Targeted imaging of breast tumor progression and therapeutic response in a human uMUC-1 expressing transgenic mouse model

Subrata K. Ghosh, Masashi Uchida, Byunghee Yoo, Alana W. Ross, Sandra J. Gendler, Jianlin Gong, Anna Moore, Zdravka Medarova

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The ability to monitor breast cancer initiation and progression on the molecular level would provide an effective tool for early diagnosis and therapy. In the present study, we focused on the underglycosylated MUC-1 tumor antigen (uMUC-1), which is directly linked to tumor progression from pre-malignancy to advanced malignancy in breast cancer and has been identified as the independent predictor of local recurrence and tumor response to chemotherapy. We investigated whether changes in uMUC-1 expression during tumor development and therapeutic intervention could be monitored non-invasively using molecular imaging approach with the uMUC-1-specific contrast agent (MN-EPPT) detectable by magnetic resonance and fluorescence optical imaging. This was done in mice that express human uMUC-1 tumor antigen (MMT mice) and develop spontaneous mammary carcinoma in a stage-wise fashion. After the injection of MN-EPPT there was a significant reduction in average T2 relaxation times of the mammary fat pad between pre-malignancy and cancer. In addition, T2 relaxation times were already altered at pre-malignant state in these mice compared to non-tumor bearing mice. This indicated that targeting uMUC-1 could be useful for detecting pre-malignant transformation in the mammary fat pad. We also probed changes in uMUC-1 expression with MN-EPPT during therapy with doxorubicin (Dox). We observed that tumor delta-T2s were significantly reduced by treatment with Dox indicating lower accumulation of MN-EPPT. This correlated with a lower level of MUC-1 expression in the Dox-treated tumors, as confirmed by immunoblotting. Our study could provide a very sensitive molecular imaging approach for monitoring tumor progression and therapeutic response. What's new? The ability to monitor breast cancer initiation and progression on the molecular level would provide an effective tool for early diagnosis and therapy. Here the authors focused on the underglycosylated MUC-1 tumor antigen (uMUC-1), which is directly linked to breast cancer progression and tumor response to chemotherapy. They showed that changes in uMUC-1 expression during tumor development and therapeutic intervention could be monitored non-invasively using a molecular imaging approach with the uMUC-1-specific contrast agent. The work could provide a very sensitive molecular approach for monitoring tumor progression and therapeutic response as well as identifying pre-malignancy in breast cancer.

Original languageEnglish (US)
Pages (from-to)1860-1867
Number of pages8
JournalInternational Journal of Cancer
Volume132
Issue number8
DOIs
StatePublished - Apr 15 2013

Keywords

  • antigen downregulation
  • breast cancer
  • molecular imaging
  • target-specific contrast agent
  • underglycosylated MUC-1 antigen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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