Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes
Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes
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铌同位素标记的抗 VEGF 单克隆抗体的缀合、标记和体外/体内评估
DOI：
10.1007/s10967-018-6314-2
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发表时间：
1997
影响因子：
1.6
通讯作者：
F. Rösch
中科院分区：
文献类型：
--
作者：
de la Fuente;V. Radchenko;T. Tsotakos;C. Tsoukalas;M. Paravatou-Petsotas;A. L. Harris;U. Köster;F. Rösch
铌-90（90 Nb）是一种正电子发射放射性核素，其表现出用于设计和合成放射性免疫缀合物的有吸引力的特性。在目前的研究中，我们已经调查了90 Nb作为一个可能的未来同位素免疫PET。在90 Nb体内研究之前，本文描述了使用铌-95（95 Nb）-单克隆抗体类似物的体外和体内研究。95 Nb的半衰期为35天，便于长期研究。评价了95 Nb标记的贝伐单抗用于早期抗血管生成肿瘤反应评估，并将结果与其他成熟的用于免疫PET的PET核素进行了比较。95 Nb定量回收（> 95%）。贝伐单抗用Df-Bz-NCS（Df）螯合物修饰，并用先前分离的95 Nb标记。评价了95 Nb-Df-贝伐单抗在盐水和人血浆中7天内的稳定性，分别呈现> 96%和> 94%的完整产物。对M165荷瘤小鼠进行了生物分布体外研究。在总体积为200 µL的草酸（0.1 M）中获得了高纯度（99.999%）和高放射性浓度（1.7 MBq/µL）的95 Nb，可用于标记。Df-贝伐单抗标记是有效的（> 95%），并且95 Nb-Df-贝伐单抗的体外稳定性是高的。在每只小鼠静脉注射20 μg抗体后，成功地从照射的靶中产生并纯化了95 Nb。以高产率实现了用去铁胺预修饰的贝伐珠单抗的标记。在证明了95 Nb-Df-贝伐单抗的体外稳定性后，体外生物分布研究显示在M165荷瘤小鼠中特异性肿瘤摄取。因此，90 Nb-Df-贝伐单抗和小动物PET的体内研究正在准备中，我们期望90 Nb-Df-缀合抗体将显示用于免疫PET的潜力。
Niobium-90 (90Nb) is a positron emitting radionuclide that exhibits attractive characteristics for use in the design and synthesis of radioimmunoconjugates. In the current study we have investigated90Nb as a possible future isotope forimmuno-PET. Prior to90Nb in vivo studies, this paper describes in vitro andex vivostudies using a Niobium-95 (95Nb)-monoclonal antibody analogue.95Nb has a half-life of 35 days and is convenient for long-term studies.95Nb-labelled bevacizumab was evaluated for early antiangiogenic tumor response assessment and the results were compared with other well established PET nuclides forimmuno-PET.95Nb was quantitatively recovered (> 95%) from irradiated natural Zr in a multistep separation. Bevacizumab was modified with the Df-Bz-NCS (Df) chelate and labelled with previously separated95Nb. Stability of95Nb-Df-bevacizumab was evaluated in saline and in human plasma over 7 days presenting > 96% and > 94% of intact product, respectively. Biodistributionex vivostudies were performed on M165 tumor-bearing mice.95Nb was obtained in high purity (99.999%) and high radioactivity concentration (1.7 MBq/µL) in a total volume of 200 µL oxalic acid (0.1 M), ready for labelling. Df-bevacizumab labelling was efficient (> 95%) and in vitro stability of95Nb-Df-bevacizumab was high.Ex vivostudies displayed good tumor-to-background ratios, optimum after 2 days p.i., after iv injection of 20 µg of antibody per mouse.95Nb was successfully produced and purified from the irradiated target. Labeling of bevacizumab pre-modified with desferrioxamine was achieved in high yields. After in vitro stability of95Nb-Df-bevacizumab was demonstrated,ex vivobiodistribution studies showed specific tumor uptake in M165 tumor-bearing mice. Consequently, in vivo studies with90Nb-Df-bevacizumab and small animal PET are in preparation, and we expect that90Nb-Df-conjugated antibodies will show potential forimmuno-PET.
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影响因子：
3.1
作者：
Radchenko, Valery;Bouziotis, Penelope;Roesch, Frank
通讯作者：
Roesch, Frank
89Zr-PET放射化学在治疗性单克隆抗体和其他生物制品的开发和应用中的应用。
影响因子：
3.4
作者：
D. Vugts;G. Visser;G. V. van Dongen
通讯作者：
G. V. van Dongen
用于正电子发射断层扫描的放射性溴标记示踪剂：可能性和陷阱。
影响因子：
2.3
作者：
V. Tolmachev
通讯作者：
V. Tolmachev
影响因子：
1.8
作者：
Busse, S;Rösch, F;Qaim, SM
通讯作者：
Qaim, SM
从锆靶中分离 90Nb 用于免疫 PET
DOI：
--
发表时间：
2014
期刊：
影响因子：
--
作者：
V. Radchenko;D. Filosofov;O. Bochko;N. Lebedev;A. Rakhimov;H. Hauser;M. Eisenhut;N. Aksenov;G. Bozhikov;B. Ponsard;F. Roesch
通讯作者：
F. Roesch