Late Imaging with [1-(11)C]Acetate Improves Detection of Tumor Fatty Acid Synthesis with PET.
Tumors are often characterized by high levels of de novo fatty acid synthesis. The kinetics of acetate incorporation into tricarboxylic acid cycle intermediates and into lipids suggest that detection of tumors with [1-(11)C]acetate PET could be improved by imaging at later time points.


METHODS
The uptake and metabolism of [1-(11)C], [1-(13)C], and [1-(14)C]acetate were measured in mouse prostate and lung cancer models to investigate the time course of (11)C label incorporation into tumor metabolites.


RESULTS
Radioactivity in the lipid fraction, as compared with the aqueous fraction, in extracts of C4-2B human prostate xenografts peaked at 90 min after [1-(14)C]acetate injection, which coincided with peak (13)C label incorporation into the fatty acids palmitate and stearate. Contrast between the tumor and tissues, such as blood and muscle, increased in PET images acquired over a period of 120 min after [1-(11)C]acetate injection, and Patlak plots were linear from 17.5 min after injection. Similar results were obtained in a genetically engineered K-ras(G12D); p53(null) lung cancer model, in which the mean tumor-to-lung ratio at 90 min after [1-(14)C]acetate injection was 4.4-fold higher than at 15 min.


CONCLUSIONS
These findings suggest that when imaging de novo fatty acid synthesis with [1-(11)C]acetate it is preferable to measure uptake at later time points, when the effects of perfusion and (11)C incorporation into tricarboxylic acid cycle intermediates and bicarbonate are declining. The data presented here suggest that future clinical PET scans of tumors should be acquired later than 30 min, when tracer accumulation due to de novo fatty acid synthesis prevails.
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
David Y
DY
Lewis
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
Joan
J
Boren
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
Greg L
GL
Shaw
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
Robert
R
Bielik
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
Antonio
A
Ramos-Montoya
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom; and.
Timothy J
TJ
Larkin
MRC Cancer Unit, University of Cambridge, Cambridge, United Kingdom.
Carla P
CP
Martins
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
David E
DE
Neal
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
Dmitry
D
Soloviev
Cancer Research United Kingdom-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom; and kmb1001@cam.ac.uk.
Kevin M
KM
Brindle
D000085:Acetates; D000818:Animals; D002250:Carbon Radioisotopes; D005227:Fatty Acids / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D000085:Acetates; D002250:Carbon Radioisotopes; D005227:Fatty Acids
[11C]acetate PET; cancer; lung; mouse; prostate