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

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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1192-1203
Number of pages12
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume35
Issue number6
DOIs
StatePublished - Jun 2008

Fingerprint

Glioma
Choline
Neoplasms
fluorocholine
Betaine
Phosphorylcholine
Liver
Lipid Metabolism
Positron-Emission Tomography
Radioactivity
Cultured Cells
Phosphorylation
Kidney
Lipids
Lung

Keywords

  • 9L glioma
  • F
  • Choline
  • Fluorocholine
  • Hypoxia
  • Metabolism
  • Rat

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Biodisposition and metabolism of [18F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats. / Bansal, Aditya; Shuyan, Wang; Hara, Toshiko; Harris, Robert; DeGrado, Timothy R.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 35, No. 6, 06.2008, p. 1192-1203.

Research output: Contribution to journalArticle

@article{e9edbb3432614581bebc552f7f8c2692,
title = "Biodisposition and metabolism of [18F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats",
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.",
keywords = "9L glioma, F, Choline, Fluorocholine, Hypoxia, Metabolism, Rat",
author = "Aditya Bansal and Wang Shuyan and Toshiko Hara and Robert Harris and DeGrado, {Timothy R.}",
year = "2008",
month = "6",
doi = "10.1007/s00259-008-0736-y",
language = "English",
volume = "35",
pages = "1192--1203",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
issn = "1619-7070",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Biodisposition and metabolism of [18F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats

AU - Bansal, Aditya

AU - Shuyan, Wang

AU - Hara, Toshiko

AU - Harris, Robert

AU - DeGrado, Timothy R.

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

KW - 9L glioma

KW - F

KW - Choline

KW - Fluorocholine

KW - Hypoxia

KW - Metabolism

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=43749106842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43749106842&partnerID=8YFLogxK

U2 - 10.1007/s00259-008-0736-y

DO - 10.1007/s00259-008-0736-y

M3 - Article

VL - 35

SP - 1192

EP - 1203

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

SN - 1619-7070

IS - 6

ER -