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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-06

AUTHORS

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

ABSTRACT

PURPOSE: [(18)F]Fluorocholine ([(18)F]FCH) was developed as an analog of [(11)C]choline for tumor imaging; however, its metabolic handling remains ill defined. In this study, the metabolism of [(18)F]FCH is evaluated in cultured 9L glioma cells and Fisher 344 rats bearing 9L glioma tumors. METHODS: 9L glioma cells were incubated with [(18)F]FCH and [(14)C]choline under normoxic and hypoxic (1% O(2)) conditions and analyzed for metabolic fate. [(18)F]FCH and [(14)C]choline kinetics and metabolism were studied in Fisher 344 rats bearing subcutaneous 9L tumors. RESULTS: [(18)F]FCH and [(14)C]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 [(18)F]phosphofluorocholine (0.043-0.060 min(-1)) and [(14)C]phosphocholine (0.072-0.088 min(-1)) was evidenced via efflux measurements. In rat, both [(18)F]FCH and [(14)C]choline showed high renal and hepatic uptake. Blood clearance of both tracers was rapid with oxidative metabolites, [(18)F]fluorobetaine and [(14)C]betaine, representing the majority of radiolabel in plasma after 5 min postinjection. Oxidation (in liver) and lipid incorporation (in lung) were somewhat slower for [(18)F]FCH relative to [(14)C]choline. The majority of radiolabel in hypoxic subcutaneous tumor, as in hypoxic cultured 9L cells, was found as nonmetabolized [(18)F]FCH and [(14)C]choline. CONCLUSIONS: [(18)F]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 [(18)F]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. More... »

PAGES

1192-1203

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00259-008-0736-y

DOI

http://dx.doi.org/10.1007/s00259-008-0736-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015841358

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18264706


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49 schema:description PURPOSE: [(18)F]Fluorocholine ([(18)F]FCH) was developed as an analog of [(11)C]choline for tumor imaging; however, its metabolic handling remains ill defined. In this study, the metabolism of [(18)F]FCH is evaluated in cultured 9L glioma cells and Fisher 344 rats bearing 9L glioma tumors. METHODS: 9L glioma cells were incubated with [(18)F]FCH and [(14)C]choline under normoxic and hypoxic (1% O(2)) conditions and analyzed for metabolic fate. [(18)F]FCH and [(14)C]choline kinetics and metabolism were studied in Fisher 344 rats bearing subcutaneous 9L tumors. RESULTS: [(18)F]FCH and [(14)C]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 [(18)F]phosphofluorocholine (0.043-0.060 min(-1)) and [(14)C]phosphocholine (0.072-0.088 min(-1)) was evidenced via efflux measurements. In rat, both [(18)F]FCH and [(14)C]choline showed high renal and hepatic uptake. Blood clearance of both tracers was rapid with oxidative metabolites, [(18)F]fluorobetaine and [(14)C]betaine, representing the majority of radiolabel in plasma after 5 min postinjection. Oxidation (in liver) and lipid incorporation (in lung) were somewhat slower for [(18)F]FCH relative to [(14)C]choline. The majority of radiolabel in hypoxic subcutaneous tumor, as in hypoxic cultured 9L cells, was found as nonmetabolized [(18)F]FCH and [(14)C]choline. CONCLUSIONS: [(18)F]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 [(18)F]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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