title: Comparative functional evaluation of immunocompetent mouse breast cancer models established from PyMT-tumors using small animal PET with [(18)F]FDG and [(18)F]FLT.
abstract: Positron emission tomography (PET) allows detection of functional changes in malignant tissue. Establishment of an immortalized immunocompetent breast cancer mouse model would provide a useful platform for the analysis of novel cancer treatment strategies. This study describes a comparative functional evaluation of murine breast cancer models established from polyoma virus middle T antigen (PyMT)-derived tumors using small animal PET imaging with [(18)F]FDG and [(18)F]FLT. Primary PyMT tumor-derived cells and a cell line derived from these tumors (MTHJ) were injected subcutaneously into immunocompetent FVB mice to generate breast cancer xenografts. Tumor growth rates were comparable in both models and tumors were analyzed after 4-5 weeks post-injection. [(18)F]FDG uptake in vitro followed a comparable trend in both models but reached higher uptake levels in primary PyMT cells vs. MTHJ cells after 120 min. At all time points, [(18)F]FLT uptake was significantly higher in MTHJ compared to primary PyMT cells. Dynamic small animal PET imaging with [(18)F]FDG revealed standardized uptake values (SUVs) of 2.5±0.1 (n=8) in tumors from primary cells and 2.8±0.4 (n=6) in MTHJ tumors after 60 min p.i.. The corresponding tumor-muscle-ratios were 9.3±1.5 and 10.4±0.9, respectively. Uptake of [(18)F]FLT resulted in slightly higher SUV(60min) in MTHJ tumors (1.1±0.1, n=6) compared to tumors from primary cells (SUV(60min)=0.9±0.05, n=8, p=0.07). The tumor-muscle-ratio was comparable in both tumors (2.1±0.2 and 1.8±0.1, respectively). The PET imaging data demonstrates that the functional profile of immunocompetent murine breast tumor model MTHJ remains the same as in primary-derived PyMT tumors in vivo. Metabolic and proliferative rates as assessed with [(18)F]FDG and [(18)F]FLT are comparable in both tumor models. The observed high SUV(60min) of 2.8±0.4 with [(18)F]FDG in MTHJ tumors allows one to monitor efficacy of therapeutic interventions connected with changes in metabolic response of the tumor by means of small animal PET.
authors.affiliation: Department of Oncology, University of Alberta - Cross Cancer Institute Edmonton, AB - T6G 1Z2, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Desilva
authors.forename: Melinda
authors.initials: M
authors.lastname: Wuest
authors.forename: Monica
authors.initials: M
authors.lastname: Wang
authors.forename: Jeff
authors.initials: J
authors.lastname: Hummel
authors.forename: Karen
authors.initials: K
authors.lastname: Mossman
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
authors.forename: Mary M
authors.initials: MM
authors.lastname: Hitt
keywords: PET; Polyoma virus middle T antigen (PyMT); [18F]FDG; [18F]FLT; breast cancer; mouse model