A modular labeling strategy for in vivo PET and near-infrared fluorescence imaging of nanoparticle tumor targeting.
A modular labeling strategy for in vivo PET and near-infrared fluorescence imaging of nanoparticle tumor targeting.
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DOI：
10.2967/jnumed.114.141861
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Reiner T
中科院分区：
文献类型：
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作者：
Pérez-Medina C;Abdel-Atti D;Zhang Y;Longo VA;Irwin CP;Binderup T;Ruiz-Cabello J;Fayad ZA;Lewis JS;Mulder WJ;Reiner T
临床前分子成像的进展为非侵入性地可视化纳米颗粒治疗剂的生物分布和肿瘤靶向提供了新的机会。利用这一领域的最新成就，我们试图开发一种基于89 Zr的标记策略，用于通过被动靶向机制在肿瘤中积累的脂质体纳米颗粒。使用2种不同的方法制备89 Zr标记的脂质体：点击标记和表面螯合。在乳腺癌小鼠模型上进行了药物动力学和生物分布研究，以及放射性标记纳米颗粒的PET/CT成像。此外，通过掺入近红外荧光团制备了双PET/光学探针，并通过PET和近红外荧光成像在体内进行了测试。表面螯合方法证明在放射化学产率和稳定性以及体内性能方面具有上级优势。这些脂质体在肿瘤中的累积在注射后24小时达到峰值，并且测量为13.7 ± 1.8%注射剂量/gram。该探针的体内性能基本上不受近红外荧光团掺入的干扰。我们已经开发了一种高度模块化和有效的策略，用于标记脂质体纳米颗粒与89 Zr。在乳腺癌的异种移植和原位小鼠模型中，我们证明了这些纳米颗粒的生物分布可以通过PET成像可视化。与近红外染料组合，这些脂质体纳米颗粒可用作双峰PET/光学成像剂。脂质体靶向恶性肿瘤生长，其双峰特征可用于同步PET和术中成像。
Advances in preclinical molecular imaging have generated new opportunities to noninvasively visualize the biodistribution and tumor targeting of nanoparticle therapeutics. Capitalizing on recent achievements in this area, we sought to develop an 89Zr-based labeling strategy for liposomal nanoparticles that accumulate in tumors via passive targeting mechanisms. 89Zr-labeled liposomes were prepared using 2 different approaches: click labeling and surface chelation. Pharmacokinetic and biodistribution studies, as well as PET/CT imaging of the radiolabeled nanoparticles, were performed on a mouse model of breast cancer. In addition, a dual PET/optical probe was prepared by incorporation of a near-infrared fluorophore and tested in vivo by PET and near-infrared fluorescence imaging. The surface chelation approach proved to be superior in terms of radiochemical yield and stability, as well as in vivo performance. Accumulation of these liposomes in tumor peaked at 24 h after injection and was measured to be 13.7 ± 1.8 percentage injected dose per gram. The in vivo performance of this probe was not essentially perturbed by the incorporation of a near-infrared fluorophore. We have developed a highly modular and efficient strategy for the labeling of liposomal nanoparticles with 89Zr. In xenograft and orthotopic mouse models of breast cancer, we demonstrated that the biodistribution of these nanoparticles can be visualized by PET imaging. In combination with a near-infrared dye, these liposomal nanoparticles can serve as bimodal PET/optical imaging agents. The liposomes target malignant growth, and their bimodal features may be useful for simultaneous PET and intraoperative imaging.