Labeling and preliminary in vivo assessment of niobium-labeled radioactive species: A proof-of-concept study
Labeling and preliminary in vivo assessment of niobium-labeled radioactive species: A proof-of-concept study
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DOI：
10.1016/j.nucmedbio.2016.02.003
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发表时间：
2016-05-01
影响因子：
3.1
通讯作者：
Roesch, Frank
中科院分区：
文献类型：
--
作者：
Radchenko, Valery;Bouziotis, Penelope;Roesch, Frank
放射性核素标记的生物分子如单克隆抗体或抗体片段用于成像目的的应用被称为免疫闪烁成像。更具体地说，当使用的核素是正电子发射体，如锆-89时，该技术被称为免疫PET。目前，迫切需要具有与所讨论的生物分子的生物动力学良好相关的半衰期并且可以通过稳健的标记化学附着到蛋白质的放射性核素。Nb-90是体内免疫PET的有希望的候选者，这是由于其14.6小时的半衰期和每次衰变的E平均值= 0.35 MeV的低β（+）能量。另一方面，Nb-95由于其半衰期较长（t1/2 = 35天）和生产方便、成本较低（基于反应器的生产），是长期离体生物分布研究的方便替代品。在该原理验证工作中，用Nb-95/90标记单克隆抗体贝伐单抗（Avastin（R）），并在正常Swiss小鼠和荷瘤SCID小鼠中评价体外和体内稳定性。使用Nb-95-贝伐单抗的初始离体实验显示足够的肿瘤摄取，然而同时观察到肝脏、脾脏和肾脏中的高摄取。为了研究这种行为是否是由于 * Nb-贝伐珠单抗的不稳定性或体内其他 *Nb物质的产生，我们对Nb-95-草酸盐、Nb-95-氯化物和Nb-95-Df进行了生物分布研究。除了Nb-95-草酸盐和Nb-95-氯化物的骨蓄积外，这些潜在代谢物物质未显示出任何特异性摄取，有趣的是，这可能作为标记生物分子释放Nb-90的“指示剂”。关于Nb-95-贝伐珠单抗在非肿瘤组织中的初始摄取，较高比活度放射性标记抗体样品的生物分布确实显示在肝脏、脾脏、肾脏或骨骼中的摄取可忽略不计。在实验性小动物PET照相机上获得注射Nb-90-贝伐单抗后的荷瘤SCID小鼠的体内成像，并且确实显示放射性示踪剂在肿瘤区域中的定位。这是第一次，这样的结果在文献中描述，并表明应用Nb-90标记的抗体的免疫PET的目的的承诺。爱思唯尔公司出版
The application of radionuclide-labeled biomolecules such as monoclonal antibodies or antibody fragments for imaging purposes is called immunoscintigraphy. More specifically, when the nuclides used are positron emitters, such as zirconium-89, the technique is referred to as immuno-PET. Currently, there is an urgent need for radionuclides with a half-life which correlates well with the biological kinetics of the biomolecules under question and which can be attached to the proteins by robust labeling chemistry. Nb-90 is a promising candidate for in vivo immuno-PET, due its half-life of 14.6 h and low beta(+) energy of E-mean = 0.35 MeV per decay. Nb-95 on the other hand, is a convenient alternative for longer-term ex vivo biodistribution studies, due to its longer half-life of (t1/2 = 35 days) and its convenient, lower-cost production (reactor-based production). In this proof-of-principle work, the monoclonal antibody bevacizumab (Avastin (R)) was labeled with Nb-95/90 and in vitro and in vivo stability was evaluated in normal Swiss mice and in tumor-bearing SCID mice. Initial ex vivo experiments with Nb-95-bevacizumab showed adequate tumor uptake, however at the same time high uptake in the liver, spleen and kidneys was observed. In order to investigate whether this behavior is due to instability of *Nb-bevacizumab or to the creation of other *Nb species in vivo, we performed biodistribution studies of Nb-95-oxalate, Nb-95-chloride and Nb-95-Df. These potential metabolite species did not show any specific uptake, apart from bone accumulation for Nb-95-oxalate and Nb-95-chloride, which, interestingly, may serve as an "indicator" for the release of Nb-90 from labeled biomolecules. Concerning the initial uptake of Nb-95-bevacizumab in non-tumor tissue, biodistribution of a higher specific activity radiolabeled antibody sample did show only negligible uptake in the liver, spleen, kidneys or bones. In-vivo imaging of a tumor-bearing SCID mouse after injection with Nb-90-bevacizumab was acquired on an experimental small-animal PET camera, and indeed showed localization of the radiotracer in the tumor area. It is the first time that such results are described in the literature, and indicates promise of application of Nb-90-labeled antibodies for the purposes of immuno-PET. Published by Elsevier Inc.