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Cancers (Basel). 2019 Nov 7;11(11). pii: E1748. doi: 10.3390/cancers11111748.

[18F] Clofarabine for PET Imaging of Hepatocellular Carcinoma.

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Radiology, Case Western Reserve University, Cleveland, OH 44106, USA.
Nuclear Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Institute for Computational Biology, Cleveland, OH 44106, USA.
Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
Medical Oncology, Rowell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Hematology & Oncology, Cleveland Clinic, Cleveland, OH 44195, USA.


Clinical diagnosis of hepatocellular carcinoma (HCC) relies heavily on radiological imaging. However, information pertaining to liver cancer treatment such as the proliferation status is lacking. Imaging tumor proliferation can be valuable in patient management. This study investigated 18F-labeled clofarabine ([18F]CFA) targeting deoxycytidine kinase (dCK) for PET imaging of dCK-dependent proliferation in HCC. Since clinical PET scans showed a high liver background uptake of [18F]CFA, the aim of this study was to reduce this liver background uptake. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for imaging experiments. Several modifiers were tested and compared with the baseline PET scan: Forodesine, probenecid, and cold clofarabine, all applied before the hot [18F]CFA injection to evaluate the reduction in liver background uptake. Application of forodesine before hot [18F]CFA injection did not reduce the background uptake. Instead, it increased the background by 11.6-36.3%. Application of probenecid also increased the liver background uptake by 16.6-32.1%. Cold CFA application did reduce the liver background uptake of [18F]CFA, comparing to the baseline scan. Combining cold CFA with [18F]CFA for PET imaging of liver cancers is a promising strategy, worthy of further clinical evaluation.


PET imaging; hepatocellular carcinoma; tumor proliferation

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Conflict of interest statement

Y.S. holds patents and patent applications around decitabine, tetrahydrouridine, 5-azacytidine, and differentiation therapy agents to treat cancer with eligibility for royalties, ownership, board, and consultancy for EpiDestiny, none of which is a direct conflict of interest to the reported preclinical imaging study in this manuscript. All other authors declare that they have no competing interests.

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