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European Journal of Nuclear Medicine and Molecular Imaging

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01-06-2008 | Original Article

Biodisposition and metabolism of [¹⁸F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats

Authors: Aditya Bansal, Wang Shuyan, Toshiko Hara, Robert A. Harris, Timothy R. DeGrado

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2008

Abstract

Purpose

[¹⁸F]Fluorocholine ([¹⁸F]FCH) was developed as an analog of [¹¹C]choline for tumor imaging; however, its metabolic handling remains ill defined. In this study, the metabolism of [¹⁸F]FCH is evaluated in cultured 9L glioma cells and Fisher 344 rats bearing 9L glioma tumors.

Methods

9L glioma cells were incubated with [¹⁸F]FCH and [¹⁴C]choline under normoxic and hypoxic (1% O₂) conditions and analyzed for metabolic fate. [¹⁸F]FCH and [¹⁴C]choline kinetics and metabolism were studied in Fisher 344 rats bearing subcutaneous 9L tumors.

Results

[¹⁸F]FCH and [¹⁴C]choline were similarly metabolized in 9L cells in both normoxic and hypoxic conditions over a 2-h incubation period. In normoxia, radioactivity was predominantly in phosphorylated form for both tracers after 5-min incubation. In hypoxia, the tracers remained mainly in nonmetabolized form at early timepoints (<20 min). Slow dephosphorylation of intracellular [¹⁸F]phosphofluorocholine (0.043–0.060 min⁻¹) and [¹⁴C]phosphocholine (0.072–0.088 min⁻¹) was evidenced via efflux measurements. In rat, both [¹⁸F]FCH and [¹⁴C]choline showed high renal and hepatic uptake. Blood clearance of both tracers was rapid with oxidative metabolites, [¹⁸F]fluorobetaine and [¹⁴C]betaine, representing the majority of radiolabel in plasma after 5 min postinjection. Oxidation (in liver) and lipid incorporation (in lung) were somewhat slower for [¹⁸F]FCH relative to [¹⁴C]choline. The majority of radiolabel in hypoxic subcutaneous tumor, as in hypoxic cultured 9L cells, was found as nonmetabolized [¹⁸F]FCH and [¹⁴C]choline.

Conclusions

[¹⁸F]FCH mimics choline uptake and metabolism by 9L glioma cells and tumors. However, subtle changes in biodistribution, oxidative metabolism, dephosphorylation, lipid incorporation, and renal excretion show moderate effects of the presence of the radiofluorine atom in [¹⁸F]FCH. The decrease in phosphorylation of exogenous choline by cancer cells should be considered in interpretation of positron emission tomography images in characteristically hypoxic tumors.

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Title: Biodisposition and metabolism of [18F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats
Authors: Aditya Bansal
Wang Shuyan
Toshiko Hara
Robert A. Harris
Timothy R. DeGrado
Publication date: 01-06-2008
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-008-0736-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Biodisposition and metabolism of [¹⁸F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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