Most diagnosed early stage breast cancer cases are treated by lumpectomy and adjuvant radiation therapy, which significantly decreases the locoregional recurrence but causes inevitable toxicity to normal tissue. By using a technique of preparing
liposomes carrying technetium-99m (
99mTc), rhenium-186 (
186Re), or rhenium-188 (
188Re) radionuc
lides, as well as chemotherapeutic agents, or their combination, for cancer therapy with real time image-monitoring of pharmacokinetics and prediction of therapy effect, this study investigated the potential of a novel targeted focal radiotherapy with low systemic toxicity using radioactive immuno
liposomes to treat both the surgical cavity and draining lymph nodes in a rat breast cancer xenograft positive surgical margin model. Immuno
liposomes modified with either panitumumab (anti-EGFR) or bevacizumab (anti-VEGF) were remote loaded with
99mTc diagnostic radionuc
lide, and injected into the surgical cavity of female nude rats with positive margins postlumpectomy. Locoregional retention and systemic distribution of
99mTc-immuno
liposomes were investigated by nuclear imaging, stereofluorescent microscopic imaging, and gamma counting. Histopathological examination of excised draining lymph nodes was performed. The locoregional retention of
99mTc-immuno
liposomes in each animal was influenced by the physiological characteristics of the surgical site of individual animals. Panitumumab- and bevacizumab-
liposome groups had higher intracavitary retention compared with the control
liposome groups. Draining lymph node uptake was influenced by both the intracavitary radioactivity retention level and metastasis status. The panitumumab-
liposome group had higher accumulation on the residual tumor surface and in the metastatic lymph nodes. Radioactive
liposomes that were cleared from the cavity were metabo
lized quickly and accumulated at low levels in vital organs. Therapeutic radionuc
lide-carrying specifically targeted panitumumab- and bevacizumab-
liposomes have increased potential compared to non-antibody targeted
liposomes for postlumpectomy focal therapy to eradicate remaining breast cancer cells inside the cavity and draining lymph nodes with low systemic toxicity.
Keywords:
breast cancer; targeted therapy; liposomes&qsSearchArea=searchText">immunoliposomes; intracavitary injection; metastasis