Multimodal In Vivo Imaging of Tumorigenesis and Response to Chemotherapy in a Transgenic Mouse Model of Mammary Cancer

Mol Imaging Biol. 2016 Aug;18(4):617-26. doi: 10.1007/s11307-015-0916-7.


Purpose: Transgenic mice expressing the polyoma middle T oncoprotein (PyMT) in the mammary epithelium were explored by multimodal imaging to monitor longitudinally spontaneous tumor growth and response to chemotherapy.

Procedures: Positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), single photon emission tomography (SPECT) with [(99m)Tc]TcO4 ([(99m)Tc]TEC), X-ray computed tomography, and fluorescent confocal endomicroscopy (FCE) images were acquired during tumor progression in female PyMT mice. Imaging with [(18)F]FDG and [(99m)Tc]TEC was also performed in untreated, doxorubicin-treated, and docetaxel-treated PyMT mice. Total tumor volumes were quantified. Tumors were collected and macroscopic and histological examinations were performed.

Results: All PyMT mice developed multifocal tumors of the mammary epithelium that became palpable at 8 weeks of age (W8). Computed tomography (CT) detected tumors at W14, while a clear tumoral uptake of [(99m)Tc]TEC and [(18)F]FDG was present as early as W6 and W8, respectively. No contrast between mammary tumors and surrounding tissue was observed at any stage with [(18)F]FLT. FCE detected an angiogenic switch at W10. Lung metastases were not clearly evidenced by imaging. Doxorubicin and docetaxel treatments delayed tumor growth, as shown by [(18)F]FDG and [(99m)Tc]TEC, but tumor growth resumed upon treatment discontinuation. Tumor growth fitted an exponential model with time constant rates of 0.315, 0.145, and 0.212 week(-1) in untreated, doxorubicin, and docetaxel groups, respectively.

Conclusions: Molecular imaging of mammary tumors in PyMT is precocious, precise, and predictive. [(18)F]FDG-PET and [(99m)Tc]TEC SPECT monitor tumor response to chemotherapy.

Keywords: Biomarker; Breast cancer; Molecular imaging; Response to treatment; Sodium-iodide symporter; Transgenic model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinogenesis / pathology*
  • Cell Proliferation
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Fluorescence
  • Fluorodeoxyglucose F18
  • Ki-67 Antigen / metabolism
  • Mammary Neoplasms, Animal / blood supply
  • Mammary Neoplasms, Animal / diagnostic imaging
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Mice, Transgenic
  • Multimodal Imaging / methods*
  • Technetium / chemistry
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed


  • Antineoplastic Agents
  • Ki-67 Antigen
  • Fluorodeoxyglucose F18
  • Technetium