Background: Hepatocellular carcinoma (HCC) remains a global health problem with unique diagnostic and\ntherapeutic challenges, including difficulties in identifying the highest risk patients. Previous work from our lab\nhas established the murine multidrug resistance-2 mouse (MDR2) model of HCC as a reasonable preclinical\nmodel that parallels the changes seen in human inflammatory associated HCC. The purpose of this study is to\nevaluate modalities of PET/CT in MDR2?/? mice in order to facilitate therapeutic translational studies from bench\nto bedside.\nMethods: 18F-FDG and 11C-acetate PET/CT was performed on 12 m MDR2?/? mice (n = 3/tracer) with HCC and 12 m\nMDR2?/+ control mice (n = 3/tracer) without HCC. To compare PET/CT to biological markers of HCC and cellular\nfunction, serum alpha-fetoprotein (AFP), lysophosphatidic acid (LPA), cAMP and hepatic tumor necrosis factor ?\n(TNF?) were quantified in 3-12 m MDR2?/? (n = 10) mice using commercially available ELISA analysis. To translate\nresults in mice to patients 11C-acetate PET/CT was also performed in 8 patents suspected of HCC recurrence following\ntreatment and currently on the liver transplant wait list.\nResults: Hepatic18F-FDG metabolism was not significantly increased in MDR2?/? mice. In contrast, hepatic 11C-acetate\nmetabolism was significantly elevated in MDR2?/? mice when compared to MDR2?/+ controls. Serum AFP and LPA\nlevels increased in MDR2?/? mice contemporaneous with the emergence of HCC. This was accompanied by a\nsignificant decrease in serum cAMP levels and an increase in hepatic TNF?. In patients suspected of HCC recurrence\nthere were 5 true positives, 2 true negatives and 1 suspected false 11C-acetate negative.\nConclusions: Hepatic 11C-acetate PET/CT tracks well with HCC in MDR2?/? mice and patients with underlying liver\ndisease. Consequently 11C-acetate PET/CT is well suited to study 1) HCC emergence/progression in patients and\n2) reduce animal numbers required to study new chemotherapeutics in murine models of HCC.
Loading....