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The Use of Ligand Conjugated Superparamagnetic Iron Oxide Nanoparticles (SPION) for Early Detection of Metastases

C. Leuschner, C. Kumar, M.O. Urbina, J. Zhou, W. Soboyejo, W. Hansel and F. Hormes
Pennington Biomedical Research Center, US

Keywords:
metastases, nanoparticles, luteinizing hormone releasing hormone receptors, magnetic resonance imaging

Abstract:
Breast cancer is the most common cause of cancer death in women; more than 75 % of patients die from skeletal metastases. The accurate diagnosis of metastatic disease is therefore crucial for treatment and survival. We hypothesized that targeted delivery of SPIONs may facilitate and increase the accumulation of SPION in metastatic cancer cells in peripheral tissues, lymph nodes and bones, thus increasing the sensitivity of MR imaging. We previously demonstrated that breast cancers and their metastases can be targeted through their LHRH (luteinizing hormone releasing hormone) receptors. In this study we tested whether LHRH-SPION specifically target and accumulate in metastatic cells from breast cancer xenografts, thus increasing MRI sensitivity. Results: 1. LHRH-SPION were incorporated directly within the cancer cells of primary tumors and metastatic cells from peripheral tissues. 2. The amounts of LHRH-SPION accumulated were directly dependent on the number of metastatic cells, 3. Unconjugated SPION accumulated in the liver, showed poor affinity to the tumor and were not detectable in metastatic lesions; in contrast LHRH-SPION accumulated in the cytoplasm and nuclei of the target cells, 4. LHRH-SPION accumulated at higher concentrations in the tumor cells than SPION alone and 5. the contrast of the MR image was enhanced by LHRH-SPION. Conclusion: Because of the direct accumulation within the tumor cells LHRH conjugated SPION can serve as a contrast agent to specifically increase the sensitivity of detection of metastases and disseminated cells in lymph nodes, bones and peripheral organs by MRI.

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