title: [18F]Fluorocholine PET/CT Imaging of Liver Cancer: Radiopathologic Correlation with Tissue Phospholipid Profiling.
abstract: [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 positron emission tomography (PET)/x-ray computed tomography (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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Hamamatsu/Queen's PET Imaging Center, The Queen's Medical Center, Honolulu, HI, USA. kwee@hawaii.edu.|Department of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, USA. kwee@hawaii.edu.
authors: Sandi A
authors: SA
authors: Kwee
authors: Oncology Research, The Queen's Medical Center, Honolulu, HI, USA.
authors: Miles M
authors: MM
authors: Sato
authors: Department of Medical Physics, University of Nevada Las Vegas, Las Vegas, NV, USA.
authors: Yu
authors: Y
authors: Kuang
authors: University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
authors: Adrian
authors: A
authors: Franke
authors: University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
authors: Laurie
authors: L
authors: Custer
authors: Department of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, USA.
authors: Kyle
authors: K
authors: Miyazaki
authors: University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
authors: Linda L
authors: LL
authors: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000378:metabolism; D002794:Choline / Q000031:analogs & derivatives* / Q000737:chemistry; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism*; D000072078:Positron Emission Tomography Computed Tomography; D025341:Principal Component Analysis; D014057:Tomography, X-Ray Computed
chemical_list: D010743:Phospholipids; C514960:fluorocholine; D002794:Choline
keywords: Fatty acids; Fluorocholine; Hepatocellular carcinoma; Phosphatidylcholine; Positron emission tomography