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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8 Scopus citations

Abstract

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
Volume15
Issue number1
DOIs
StatePublished - May 16 2015

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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