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Cited by 120Radiopharmaceutical Chemistry and ApplicationsMedical Imaging Techniques and ApplicationsCancer, Hypoxia, and Metabolism

The DOI matches its Crossref record; 45 of the 51 references it cites were found in a registry or an index.

Specific PET imaging of xC- transporter activity using a 18F-labeled glutamate derivative reveals a dominant pathway in tumor metabolism

Koglin, Norman, Mueller, Andre, Berndt, Mathias, Schmitt-Willich, Heribert, Toschi, Luisella, Stephens, Andrew W., Gekeler, Volker, Friebe, Matthias, Dinkelborg, Ludger M.·2011·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-11-0687

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Abstract

PURPOSE: (18)F-labeled small molecules targeting adaptations of tumor metabolism possess the potential for early tumor detection with high sensitivity and specificity by positron emission tomography (PET) imaging. Compounds tracing deranged pathways other than glycolysis may have advantages in situations where 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) has limitations. The aim of this study was the generation of a metabolically stable ¹⁸F-labeled glutamate analogue for PET imaging of tumors. EXPERIMENTAL DESIGN: Derivatives of l-glutamate were investigated in cell competition assays to characterize the responsible transporter. An automated radiosynthesis was established for the most promising candidate. The resulting ¹⁸F-labeled PET tracer was characterized in a panel of in vitro and in vivo tumor models. Tumor specificity was investigated in the turpentine oil-induced inflammation model in rats. RESULTS: A fluoropropyl substituted glutamate derivative showed strong inhibition in cell uptake assays. The radiosynthesis was established for (4S)-4-(3-[¹⁸F]fluoropropyl)-l-glutamate (BAY 94-9392). Tracer uptake studies and analysis of knockdown cells showed specific transport of BAY 94-9392 via the cystine/glutamate exchanger designated as system x(C)(-). No metabolites were observed in mouse blood and tumor cells. PET imaging with excellent tumor visualization and high tumor to background ratios was achieved in preclinical tumor models. In addition, BAY 94-9392 did not accumulate in inflammatory lesions in contrast to FDG. CONCLUSIONS: BAY 94-9392 is a new tumor-specific PET tracer which could be useful to examine system x(C)(-) activity in vivo as a possible hallmark of tumor oxidative stress. Both preclinical and clinical studies are in progress for further characterization.

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Research works printed but not linked: 2

  1. Krause, 2010, [18F]BAY 85-8050 (TIM-1): a novel tumor specific probe for PET/CT imaging - First clinical results, J Nucl Med, 51, 118
  2. Vander, 2010, Evidence for an alternative glycolytic pathway in rapidly proliferating cells, Science, 329, 1492, 10.1126/science.1188015 · DOI

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Metadata

Authors
Koglin, N., Mueller, A., Berndt, M., Schmitt-Willich, H., Toschi, L., Stephens, A. W., Gekeler, V., Friebe, M., & Dinkelborg, L. M.
Affiliations
  • Bayer (Germany) (DE)
  • Authors' Affiliation: Global Drug Discovery, Bayer HealthCare, Berlin, Germany
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2011-09-14
Volume
17
Issue
18
Pages
6000-6011
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-11-0687
OpenAlex
W2142880945
Cited by
120
References
51
Citations by year
2026: 5 · 2025: 4 · 2024: 3 · 2023: 8 · 2022: 8 · 2021: 7 · 2020: 14 · 2019: 9 · 2018: 9 · 2017: 8 · 2016: 9 · 2015: 11 · 2014: 9 · 2013: 8 · 2012: 8
FWCI
6.11
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
Bayer HealthCare
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
system xc-, cystine/glutamate exchanger, cancer metabolism, radiotracer synthesis, tumor-specific imaging, tumor-to-background ratio
MeSH terms
Animals, Female, Glutamates, Humans, Mice, Nude, Neoplasms, Rats, Nude, Tomography, X-Ray Computed, Signal Transduction, Radiopharmaceuticals, Xenograft Model Antitumor Assays, Amino Acid Transport System y+, Cell Line, Tumor, Positron-Emission Tomography, Mice, Rats, Multimodal Imaging

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