The fate of MAb-targeted Cd125mTe/ZnS nanoparticles in vivo
The fate of MAb-targeted Cd125mTe/ZnS nanoparticles in vivo
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DOI：
10.1016/j.nucmedbio.2008.02.001
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发表时间：
2008-05-01
影响因子：
3.1
通讯作者：
Mirzadeh, Saed
中科院分区：
文献类型：
--
作者：
Kennel, Stephen J.;Woodward, Jonathan D.;Mirzadeh, Saed
前言：纳米粒子（NP）具有作为药物和放射性同位素载体的潜力。需要定量测量NP在体内的生物分布以确定这些载体的有效性。我们已经使用了一个模型系统的放射性标记的量子点记录之间的竞争有效的血管靶向和相互作用的NP与网状内皮细胞（RE）system.Methods：我们已经准备了Te-125 m标记的CdTe NP，用ZnS封端。Te-125 m的半衰期和衰变特性与I-125非常相似。合成的微粒在水溶液中稳定，并与巯基乙酸衍生化，然后与特异性抗体缀合。为了评估特异性靶向，我们使用了单克隆抗体MAb 201 B，其结合在肺血管腔中表达的鼠血栓调节蛋白。使用单光子发射计算机断层扫描（SPECT）/计算机断层扫描（CT）成像、组织放射自显影和标准器官生物分布技术测试MAb靶向NP的体内靶向性能。结果：Cd Te-125 m/ZnS NP与MAb 201 B偶联后，在小鼠体内的放射性同位素和抗体活性保持不变，在静脉注射后1 h内在肺内蓄积（>400%注射剂量[ID]/g）。对照抗体偶联的NP在肺中不蓄积（
Introduction: Nanoparticles (NP) have potential as carriers for drugs and radioisotopes. Quantitative measures of NP biodistribution in vivo are needed to determine the effectiveness of these carriers. We have used a model system of radiolabeled quantum dots to document the competition between efficient vascular targeting and interaction of the NP with the reticuloendothelial (RE) system.Methods: We have prepared Te-125m-labeled CdTe NP that are capped with ZnS. Te-125m has a half-life and decay characteristics very similar to those for I-125. The synthesized particles are stable in aqueous solution and are derivatized with mercaptoacetic acid and then conjugated with specific antibody. To evaluate specific targeting, we used the monoclonal antibody MAb 201B that binds to murine thrombomodulin expressed in the lumen of lung blood vessels. The MAb-targeted NP were tested for targeting performance in vivo using single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging, tissue autoradiography and standard organ biodistribution techniques. Biodistribution was also determined in mice that had been depleted of phagocytic cells by use of clodronate-loaded liposomes.Results: Cd Te-125m/ZnS NP coupled with MAb 201B retained radioisotope and antibody activity and accumulated in lung (>400% injected dose [ID]/g) within I h of intravenous injection. Control antibody-coupled NP did not accumulate in lung (