Evaluation of 11C-Acetate and 18 F-FDG PET/CT in mouse multidrug resistance gene-2 deficient mouse model of hepatocellular carcinoma

Paul R. Territo, Mary Maluccio, Amanda A. Riley, Brian P. McCarthy, James Fletcher, Mark Tann, Romil Saxena, Nicholas J. Skill

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

Original languageEnglish (US)
Article number15
JournalBMC Medical Imaging
Issue number1
StatePublished - May 16 2015

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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