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Nuklearmedizin 2021; 60(02): 90-98
DOI: 10.1055/a-1308-0589
Original Article

Characterization of activation induced [18]F-FDG uptake in Dendritic Cells

Charakterisierung der aktivierungsinduzierten [18]F-FDG-Aufnahme in dendritische Zellen
Stefanie Pektor
1   Department of Nuclear Medicine, University Medical Center Mainz, Germany
,
Laura Lawaczeck
1   Department of Nuclear Medicine, University Medical Center Mainz, Germany
,
Stephan Tenzer
2   Institute for Immunology, University Medical Center Mainz, Germany
,
Nicole Bausbacher
1   Department of Nuclear Medicine, University Medical Center Mainz, Germany
,
Manuela Andrea Hoffmann
1   Department of Nuclear Medicine, University Medical Center Mainz, Germany
3   Federal Ministry of Defense, Department of Occupational Health & Safety, Bonn, Germany
,
Mathias Schreckenberger
1   Department of Nuclear Medicine, University Medical Center Mainz, Germany
,
Matthias Miederer
1   Department of Nuclear Medicine, University Medical Center Mainz, Germany
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Abstract

Aim Activation of immune cells leads to enhanced glucose uptake that can be visualized by [18]F-Fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT). Dendritic cells (DC) are essential for the function of the adaptive immune system. In contrast to other immune cells metabolic changes leading to an increase of [18]F-FDG uptake are poorly investigated. Here, we analysed the impact of different DC activation pathways on their [18]F-FDG uptake. This effect was then used to radiolabel DC with [18]F-FDG and track their migration in vivo.

Methods DC were generated from bone marrow progenitors (BMDC) or isolated from spleens (SPDC) of C57BL/6 mice. After stimulation with the TLR ligands LPS and CpG or anti-CD40 antibody for up to 72 hours activation markers and glucose transporters (GLUTs) were measured by flow cytometry. Uptake of [18]F-FDG was measured by gamma-counting. DC lysates were analysed for expression of glycolysis relevant proteins by mass spectrometry (MS). [18]F-FDG-labeled DC were injected into footpads of mice to image DC migration.

Results BMDC and SPDC showed strong upregulation of activation markers predominantly 24 hours after TLR stimulation followed by higher uptake of [18]F-FDG. In line with this, the expression of GLUTs was upregulated during the course of activation. Furthermore, MS analyses of DC lysates revealed differential regulation of glycolysis relevant proteins according to the stimulatory pathway. As a proof of principle, DC were labeled with [18]F-FDG upon activation to follow their migration in vivo via PET/MRI.

Conclusion Immune stimulation of DC leads to enhanced [18]F-FDG uptake into DC, representing the typical shift to aerobic glycolysis in immune cells after activation.

Zusammenfassung

Ziel Aktivierung von Immunzellen führt zu einer erhöhten Zuckeraufnahme, die durch [18]F-FDG-PET/CT dargestellt werden kann. Dendritische Zellen (DC) sind essentiell für die Funktion des adaptiven Immunsystems. Im Gegensatz zu anderen Immunzellen sind metabolische Veränderungen, die zu einer Erhöhung der [18]F-FDG Aufnahme führen nur wenig untersucht. In dieser Studie wurde der Einfluss verschiedener DC-Aktivierungswege auf ihre [18]F-FDG Aufnahme untersucht. Dieser Effekt wurde dann genutzt, um DC mit [18]F-FDG zu markieren und ihre Migration in vivo zu verfolgen.

Methoden DC wurden entweder aus Knochenmarksvorläufern generiert (BMDC) oder aus Milzen von C57BL/6 Mäusen isoliert (SPDC). NAch Stimulation mit den TLR Liganden LPS und CpG oder anti-CD40 Antikörper über 72 Stunden wurden Aktivierungsmarker und Glukosetransporter (GLUTs) durchflusszytometrisch analysiert. Die [18]F-FDG Aufnahme wurde im Gamma-Counter gemessen. DC Lysate wurden auf Expression Glykolyse-relevanter Proteine mittels MAssenspektrometrie (MS) untersucht. [18]F-FDG markierte DC wurden in die Fußsohle von Mäusen injiziert, um deren Migration in vivo bildgebend darzustellen.

Ergebnisse BMDC und SPDC zeigten vor allem 24 Stunden nach TLR Stimulation eine starke Aufregulation von Aktivierungsmarkern, gefolgt von einer erhöhten [18]F-FDG Aufnahme. Gleichzeitig war auch die GLUT Expression hochreguliert. Die MS-Analyse der DC-Lysate zeigte eine differentielle Regulation von Glykolyse-relevanten Proteinen, die mit dem Stimulationsweg einherging. Als Proof of Principle wurden aktivierte DC mit [18]F-FDG markiert, um ihre Migration in vivo mittels PET/MR zu verfolgen.

Schlussfolgerung Immunstimulation dendritischer Zellen führt zu einer erhöhten [18]F-FDG Aufnahme, was den typischen Shift zur aeroben Glykolyse in aktivierten Immunzellen wiederspiegelt.

Key words

dendritic cells - [18]F-FDG uptake - metabolism - glucose transporter - immune system

Schlüsselwörter

dendritische Zellen - [18]F-FDG Aufnahme - Metabolismus - Glukosetransporter - Immunsystem

Supplement



Publication History

Received: 09 September 2020

Accepted: 09 November 2020

Article published online:
16 December 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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