Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery
Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery
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DOI：
10.1189/jlb.0206110
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发表时间：
2006-11-01
影响因子：
5.5
通讯作者：
Mosley, R. Lee
中科院分区：
文献类型：
--
作者：
Gorantla, Santhi;Dou, Huanyu;Mosley, R. Lee
我们认为，相同的单核吞噬细胞（MP）[骨髓（BM）和血液单核细胞，组织巨噬细胞，小胶质细胞和树突状细胞]，作为艾滋病毒传播的目标，水库和车辆，可以用作抗逆转录病毒治疗（ART）的车辆。为此，使用BM巨噬细胞（BMM）作为纳米颗粒配制的茚地那韦（NP-IDV）的载体，并通过单光子发射计算机断层扫描（SPECT）、横向相关时间（T-2）* 加权磁共振成像（MRI）、组织学和T-闪烁光谱法监测细胞分布。将用超顺磁性氧化铁和/或（111）铟喹啉标记的BMM静脉内输注到幼稚小鼠中。在最初的7小时内，超过86%的细胞标记被记录在肺内。在第1、3、5和7天，肺中的BMM不到10%，肝脏和脾脏中的BMM分别为74-81%和13-18%。在组织体积的基础上，如通过SPECT和MRI所确定的，脾脏和肝脏中的BMM密度显著大于其他组织。第1天和第7天迁移到淋巴结中的占总BMM的1.5-2%。连续转移负载NP-IDV的BMM在淋巴和非淋巴组织中产生的药物水平在第1天超过报告的治疗浓度200- 350倍，并在第14天保持超过100- 300倍。这些数据显示了巨噬细胞运输的实时动力学和目的地，并证明了监测基于巨噬细胞的纳米制剂ART的可行性。80：1165-1174; 2006.
We posit that the same mononuclear phagocytes (MP) [bone marrow (BM) and blood monocytes, tissue macrophages, microglia, and dendritic cells] which serve as targets, reservoirs, and vehicles for HIV dissemination, can be used as vehicles for antiretroviral therapy (ART). Toward this end, BM macrophages (BMM) were used as carriers for nanoparticle-formulated indinavir (NP-IDV), and the cell distribution was monitored by single photon emission computed tomography (SPECT), transverse relation time (T-2)* weighted magnetic resonance imaging (MRI), histology, and T-scintillation spectrometry. BMM labeled with super paramagnetic iron oxide and/or (111)indium oxine were infused i.v. into naive mice. During the first 7 h, greater than 86% of cell label was recorded within the lungs. On Days 1, 3, 5, and 7, less than 10% of BMM were in lungs, and 74-81% and 13-18% were in liver and spleen, respectively. On a tissue volume basis, as determined by SPECT and MRI, BMM densities in spleen and liver were significantly greater than other tissues. Migration into the lymph nodes on Days I and 7 accounted for 1.5-2% of the total BMM. Adoptive transfer of BMM loaded with NP-IDV produced drug levels in lymphoid and nonlymphoid tissues that exceeded reported therapeutic concentrations by 200- to 350-fold on Day 1 and remained in excess of 100- to 300-fold on Day 14. These data show real-time kinetics and destinations of macrophage trafficking and demonstrate the feasibility of monitoring macrophage-based, nanoformulated ART. J. Leukoc. Biol. 80: 1165-1174; 2006.