Postlumpectomy loco-regional breast cancer therapy with liposomal therapeutic agents: Retention and distribution in nude rats

Abstract

e11562 Background: Post-lumpectomy loco-regional radiation therapy, such as brachytherapy, has been shown to decrease breast cancer recurrence and increase patient survival. Limitations of current brachytherapy are the relatively high radiation absorbed dose delivered to normal breast and the inability to treat potentially involved lymph nodes. Locally administered liposomes are being investigated for delivery of drugs and therapeutic radionuclides. We propose a new post-lumpectomy loco-regional therapy with liposome-carried therapeutic agents. To investigate, radiolabeled liposomes were injected into the surgical cavity of a nude rat model one day following surgical removal of the breast tumor, and in vivo retention and distribution were monitored with nuclear imaging and post- mortem dissection. Methods: Six liposome formulations containing 0.2% molar ratio Rhodamine B-lipid and cationic, neutral, or anionic surface charges were manufactured at diameters of 400 or 100 nm and characterized. Breast cancer xenograft model in female nude rats was set up by inoculating MDA-MB-231 cells into the fat pad of the left breast of each rat. When tumor volumes reached 1.9 cm3 on average, the majority of each tumor was surgically removed, leaving ∼0.05 cm3 tumor tissue in the cavity. Then, each rat (3–4 rats/group) was intracavitarily injected with 0.5 ml of 99mTc-liposomes (4 mCi., 30 mg total lipids/kg body weight). In vivo distribution of 99mTc-activity was measured with planar gamma camera and SPECT imaging at various times. Post-mortem stereo fluorescent images of surgical cavity and the surrounding lymph nodes at 44 h were acquired. Results: All 99mTc-liposome formulations had approximately ≥ 50% retention in the surgical cavity at 44 h after injection. 99mTc-anionic liposomes of 100 nm diameter had an optimal lymph node targeting with ∼6%/g tissue in the surrounding lymph nodes at 44 h. Fluorescence imaging of the liposomes clearly showed their clearance through surrounding lymphatics and retention in lymph nodes. Conclusions: Anionic liposomes of 100 nm diameter are promising carriers for the simultaneous treatment of the surgical cavity and its draining lymph nodes. No significant financial relationships to disclose.