title: Post-lumpectomy intracavitary retention and lymph node targeting of (⁹⁹m)Tc-encapsulated liposomes in nude rats with breast cancer xenograft.
abstract: 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 ((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 (⁹⁹m)Tc-BMEDA. Locoregional retention and systemic distribution of (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 (⁹⁹)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 (⁹⁹m)Tc was metabolized quickly and excreted into feces and urine, exerting low radiation burden on vital organs. In certain animals (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.
authors.affiliation: Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.forename: Beth
authors.initials: B
authors.lastname: Goins
authors.forename: William T
authors.initials: WT
authors.lastname: Phillips
authors.forename: Marcela
authors.initials: M
authors.lastname: Saenz
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Otto
authors.forename: Ande
authors.initials: A
authors.lastname: Bao
mesh_terms: D000818:Animals; D001918:Brachytherapy; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008081:Liposomes; D008198:Lymph Nodes / Q000378:metabolism*; D015412:Mastectomy, Segmental; D008856:Microscopy, Fluorescence; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D051381:Rats; D011923:Rats, Nude; D013667:Technetium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D013667:Technetium