Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells

Toshihiko Hara, Aditya Bansal, Timothy R DeGrado

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Introduction: Choline, acetate and glucose ([2-18F]fluoro-2-deoxyglucose, [18F]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified. Methods: The uptake of [methyl-3H]choline, [1-14C]acetate and [18F]FDG was monitored in androgen-independent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined. Results: PC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85% increase in FDG uptake, a 15% decrease in choline uptake and a 36% increase in acetate uptake, whereas LNCaP cells showed a 212% increase in FDG uptake, a 28% decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells. Conclusion: In aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline>acetate>FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy.

Original languageEnglish (US)
Pages (from-to)977-984
Number of pages8
JournalNuclear Medicine and Biology
Volume33
Issue number8
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Fluorodeoxyglucose F18
Choline
Prostatic Neoplasms
Acetates
Androgens
Positron-Emission Tomography
Hypoxia
Androgen Antagonists
Glucose

Keywords

  • Acetate
  • Choline
  • FDG
  • Hypoxia
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells. / Hara, Toshihiko; Bansal, Aditya; DeGrado, Timothy R.

In: Nuclear Medicine and Biology, Vol. 33, No. 8, 11.2006, p. 977-984.

Research output: Contribution to journalArticle

@article{d335347eec884baca842ea16c1430a50,
title = "Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells",
abstract = "Introduction: Choline, acetate and glucose ([2-18F]fluoro-2-deoxyglucose, [18F]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified. Methods: The uptake of [methyl-3H]choline, [1-14C]acetate and [18F]FDG was monitored in androgen-independent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined. Results: PC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85{\%} increase in FDG uptake, a 15{\%} decrease in choline uptake and a 36{\%} increase in acetate uptake, whereas LNCaP cells showed a 212{\%} increase in FDG uptake, a 28{\%} decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells. Conclusion: In aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline>acetate>FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy.",
keywords = "Acetate, Choline, FDG, Hypoxia, Prostate cancer",
author = "Toshihiko Hara and Aditya Bansal and DeGrado, {Timothy R}",
year = "2006",
month = "11",
doi = "10.1016/j.nucmedbio.2006.08.002",
language = "English (US)",
volume = "33",
pages = "977--984",
journal = "International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells

AU - Hara, Toshihiko

AU - Bansal, Aditya

AU - DeGrado, Timothy R

PY - 2006/11

Y1 - 2006/11

N2 - Introduction: Choline, acetate and glucose ([2-18F]fluoro-2-deoxyglucose, [18F]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified. Methods: The uptake of [methyl-3H]choline, [1-14C]acetate and [18F]FDG was monitored in androgen-independent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined. Results: PC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85% increase in FDG uptake, a 15% decrease in choline uptake and a 36% increase in acetate uptake, whereas LNCaP cells showed a 212% increase in FDG uptake, a 28% decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells. Conclusion: In aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline>acetate>FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy.

AB - Introduction: Choline, acetate and glucose ([2-18F]fluoro-2-deoxyglucose, [18F]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified. Methods: The uptake of [methyl-3H]choline, [1-14C]acetate and [18F]FDG was monitored in androgen-independent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined. Results: PC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85% increase in FDG uptake, a 15% decrease in choline uptake and a 36% increase in acetate uptake, whereas LNCaP cells showed a 212% increase in FDG uptake, a 28% decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells. Conclusion: In aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline>acetate>FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy.

KW - Acetate

KW - Choline

KW - FDG

KW - Hypoxia

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=33751246442&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751246442&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2006.08.002

DO - 10.1016/j.nucmedbio.2006.08.002

M3 - Article

VL - 33

SP - 977

EP - 984

JO - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology

JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology

SN - 0969-8051

IS - 8

ER -