell lung cancer cell lines H460 and A549 showed a high and sustained uptake. A competition assay with the natural substrates of system xc– and a synthetic inhibitor proved the specificity of [77Br]hGTS13. It remained 100% intact in human serum after a 1 h incubation at 37 °C. Ex vivo biodistribution studies in H460 tumor-bearing nude mice and rats showed similar tumor-associated radioactivity for [18F]hGTS13 and [77Br]hGTS13, but [77Br]hGTS13 was not stable, and the tumor uptake must therefore be interpreted with caution. The in vitro results prove that system xc– tolerates the substitution of the imaging radioisotope by a therapeutic one; however, in vivo stability requires careful consideration.
Related
- Drug–Drug Conjugates as Intelligent Preclinical Platforms for Targeted Cancer Therapy
- Radiolabeling with fluorine-18 of a protein, interleukin-1 receptor antagonist
- Olive Oil as a Potential Source of Anticancer Phytochemicals: In Vitro and Preclinical Evaluation of Active Ingredients and Their Synergism with Conventional Treatments
- MassSpecGym in the Wild: Uncovering and Correcting Evaluation Pitfalls in AI-Driven Molecule Discovery
- A Dual Mechanism-Based Physiologically Based Pharmacokinetic Model for Predicting Mitoxantrone and Liposomal Mitoxantrone Disposition: Preclinical Validation in Rats and Human Extrapolation with Clinical Evaluation.
BibTeX
@article{malek2026radiolabeling,
title = {{Radiolabeling and Preclinical Evaluation of [77Br]hGTS13, an xCT-Targeted Small Molecule}},
author = {Rim Malek and Pierre Cheung and Abraham Moses and Madeleine Landry and Corinne Beinat},
journal = {ACS Omega},
year = {2026},
month = nov,
doi = {10.1021/acsomega.6c05073},
url = {https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c05073/5461931/Radiolabeling-and-Preclinical-Evaluation-of-77Br},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Radiolabeling and Preclinical Evaluation of [77Br]hGTS13, an xCT-Targeted Small Molecule
AU - Rim Malek
AU - Pierre Cheung
AU - Abraham Moses
AU - Madeleine Landry
AU - Corinne Beinat
PY - 2026
DA - 2026/11/01
JO - ACS Omega
DO - 10.1021/acsomega.6c05073
UR - https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c05073/5461931/Radiolabeling-and-Preclinical-Evaluation-of-77Br
AB - System xc– is an amino acid antiporter overexpressed in numerous cancers, including glioma, pancreatic, and lung cancers. Different glutamate derivative radiotracers allow for the imaging of system xc– by positron emission tomography (PET), such as [18F]hGTS13. Our goal was to radiolabel hGTS13 with the therapeutic Auger electron emitter bromine-77 (77Br) and determine if system xc– tolerates the substitution of fluorine-18 (18F) by 77Br. [77Br]hGTS13 was radiosynthesized by a nucleophilic aliphatic radiobromination. Its uptake in the nonsmall cell lung cancer cell lines H460 and A549 showed a high and sustained uptake. A competition assay with the natural substrates of system xc– and a synthetic inhibitor proved the specificity of [77Br]hGTS13. It remained 100% intact in human serum after a 1 h incubation at 37 °C. Ex vivo biodistribution studies in H460 tumor-bearing nude mice and rats showed similar tumor-associated radioactivity for [18F]hGTS13 and [77Br]hGTS13, but [77Br]hGTS13 was not stable, and the tumor uptake must therefore be interpreted with caution. The in vitro results prove that system xc– tolerates the substitution of the imaging radioisotope by a therapeutic one; however, in vivo stability requires careful consideration.
SN - 2470-1343
ER -