Effective Detection and Monitoring of Glioma Using [18F]FPIA PET Imaging
| Autor: | Joel Abrahams, Keittisak Suwan, Chris P. Barnes, Diana Brickute, Marta Braga, Ali Ashek, Angel M. Carcaboso, Eric O. Aboagye, Amin Hajitou, Louis Allott, Vessela Vassileva, Justyna Przystal |
|---|---|
| Přispěvatelé: | Cancer Research UK |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
proliferation Cell Medicine (miscellaneous) Pharmacology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glioma glioma medicine Transcellular Biology (General) Fatty acid metabolism Cancer Lipid metabolism medicine.disease medicine.anatomical_structure chemistry fatty acid metabolism 030220 oncology & carcinogenesis [18F]FPIA PET imaging Immunohistochemistry 030217 neurology & neurosurgery Etomoxir |
| Zdroj: | Biomedicines, Vol 9, Iss 811, p 811 (2021) Biomedicines Volume 9 Issue 7 |
| ISSN: | 2227-9059 |
| Popis: | Background: Reprogrammed cellular metabolism is a cancer hallmark. In addition to increased glycolysis, the oxidation of acetate in the citric acid cycle is another common metabolic phenotype. We have recently developed a novel fluorine-18-labelled trimethylacetate-based radiotracer, [18F]fluoro-pivalic acid ([18F]FPIA), for imaging the transcellular flux of short-chain fatty acids, and investigated whether this radiotracer can be used for the detection of glioma growth. Methods: We evaluated the potential of [18F]FPIA PET to monitor tumor growth in orthotopic patient-derived (HSJD-GBM-001) and cell line-derived (U87, LN229) glioma xenografts, and also included [18F]FDG PET for comparison. We assessed proliferation (Ki-67) and the expression of lipid metabolism and transport proteins (CPT1, SLC22A2, SLC22A5, SLC25A20) by immunohistochemistry, along with etomoxir treatment to provide insights into [18F]FPIA uptake. Results: Longitudinal PET imaging showed gradual increase in [18F]FPIA uptake in orthotopic glioma models with disease progression (p < 0.0001), and high tumor-to-brain contrast compared to [18F]FDG (p < 0.0001). [18F]FPIA uptake correlated positively with Ki-67 (p < 0.01), SLC22A5 (p < 0.001) and SLC25A20 (p = 0.001), and negatively with CPT1 (p < 0.01) and SLC22A2 (p < 0.01). Etomoxir reduced [18F]FPIA uptake, which correlated with decreased Ki-67 (p < 0.05). Conclusions: Our findings support the use of [18F]FPIA PET for the detection and longitudinal monitoring of glioma, showing a positive correlation with tumor proliferation, and suggest transcellular flux-mediated radiotracer uptake. |
| Databáze: | OpenAIRE |
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