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Am J Nucl Med Mol Imaging 2012;2(1):88-98
Original Article
Comparative functional evaluation of immunocompetent mouse breast cancer
models established from PyMT-tumors using small animal PET with [18F]FDG and
[18F]FLT
Alan DeSilva, Melinda Wuest, Monica Wang, Jeff Hummel, Karen Mossman, Frank Wuest, Mary M. Hitt
Department of Oncology, University of Alberta – Cross Cancer Institute, Edmonton, AB – T6G 1Z2, Canada; Department of Pathology
and Molecular Medicine, McMaster University, Hamilton, ON – L8N 3Z5, Canada.
Received October 21, 2011; accepted November 10, 2011; Epub December 15, 2011; Published January 1, 2011
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 [18F]FDG and [18F]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. [18F]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, [18F]FLT uptake was significantly higher in MTHJ compared to
primary PyMT cells. Dynamic small animal PET imaging with [18F]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 [18F]FLT resulted in slightly higher SUV60min in MTHJ tumors (1.1 +- 0.1, n = 6)
compared to tumors from primary cells (SUV60min = 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 [18F]FDG and [18F]FLT are comparable in both tumor models. The observed high SUV60min of 2.8 +- 0.4 with [18F]
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. (ajnmmi1110002).
Keywords: Polyoma virus middle T antigen (PyMT), breast cancer, PET, [18F]FDG, [18F]FLT, mouse model
Full text PDF
Address all correspondence to:
Frank Wuest, PhD
Department of Oncology
Cross Cancer Institute
11560 University Ave
Edmonton, Alberta
Canada T6G 1Z2
E-mail: wuest@ualberta.ca
Original Article
Comparative functional evaluation of immunocompetent mouse breast cancer
models established from PyMT-tumors using small animal PET with [18F]FDG and
[18F]FLT
Alan DeSilva, Melinda Wuest, Monica Wang, Jeff Hummel, Karen Mossman, Frank Wuest, Mary M. Hitt
Department of Oncology, University of Alberta – Cross Cancer Institute, Edmonton, AB – T6G 1Z2, Canada; Department of Pathology
and Molecular Medicine, McMaster University, Hamilton, ON – L8N 3Z5, Canada.
Received October 21, 2011; accepted November 10, 2011; Epub December 15, 2011; Published January 1, 2011
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 [18F]FDG and [18F]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. [18F]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, [18F]FLT uptake was significantly higher in MTHJ compared to
primary PyMT cells. Dynamic small animal PET imaging with [18F]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 [18F]FLT resulted in slightly higher SUV60min in MTHJ tumors (1.1 +- 0.1, n = 6)
compared to tumors from primary cells (SUV60min = 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 [18F]FDG and [18F]FLT are comparable in both tumor models. The observed high SUV60min of 2.8 +- 0.4 with [18F]
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. (ajnmmi1110002).
Keywords: Polyoma virus middle T antigen (PyMT), breast cancer, PET, [18F]FDG, [18F]FLT, mouse model
Full text PDF
Address all correspondence to:
Frank Wuest, PhD
Department of Oncology
Cross Cancer Institute
11560 University Ave
Edmonton, Alberta
Canada T6G 1Z2
E-mail: wuest@ualberta.ca
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