期刊
JOURNAL OF CONTROLLED RELEASE
卷 111, 期 3, 页码 343-351出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2005.12.019
关键词
breast cancer; MRI; sentinel lymph node; nanoparticle; gadolinium neutron capture therapy
资金
- Intramural NIH HHS Funding Source: Medline
Sentinel node imaging is commonly performed prior to surgery for breast cancer and melanoma. While current methods are based on radio-lymphoscintigraphy, MR lymphangiography (MRL) offers the benefits of better spatial resolution without ionizing radiation. However, the optimal nanoparticle for imaging the sentinel nodes remains unclear. Gadolinium-labeled (Gd) contrast agents ranging in diameter from < 1 to 12 nm were evaluated to determine which size provides the most rapid and most concentrated delivery of contrast agent to the lymph nodes in a mouse model of lymphatic metastases. Specifically, PAMAM-G2, -G4, -G6 and -G8, and DAB-G5 Gd-dendrimer agents, as well as Gadomer-17 and Gd-DTPA, were compared. Among these agents, the G6 Gd dendrimer depicted the lymphatics and lymph nodes with the highest peak concentrations and this occurred 24-36 min post-injection (p < 0.01; all except G8). Based on ex vivo concentration phantoms, high accumulations of Gd(III) ions occurred within lymph nodes (1.7-4.4 mM Gd/270-680 ppm Gd) with high target to background ratios (> 100). These concentrations are sufficient to contemplate the use of Gd-neutron capture therapy of regional lymph nodes. Thus, when injected interstitially, the PAMAM-G6 Gd dendrimer not only provides excellent opacification of sentinel lymph nodes, but also provides the potential for targeted therapy of sentinel lymph nodes. Published by Elsevier B.V.
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