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

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Abstract

Purpose

[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.

Procedures

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.

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Acknowledgments

This work was substantially supported by US National Institutes of Health/National Cancer Institute grant R01CA161209-05.

Author Contributions

Conceived and designed experiments: SAK, MMS, YK, AF, LC, and LLW. Performed the experiments: SAK, AF, LC, and KM. Analyzed the data: SAK, MMS, YK, AF, LC, KM, and LLW. Contributed materials/analysis tools: SAK, MMS, YK, AF, LC, and LLW. Writing and final manuscript approval: SAK, MMS, YK, AF, LC, KM, and LLW.

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Authors and Affiliations

  1. Hamamatsu/Queen’s PET Imaging Center, The Queen’s Medical Center, Honolulu, HI, USA

    Sandi A. Kwee

  2. Department of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, USA

    Sandi A. Kwee & Kyle Miyazaki

  3. Oncology Research, The Queen’s Medical Center, Honolulu, HI, USA

    Miles M. Sato

  4. Department of Medical Physics, University of Nevada Las Vegas, Las Vegas, NV, USA

    Yu Kuang

  5. University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA

    Adrian Franke, Laurie Custer & Linda L. Wong

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  1. Sandi A. Kwee
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  2. Miles M. Sato
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Correspondence to Sandi A. Kwee.

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The authors declare that they have no conflicts of interest.

Financial Support

This work was supported by NIH/NCI grant R01CA161209–05.

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Kwee, S.A., Sato, M.M., Kuang, Y. et al. [18F]Fluorocholine PET/CT Imaging of Liver Cancer: Radiopathologic Correlation with Tissue Phospholipid Profiling. Mol Imaging Biol 19, 446–455 (2017). https://doi.org/10.1007/s11307-016-1020-3

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