Tc-99m Labeled and VIP-Receptor Targeted Liposomes for Effective Imaging of Breast Cancer

摘要

However, current methods of breast cancer detection cannot provide accurate results. This study was conceived to begin to address this issue by developing and testing a novel method of active targeting of radionuclide (Tc- 99m) encapsulating sterically stabilized liposomes (SSL) for gamma scintigraphic imaging of breast cancer. This non-invasive imaging modality utilizes both overexpression of vasoactive intestinal peptide (VIP) receptors in breast tumor and distinct biology of the tumors (leaky vasculature) to target specifically to breast cancer. The liposomal imaging agent developed in this study encapsulates multiple molecules of Tc99m for high sensitivity. In addition, its specificity for breast cancer is achieved with a peptide (VIP) the receptors of which are over expressed in breast cancer. Targeting of this novel liposomal imaging agent to breast tumors was tested both in vitro using rat and human breast cancer tissues and in vivo using a carcinogen induced rat breast cancer model. The results showed that significantly more VIP-SSL were bound to carcinogen-induced rat breast cancer tissue sections than SSL without VIP or with non-covalently associated VIP. The imaging results demonstrated that Tc-99m encapsulating VIP-SSL showed a higher tumor-to-background ratio than Tc-99m encapsulating SSL. In addition, the accumulation of Tc-99m encapsulating VIP-SSL was significantly higher than Tc-99m encapsulating SSL in rat breast tumor, suggesting that the presence of VIP did serve the purpose of active targeting of liposomes, confirming the results obtained by imaging studies. In conclusion, the novel breast tumor targeted liposomes developed in this study can provide accurate detection of breast cancer in the clinics. In addition, the same targeted carrier system can be used in the future for the targeted delivery of anticancer agents to breast tumors for safe and effective chemotherapy of breast cancer.