BACKGROUND
[18F]fluorocholine PET/CT can detect
hepatocellular carcinoma (HCC) based on imaging the initial steps of
phosphatidylcholine synthesis. To relate the diagnostic performance of
[18F]fluorocholine PET/CT to the phospholipid
composition of liver tumors, radiopathologic correspondence was performed in
patients with early-stage liver cancer who had undergone
[18F]fluorocholine PET/CT before tumor
resection.
METHODS
Tumor and adjacent liver were profiled by liquid chromatography mass
spectrometry, quantifying phosphatidylcholine species by mass-to-charge
ratio. For clinical-radiopathologic correlation, HCC profiles were reduced
to two orthogonal principal component factors (PCF1 and PCF2) accounting for
80% of total profile variation.
RESULTS
Tissues from 31 HCC patients and 4 intrahepatic cholangiocarcinoma
(ICC) patients were analyzed, revealing significantly higher levels of
phosphocholine, CDP-choline, and highly-saturated phosphatidylcholine
species in HCC tumors relative to adjacent liver and ICC tumors. Significant
loading values for PCF1 corresponded to phosphatidylcholines containing
poly-unsaturated fatty acids while PCF2 corresponded only to
highly-saturated phosphatidylcholines. Only PCF2 correlated significantly
with HCC tumor-to-liver [18F]fluorocholine uptake
ratio (ρ = 0.59, p < 0.0005). Sensitivity for all
tumors based on an abnormal [18F]fluorocholine
uptake ratio was 93%, while sensitivity for HCC based on increased
tumor [18F]fluorocholine uptake was 84%,
with lower levels of highly-saturated phosphatidylcholines in tumors showing
low [18F]fluorocholine uptake.
CONCLUSION
Most HCC tumors contain high levels of saturated
phosphatidylcholines, supporting their dependence on de-novo fatty acid
metabolism for phospholipid membrane synthesis. While
[18F]fluorocholine PET/CT can serve to identify
these lipogenic tumors, its imperfect diagnostic sensitivity implies
metabolic heterogeneity across HCC and a weaker lipogenic phenotype in some
tumors.