[18F]FDG functional PET revisited: A new perspective on the temporal dynamics of brain glucose metabolism
- 1Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- 2Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
- 3Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
Abstract
[18F]FDG functional PET (fPET) enables investigation of dynamics in glucose metabolism occurring within seconds. However, the physiological mechanisms supporting rapid metabolic changes necessitate further attention to allow accurate interpretation. This work highlights candidate mechanisms driving [18F]FDG signal changes at high temporal resolution, offering complementary insights to existing interpretations. At rest, metabolic demands are closely matched by glucose supply across the blood-brain barrier (BBB), regulated by glucose transporter 1 (GLUT1). During neuronal activation, glucose transport and phosphorylation by hexokinase are elevated to meet increased energy requirements. Simulations indicate that rapid [18F]FDG signal increases are primarily driven by BBB transport, with subsequent increases in hexokinase activity. Mechanisms supporting increased BBB transport include elevated glucose concentration gradient towards the brain and changes in GLUT1 intrinsic properties, but only minor effects of blood flow. Conversely, moment-to-moment fluctuations in [18F]FDG used for metabolic connectivity, reflect temporally synchronized supply, mediated jointly by blood flow and BBB transport. We emphasize that the coupling between BBB transport and metabolism underpin the [18F]FDG fPET signal. Considering alterations of GLUT1 and subsequent metabolism in numerous brain disorders, stimulation-induced energy demands and metabolic connectivity represent a promising opportunity to investigate the underlying pathophysiological processes.
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BibTeX
@article{hahn202618ffdg,
title = {{[18F]FDG functional PET revisited: A new perspective on the temporal dynamics of brain glucose metabolism}},
author = {Andreas Hahn and Pia Falb and Matej Murgaš and Sebastian Klug and Murray B Reed and Godber M Godbersen and Magdalena Ponce de León and Christian Milz and Marcus Hacker and Dan Rujescu and Rupert Lanzenberger},
journal = {Journal of Cerebral Blood Flow \& Metabolism},
year = {2026},
month = jun,
doi = {10.1177/0271678x261455750},
url = {https://doi.org/10.1177/0271678x261455750},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - [18F]FDG functional PET revisited: A new perspective on the temporal dynamics of brain glucose metabolism
AU - Andreas Hahn
AU - Pia Falb
AU - Matej Murgaš
AU - Sebastian Klug
AU - Murray B Reed
AU - Godber M Godbersen
AU - Magdalena Ponce de León
AU - Christian Milz
AU - Marcus Hacker
AU - Dan Rujescu
AU - Rupert Lanzenberger
PY - 2026
DA - 2026/06/01
JO - Journal of Cerebral Blood Flow & Metabolism
DO - 10.1177/0271678x261455750
UR - https://doi.org/10.1177/0271678x261455750
AB - [18F]FDG functional PET (fPET) enables investigation of dynamics in glucose metabolism occurring within seconds. However, the physiological mechanisms supporting rapid metabolic changes necessitate further attention to allow accurate interpretation. This work highlights candidate mechanisms driving [18F]FDG signal changes at high temporal resolution, offering complementary insights to existing interpretations. At rest, metabolic demands are closely matched by glucose supply across the blood-brain barrier (BBB), regulated by glucose transporter 1 (GLUT1). During neuronal activation, glucose transport and phosphorylation by hexokinase are elevated to meet increased energy requirements. Simulations indicate that rapid [18F]FDG signal increases are primarily driven by BBB transport, with subsequent increases in hexokinase activity. Mechanisms supporting increased BBB transport include elevated glucose concentration gradient towards the brain and changes in GLUT1 intrinsic properties, but only minor effects of blood flow. Conversely, moment-to-moment fluctuations in [18F]FDG used for metabolic connectivity, reflect temporally synchronized supply, mediated jointly by blood flow and BBB transport. We emphasize that the coupling between BBB transport and metabolism underpin the [18F]FDG fPET signal. Considering alterations of GLUT1 and subsequent metabolism in numerous brain disorders, stimulation-induced energy demands and metabolic connectivity represent a promising opportunity to investigate the underlying pathophysiological processes.
SN - 0271-678X
SN - 1559-7016
ER -