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Labeling and preliminary in vivo assessment of niobium-labeled radioactive species: A proof-of-concept study

机译：铌标记放射性物质的体内评估标记和初探：概念证据研究

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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.
机译：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施用被称为免疫intigraphy。更具体地，当使用的核素是正电子发射器，例如锆-89，该技术被称为免疫宠物。目前，迫切需要具有半衰期的放射性核素，其与所质量的生物分子的生物动力学相关，并且可以通过鲁棒标记化学附着在蛋白质中。 NB-90是体内免疫宠物的有希望的候选者，其半衰期为14.6小时，E-均值的低β（+）能量=每次衰减0.35meV。另一方面，NB-95是一种方便的替代方案，用于长期前体内生物分布研究，由于其较长的半衰期（T1 / 2 = 35天），其方便，较低的生产（基于反应堆生产） ）。在这种原则上的原则上工作中，单克隆抗体贝伐单抗（Avastin）用Nb-95/90标记，体外并体内稳定性在正常的瑞士小鼠中评价和携带肿瘤的Scid小鼠。 NB-95-Bevacizumab的初始exVivo实验显示出足够的肿瘤摄取，但同时肝脏，脾脏和肾的高吸收。为了探讨这种行为是否是由于* Nb-Bevacizumab的不稳定性或在体内创建其他* Nb种类的原因，我们对Nb-95-草酸盐酸酯，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-氯化物的骨积累之外，这些潜在的代谢物物种没有显示出任何特异性摄取，有趣的是，这可以用作来自标记的生物分子的Nb-90的“指示剂”。关于非肿瘤组织中Nb-95-贝伐单抗的初始摄取，较高的特异性活性的生物分布放射性标记抗体样品确实仅显示肝脏，脾脏，肾脏或骨骼中的可忽略不计。在实验小动物宠物摄像机上获得注射NB-90-贝伐单抗后肿瘤的肿瘤SCID小鼠的体内成像，并且确实显示了肿瘤区域的放射机构的定位。这是第一次在文献中描述了这种结果，并表明在免疫宠物目的中施加Nb-90标记的抗体的承诺。 elsevier公司发布

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