Delivery of gadolinium-labeled nanoparticles to the sentinel lymph node: Comparison of the sentinel node visualization and estimations of intra-nodal gadolinium concentration by the magnetic resonance imaging
Delivery of gadolinium-labeled nanoparticles to the sentinel lymph node: Comparison of the sentinel node visualization and estimations of intra-nodal gadolinium concentration by the magnetic resonance imaging
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DOI：
10.1016/j.jconrel.2005.12.019
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发表时间：
2006-04-10
影响因子：
10.8
通讯作者：
Choyke, PL
中科院分区：
文献类型：
--
作者：
Kobayashi, H;Kawamoto, S;Choyke, PL
前哨淋巴结成像通常在乳腺癌和黑色素瘤手术前进行。虽然目前的方法是基于放射性淋巴管造影，MR淋巴管造影（MRL）提供了更好的空间分辨率，没有电离辐射的好处。然而，用于前哨淋巴结成像的最佳纳米颗粒仍不清楚。评价直径范围为< 1至12 nm的钆标记（Gd）造影剂，以确定哪种尺寸提供了最快速和最集中的造影剂递送至淋巴转移小鼠模型中的淋巴结。具体地，比较了PAMAM-G2、PAMAM-G4、PAMAM-G6和PAMAM-G8以及DAB-G5 Gd-树枝状聚合物试剂，以及Gadomer-17和Gd-DTPA。在这些药剂中，G6 Gd树枝状聚合物描绘了具有最高峰浓度的淋巴管和淋巴结，并且这发生在注射后24-36分钟（p < 0.01;除G8外的所有）。基于离体浓度模型，Gd（III）离子在淋巴结内发生高积累（1.7-4.4 mM Gd/270-680 ppm Gd），具有高靶与背景比（> 100）。这些浓度足以考虑使用Gd-中子捕获治疗局部淋巴结。因此，当连续注射时，PAMAM-G6 Gd树枝状聚合物不仅提供了前哨淋巴结的极好的不透明化，而且还提供了前哨淋巴结靶向治疗的潜力。由爱思唯尔公司出版
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.