TY - JOUR
T1 - Post-lumpectomy intracavitary retention and lymph node targeting of 99mTc-encapsulated liposomes in nude rats with breast cancer xenograft
AU - Li, Shihong
AU - Goins, Beth
AU - Phillips, William T.
AU - Saenz, Marcela
AU - Otto, Pamela M.
AU - Bao, Ande
N1 - Funding Information:
Acknowledgments This research was supported by Susan G. Komen for the Cure® research grant, BCTR0707169 and partly supported by NIH/NCI grant, R01 CA131039. Fluorescent stereomicroscopic images were generated in the Core Optical Imaging Facility which was supported by UTHSCSA, NIH-NCI P30 CA54174 (San Antonio Cancer Institute), NIH-NIA P30 AG013319 (Nathan Shock Center), and (NIH-NIA P01AG19316).
PY - 2011/11
Y1 - 2011/11
N2 - 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 (99mTc) 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 99mTc-BMEDA. Locoregional retention and systemic distribution of 99mTc-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 99mTc-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 99mTc was metabolized quickly and excreted into feces and urine, exerting low radiation burden on vital organs. In certain animals 99mTc-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 treatmentof the surgical cavity and the draining lymph nodes of early-stage breast cancer.
AB - 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 (99mTc) 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 99mTc-BMEDA. Locoregional retention and systemic distribution of 99mTc-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 99mTc-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 99mTc was metabolized quickly and excreted into feces and urine, exerting low radiation burden on vital organs. In certain animals 99mTc-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 treatmentof the surgical cavity and the draining lymph nodes of early-stage breast cancer.
KW - Brachytherapy
KW - Breast cancer
KW - Intracavitary
KW - Locoregional retention
KW - Lymph node
KW - Radioactive liposomes
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U2 - 10.1007/s10549-010-1309-x
DO - 10.1007/s10549-010-1309-x
M3 - Article
C2 - 21181436
AN - SCOPUS:82455218977
SN - 0167-6806
VL - 130
SP - 97
EP - 107
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -