Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells.
BACKGROUND
Choline, acetate and glucose ([2-(18)F]fluoro-2-deoxyglucose, [(18)F]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-(3)H]choline, [1-(14)C]acetate and [(18)F]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.


CONCLUSIONS
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.
Hara
Toshihiko
T
Department of Radiology, Indiana University School of Medicine, Indianapolis, IN 46202-9028, USA.
Bansal
Aditya
A
DeGrado
Timothy R
TR
D000085:Acetates / Q000493:pharmacokinetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D002250:Carbon Radioisotopes; D002452:Cell Count; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D002794:Choline / Q000493:pharmacokinetics*; D013196:Dihydrotestosterone / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014316:Tritium
D000085:Acetates; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D013196:Dihydrotestosterone; D019788:Fluorodeoxyglucose F18; D014316:Tritium; D000255:Adenosine Triphosphate; D002794:Choline