In Vitro Assessment of Poly-iodinated Triglyceride Reconstituted Low-Density Lipoprotein: Initial Steps Toward CT Molecular Imaging
In Vitro Assessment of Poly-iodinated Triglyceride Reconstituted Low-Density Lipoprotein: Initial Steps Toward CT Molecular Imaging
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DOI：
10.1016/j.acra.2010.06.006
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发表时间：
2010-11-01
影响因子：
4.8
通讯作者：
Zheng, Gang
中科院分区：
文献类型：
--
作者：
Hill, Melissa L.;Corbin, Ian R.;Zheng, Gang
基本原理和目标：靶向分子探针在使用对比增强计算机断层扫描（CT）的癌症成像中提供了更高特异性的潜力。我们研究了一种低密度脂蛋白（LDL）纳米粒子负载与聚碘化甘油三酯（ITG）的概念研究的证据，有针对性的X射线成像。LDL靶向LDL细胞表面受体（LDLR），其在几种肿瘤类型中过表达。LDL-LDLR途径提出了一个高容量和自我更新的运输系统的分子成像在CT.Materials和方法：ITG的合成和加载到LDL颗粒的核心，形成一个重构的纳米颗粒，以下简称为（rITG）LDL。通过动态光散射测量粒度。用CT成像测量（rITG）LDL溶液的X射线衰减，并针对等效碘浓度校准信号增强。培养的人肝母细胞瘤G2（HepG 2）细胞，过表达LDLR，与（rITG）LDL与或不与天然LDL孵育。结果：用ITG重组LDL是成功的，并没有妥协的颗粒的靶向功能。（rITG）LDL溶液的X射线衰减特性的测量显示有效碘浓度为0.78 mg/mL。体外实验结果表明，（rITG）LDL对HepG 2细胞的CT图像增强作用明显强于对照细胞。结论：（rITG）LDL对HepG 2细胞的CT分子成像具有良好的增强作用。潜在的应用包括乳腺成像和低X射线能量下的小动物成像。需要进行体内实验来验证肿瘤对（rITG）LDL的摄取足以增强检测。在更高的X射线能量下使用，如在常规CT中使用的，将需要进一步增加碘负载。
Rationale and Objectives: Targeted molecular probes offer the potential for greater specificity in cancer imaging with contrast-enhanced computed tomography (CT). We investigate a low-density lipoprotein (LDL) nanoparticle loaded with poly-iodinated triglyceride (ITG) in a proof of concept study of targeted x-ray imaging. LDLs are targeted to the LDL cell surface receptor (LDLR), which is overexpressed in several tumor types. The LDL-LDLR pathway presents a high-capacity and self-renewing transport system for molecular imaging in CT.Materials and Methods: ITG was synthesized and loaded into the core of LDL particles to form a reconstituted nanoparticle, hereafter referred to as (rITG)LDL. Particle size was measured by dynamic light scattering. The x-ray attenuation of the (rITG)LDL solution was measured with CT imaging and signal enhancement was calibrated for equivalent iodine concentration. Cultured human hepatoblastoma G2 (HepG2) cells, which overexpress LDLR, were incubated with (rITG)LDL with or without native LDL. The cells were imaged with CT to characterize particle sequestration.Results: Reconstitution of LDL with ITG was successful and did not compromise the targeting function of the particle. Measurement of the x-ray attenuation properties of the (rITG)LDL solution revealed an effective iodine concentration of 0.78 mg/mL. In vitro studies of HepG2 cells demonstrated a significant increase in CT image intensity over control cells when incubated with (rITG)LDL.Conclusion: The in vitro results of this study suggest that (rITG)LDL can provide adequate image enhancement for CT molecular imaging. Potential applications include breast imaging and small animal imaging at low x-ray energies. In vivo experiments will be required to verify that tumor uptake of (rITG)LDL is sufficient for enhanced detection. Use at higher x-ray energies, as used in conventional CT, will require a further increase in iodine loading.