Evaluation of 11C-Acetate and 18 F-FDG PET/CT in mouse multidrug resistance gene-2 deficient mouse model of hepatocellular carcinoma
dc.contributor.author | Territo, Paul R. | |
dc.contributor.author | Maluccio, Mary | |
dc.contributor.author | Riley, Amanda A. | |
dc.contributor.author | McCarthy, Brian P. | |
dc.contributor.author | Fletcher, James | |
dc.contributor.author | Tann, Mark | |
dc.contributor.author | Saxena, Romil | |
dc.contributor.author | Skill, Nicholas J. | |
dc.contributor.department | Department of Radiology and Imaging, IU School of Medicine | en_US |
dc.date.accessioned | 2015-07-10T19:47:53Z | |
dc.date.available | 2015-07-10T19:47:53Z | |
dc.date.issued | 2015-05 | |
dc.description.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−/− mice in order to facilitate therapeutic translational studies from bench to bedside. Methods 18F-FDG and 11C-acetate PET/CT was performed on 12 m MDR2−/− mice (n = 3/tracer) with HCC and 12 m MDR2−/+ 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−/− (n = 10) mice using commercially available ELISA analysis. To translate results in mice to patients 11C-acetate PET/CT was also performed in 8 patents suspected of HCC recurrence following treatment and currently on the liver transplant wait list. Results Hepatic18F-FDG metabolism was not significantly increased in MDR2−/− mice. In contrast, hepatic 11C-acetate metabolism was significantly elevated in MDR2−/− mice when compared to MDR2−/+ controls. Serum AFP and LPA levels increased in MDR2−/− 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 11C-acetate negative. Conclusions Hepatic 11C-acetate PET/CT tracks well with HCC in MDR2−/− mice and patients with underlying liver disease. Consequently 11C-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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Territo, P. R., Maluccio, M., Riley, A. A., McCarthy, B. P., Fletcher, J., Tann, M., ... & Skill, N. J. (2015). Evaluation of 11C-Acetate and 18 F-FDG PET/CT in mouse multidrug resistance gene-2 deficient mouse model of hepatocellular carcinoma. BMC medical imaging, 15(1), 15. | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/6546 | |
dc.language.iso | en_US | en_US |
dc.publisher | BioMed Central | en_US |
dc.relation.isversionof | 10.1186/s12880-015-0058-z | en_US |
dc.relation.journal | BMC Medical Imaging | en_US |
dc.rights | Attribution 3.0 United States | |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | |
dc.source | PMC | en_US |
dc.subject | Hepatocellular carcinoma | en_US |
dc.subject | 11C-Acetate | en_US |
dc.subject | 18 F-FDG PET/CT | en_US |
dc.title | Evaluation of 11C-Acetate and 18 F-FDG PET/CT in mouse multidrug resistance gene-2 deficient mouse model of hepatocellular carcinoma | en_US |
dc.type | Article | en_US |