With the development of molecularly targeted cancer therapies, it is highly advantageous to be able to determine their efficacy to improve overall patient survival. Non-invasive imaging techniques are currently available for visualizing different pathological conditions of the human body, but their use for cancer monitoring is limited due to the lack of tumor-specific imaging probes. We have previously developed a multi-modal imaging probe (MN-EPPT) targeting the underglycosylated mucin-1 tumor antigen (uMUC-1), which is overexpressed and underglycosylated on over 90% of breast tumors and whose expression is tightly linked to tumor progression from pre-malignancy to advanced malignancy, as well as to tumor response to chemotherapy. In the past, we have shown that MN-EPPT is highly specific for uMUC-1 antigen and demonstrated its potential both for tumor detection in a variety of tumor models and for the tracking of change in tumor size following chemotherapy in a pre-clinical pancreatic cancer model. Our preliminary results extend these findings even further by defining a method for the simultaneous quantitative assessment of tumor volume and target antigen availability in breast tumors before and after chemotherapy. In this application, we propose to investigate the differential accumulation of MN-EPPT in human breast lesions at different stages of carcinogenesis, as a function of uMUC-1 availability, and to utilize this differential accumulation in order to noninvasively and quantitatively monitor the progression of the tumor from pre- malignancy to early malignancy, and finally to advanced malignancy. We will monitor two parameters of tumor progression: 1. change in tumor volume based on the tumor-selective uptake of the targeted probe which can be used for tumor delineation and 2. change in uMUC-1 antigen availability based on the specificity of MN- EPPT for the uMUC-1 antigen and expressed as differences in the amount of probe taken up by the tumor. Finally, we will evaluate change in tumor size and uMUC-1 expression during the course of conventional chemotherapy and correlate them with tumor progression/regression along the continuum from early to advanced malignancy. If successful, this study can further be translated into clinical applications, since related iron oxides have already been tested in clinical trials.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZCA1-SRRB-F (M1))
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Marks, Cheryl L
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Massachusetts General Hospital
United States
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Lo, Su-Tang; Pantazopouos, Pamela; Medarova, Zdravka et al. (2016) Presentation of underglycosylated mucin 1 in pancreatic adenocarcinoma (PDAC) at early stages. Am J Cancer Res 6:1986-1995
Wang, Ping; Yoo, Byunghee; Sherman, Sarah et al. (2016) Predictive imaging of chemotherapeutic response in a transgenic mouse model of pancreatic cancer. Int J Cancer 139:712-8
Ghosh, Subrata K; Uchida, Masashi; Yoo, Byunghee et al. (2013) Targeted imaging of breast tumor progression and therapeutic response in a human uMUC-1 expressing transgenic mouse model. Int J Cancer 132:1860-7
Ghosh, Subrata K; Pantazopoulos, Pamela; Medarova, Zdravka et al. (2013) Expression of underglycosylated MUC1 antigen in cancerous and adjacent normal breast tissues. Clin Breast Cancer 13:109-18
Medarova, Zdravka; Rashkovetsky, Leonid; Pantazopoulos, Pamela et al. (2009) Multiparametric monitoring of tumor response to chemotherapy by noninvasive imaging. Cancer Res 69:1182-9