Post-lumpectomy intracavitary retention and lymph node targeting of ^sup 99m^Tc-encapsulated liposomes in nude rats with breast cancer xenograft

• Published in: Breast cancer research and treatment 2011-11, Vol.130 (1), p.97
• Main Authors: Li, Shihong, Goins, Beth, Phillips, William T, Saenz, Marcela, Otto, Pamela M, Bao, Ande
• Format: Article
• Language: English
• Subjects: Breast cancer; Cancer research; Cancer therapies; Drug delivery systems; Lymphatic system; Radiation therapy; Rodents
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-010-1309-x

Liposomes are recognized drug delivery systems with tumor-targeting capability. In addition, therapeutic or diagnostic radionuclides can be efficiently loaded into liposomes. This study investigated the feasibility of utilizing radiotherapeutic liposomes as a new post-lumpectomy radiotherapy for early-stage breast cancer by determining the locoregional retention and systemic distribution of liposomes radiolabeled with technetium-99m (^sup 99m^Tc) in an orthotopic MDA-MB-231 breast cancer xenograft nude rat model. To test this new brachytherapy approach, a positive surgical margin lumpectomy model was set up by surgically removing the xenograft and deliberately leaving a small tumor remnant in the surgical cavity. Neutral, anionic, and cationic surface-charged fluorescent liposomes of 100 and 400 nm diameter were manufactured and labeled with ^sup 99m^Tc-BMEDA. Locoregional retention and systemic distribution of ^sup 99m^Tc-liposomes injected into the post-lumpectomy cavity were determined using non-invasive nuclear imaging, ex vivo tissue gamma counting and fluorescent stereomicroscopic imaging. The results indicated that ^sup 99m^Tc-liposomes were effectively retained in the surgical cavity (average retention was 55.7 ± 24.2% of injected dose for all rats at 44 h post-injection) and also accumulated in the tumor remnant (66.9 ± 100.4%/g for all rats). The majority of cleared ^sup 99m^Tc was metabolized quickly and excreted into feces and urine, exerting low radiation burden on vital organs. In certain animals ^sup 99m^Tc-liposomes significantly accumulated in the peripheral lymph nodes, especially 100 nm liposomes with anionic surface charge. The results suggest that post-lumpectomy intracavitary administration of therapeutic radionuclides delivered by 100-nm anionic liposome carrier is a potential therapy for the simultaneous treatment of the surgical cavity and the draining lymph nodes of early-stage breast cancer.[PUBLICATION ABSTRACT]