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
Published version of a preprint
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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“The importance of additional nutrients besides glucose to tumor metabolism has prompted the development of several new PET agents for cancer, including glutamate and glutamine (Koglin et al., 2011; Qu et al., 2011).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Koglin et al., 2011
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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
- Venue
- Clinical Cancer Research
- Published
- 2011-09-14
- Volume
- 17
- Issue
- 18
- Pages
- 6000-6011
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- 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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