Novel Method to Label Solid Lipid Nanoparticles with 64Cu for Positron Emission Tomography Imaging
Novel Method to Label Solid Lipid Nanoparticles with 64Cu for Positron Emission Tomography Imaging
复制标题
DOI：
10.1021/bc100478k
复制
发表时间：
2011-04-01
影响因子：
4.7
通讯作者：
Louie, Angelique
中科院分区：
文献类型：
--
作者：
Andreozzi, Erica;Seo, Jai Woong;Louie, Angelique
固体脂质纳米粒（SLN）是近十年来发展起来的亚微米（1- 1000 nm）胶体载体，作为传统载体（乳剂、脂质体和聚合物纳米粒）的替代系统，用于静脉内应用。由于SLN作为药物载体的潜力，人们对了解SLN在静脉内（i. v.）注射正电子发射断层扫描（PET）是一种有吸引力的方法，用于研究生物分布，但需要放射性标记的化合物。在这项工作中，我们描述了一种方法来放射性标记SLN在体内PET研究。将与合成脂质缀合的铜特异性螯合剂6[对-（溴乙酰氨基）-苄基]-1，4，8，11-四氮杂环十四烷-N，N“，N”“，N”"-四乙酸（BAT）掺入SLN中。在25 ℃下在0.1M NH 40 Ac缓冲液（pH 5.5）中与（CuCl 2）-Cu-64孵育1小时后，SLN（类似于150 nm）成功地用Cu-61放射性标记（66.5%放射性标记产率），在纯化后显示>95%放射性标记的颗粒。将Cu-64-SLN静脉注射给小鼠，并在注射后0.5、3、20和48小时用PET成像。成像后使用伽马计数确认器官分布。通过图像定量分析获得的组织放射性（%注射剂量/克，%ID/g）表明，Cu-64-SLN在3 h后在血流中循环（血液半衰期类似于1.4 h），但在48 h时几乎完全清除。PET和γ计数表明，在注射后48小时，约5-7%ID/g Cu-64-SLN保留在肝脏中。稳定性试验证实，铜在48小时内仍然与SLN结合，并且观察到的生物分布模式不是来自游离的、解离的铜。我们的研究结果表明，SLN可以用Cu-64进行放射性标记，其生物分布可以通过体内PET成像和离体γ计数进行定量评估。
Solid lipid nanoparticles (SLNs) are submicrometer (1-1000nm) colloidal carriers developed in the past decade as an alternative system to traditional carriers (emulsions, liposomes, and polymeric nanoparticles) for intravenous applications. Because of their potential as drug carriers, there is much interest in understanding the in vivo biodistribution of SLNs following intravenous (i.v.) injection. Positron emission tomography (PET) is an attractive method for investigating biodistribution but requires a radiolabeled compound. In this work, we describe a method to radiolabel SLN for in vivo PET studies. A copper specific chelator, 6[p-(bromoacetamido)-benzyl]-1,4,8,11-tetraazacyclotetradecan-N,N',N '',N'''-tetraacetic acid (BAT), conjugated with a synthetic lipid, was incorporated into the SLN. Following incubation with (CuCl2)-Cu-64 for 1 h at 25 degrees C in 0.1 M NH4OAc buffer (pH 5.5), the SLNs (similar to 150 nm) were successfully radiolabeled with Cu-61 (66.5% radiolabeling yield), exhibiting >95% radiolabeled particles following purification. The Cu-64-SLNs were delivered intravenously to mice and imaged with PET at 0.5, 3, 20, and 48 h post injection. Gamma counting was utilized post imaging to confirm organ distributions. Tissue radioactivity (% injected dose/gram, %ID/g), obtained by quantitative analysis of the images, suggests that the Cu-64-SLNs are circulating in the bloodstream after 3 h (blood half-life similar to 1.4 h), but are almost entirely cleared by 48 h. PET and gamma counting demonstrate that approximately 5-7%ID/g Cu-64-SLNs remain in the liver at 48 h post injection. Stability assays confirm that copper remains associated with the SLN over the 48 h time period and that the biodistribution patterns observed are not from free, dissociated copper. Our results indicate that SLNs can be radiolabeled with Cu-64, and their biodistribution can be quantitatively evaluated by in vivo PET imaging and ex vivo gamma counting.