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Effective detection and monitoring of glioma using [18F]FPIA PET imaging

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Title: Effective detection and monitoring of glioma using [18F]FPIA PET imaging
Authors: Vassileva, V
Braga, M
Barnes, C
Przystal, J
Ashek, A
Allott, L
Brickute, D
Abrahams, J
Suwan, K
Carcaboso, AM
Hajitou, A
Aboagye, EO
Item Type: Journal Article
Abstract: 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.
Issue Date: 13-Jul-2021
Date of Acceptance: 9-Jul-2021
URI: http://hdl.handle.net/10044/1/90403
DOI: 10.3390/biomedicines9070811
ISSN: 2227-9059
Publisher: MDPI
Start Page: 1
End Page: 14
Journal / Book Title: Biomedicines
Volume: 9
Issue: 7
Copyright Statement: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: 16584
Publication Status: Published
Online Publication Date: 2021-07-13
Appears in Collections:Department of Surgery and Cancer

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