| Targeted imaging of breast tumor progression and therapeutic response in a human uMUC-1 expressing transgenic mouse model. | |
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MedLine Citation:
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PMID: 23015160 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. We observed that tumor delta-T2s were significantly reduced by treatment with doxorubicin indicating lower accumulation of MN-EPPT. This correlated with a lower level of MUC-1 expression in the doxorubicin-treated tumors, as confirmed by immunoblotting. Our study could provide a very sensitive molecular imaging approach for monitoring tumor progression and therapeutic response. © 2012 Wiley Periodicals, Inc. |
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Authors:
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Subrata K Ghosh; Masashi Uchida; Byunghee Yoo; Alana W Ross; Sandra J Gendler; Jianlin Gong; Anna Moore; Zdravka Medarova |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-27 |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: - ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 UICC. |
Affiliation:
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Molecular Imaging Laboratory, MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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