The overall goal of this proposal is to design, synthesize and test a novel multi-modal imaging probe specifically recognizing in vivo tumors expressing underglycosylated mucin-1 antigen (uMAC-1), which is one of the early hallmarks of tumorogenesis in wide variety of tumors. If developed, these probes will greatly aid in screening prospective patients for early cancer detection, and in monitoring the efficacy of drug therapy and tumor re-occurrence. With the recent development of new crosslinked superparamagnetic dextran coated iron oxide nanoparticles (CLIO) for MR imaging and near-infrared probes (Cy5.5 dye) for optical imaging, it became possible to design multi-modal imaging probes that would combine the advantages of both methods. MUC-1 is overexpressed and underglycosylated on almost all human epithelial cell adenocarcinomas, including more than 90% of human breast cancers, pancreatic, colorectal, lung, prostate, colon and gastric carcinomas. Moreover, uMUC-1 expression has been demonstrated in non-epithelial cancer cell-lines, as well as in hematological malignancies such as multiple myeloma and some B-cell non-Hodgkin lymphomas. In this study we propose to synthesize the imaging probe that consists of CLIO nanoparticles, modified with Cy5.5 fluorochrome and has peptides, specifically recognizing uMUC-1, attached to its dextran coat. In our preliminary experiments we synthesized such a probe and tested its specificity in vitro. Furthermore, in our initial imaging experiments in vivo we were able to see accumulation of the probe in the mouse model of human cancer. If successful, this study can be further translated into clinical applications since related iron oxides have already been tested in clinical trials.
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| Medarova, Zdravka; Pham, Wellington; Kim, Young et al. (2006) In vivo imaging of tumor response to therapy using a dual-modality imaging strategy. Int J Cancer 118:2796-802 |
| Pham, Wellington; Medarova, Zdravka; Moore, Anna (2005) Synthesis and application of a water-soluble near-infrared dye for cancer detection using optical imaging. Bioconjug Chem 16:735-40 |
| Moore, Anna; Medarova, Zdravka; Potthast, Andreas et al. (2004) In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe. Cancer Res 64:1821-7 |
