[18F]Fluorocholine PET/CT Imaging of Liver Cancer: Radiopathologic Correlation with Tissue Phospholipid Profiling

Abstract

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.

Levels of choline‐containing compounds in normal liver and liver metastases of colorectal cancer as recorded by 1H MRS

“…These studies did not include a particular motion correction procedure in the examination or analysis. Phospholipid profiling of biopsies showed a significantly increased PCho level in hepatocellular carcinoma compared with normal liver . However, a 1 H MRS study on mostly metastatic tumors in the liver that included motion correction by acquisition during breath holding and frequency and phase correction of individual sequential spectra did not detect a difference with normal liver tissue, with only a trend to a lower tCho to water ratio …”

[18F]-choline PET/CT as an imaging biomarker for primary liver cancers

“…To be an imaging biomarker, a quick static PET scan with fluorocholine along with simpler quantification is certainly desirable for routine use in a clinical setting. The recent clinical study confirmed that compartmental modeling using the dynamically acquired PET imaging data and the resultant parameter (k 1 –k 4 ) estimation added no further or better correlation with the profiling data [Table 4 in (8)]. That can be explained in part by the fact that lipid profiling performed in this recent study was based on endogenous lipids, not radio-metabolite analysis of the radiotracer with its transient or intermediate products.…”

“…(8). Tumor and adjacent liver tissues were profiled by liquid chromatography mass spectrometry, and different molecular species of PC quantified by mass-to-charge ratio.…”

“…The main issue with choline tracers might still be the high liver background, which the data from the recent study indirectly addressed (8). No easy solution is in sight.…”

“…A unique clinical study was published recently by Kwee et al ., correlating fluorocholine PET imaging data with phospholipid profiling (8). This study is different from most previous published clinical studies on the same topic (9–11).…”