Evaluation and application of a novel radioisotope for immuno-PET:Niobium-90

新型免疫PET放射性同位素Niobium-90的评价及应用

• 批准号: 256296058
• 负责人: Professor Dr. Frank Rösch
• 金额: --
• 依托单位: Department Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/256296058?language=en
• 关键词: Evaluation; application; novel; radioisotope; immuno

A yearly increase in tumor cases worldwide stimulated a fast progression of nuclear medicine in the last decades in the diagnosis and treatment of cancer. One attractive example of a novel diagnosis option is immuno-PET: the tracking and quantification of labeled proteins such as monoclonal antibodies (mAb) with positron emission tomography (PET) at high resolution and sensitivity. Common positron emitters as F-18 (T½ = 110 min), O-15 (T½ = 2.04 min), N-13 (T½ = 9.96 min) and C-11 (T½ = 20.4 min) are practically useless for immuno-PET, because the pharmacokinetics and pharmacodynamics of proteins take from several hours to several days and the physical half-lives of these radioisotopes is too short. This fact calls for the development of new radioisotopes with appropriate characteristics (physical half-life, decay mode) to radiolabel proteins.This project aims to evaluate Nb-90 as an isotope for immuno-PET. Its intermediate half-life of 14.6 hours and the high positron branching (53 %) make it appropriate for quantitative in vivo imaging of antibodies and antibody fragments. In previous studies we showed initial strategies for the preparation of Nb-90-labeled antibodies and their high in vitro stability.The aims of this project are:a.) to improve the production method of the radionuclide,b.) to optimize its radiochemical separation, c.) to investigate appropriate labeling protocols, andd.) to label selected monoclonal antibodies.e.) Finally, the in vivo evaluation of Nb-90 labeled biomolecules is planned. We will evaluate the in vivo behavior of full length antibodies as well of antibody fragments. Three well established PET isotopes will be applied as references, Zr-89 (T½ = 78.4 h) for long pharmacokinetic processes and Ga-68 (T1/2 = 67.7 min) and Sc-44 (T1/2 = 3.92 h) for antibody fragments. To attach the isotopes to biomolecules, the same bifunctional chelator desferrioxamine is considered as the ligand of choice.

在过去的几十年里，全球肿瘤病例的逐年增加刺激了核医学在癌症诊断和治疗方面的快速发展。一个有吸引力的新的诊断选择的例子是免疫PET：跟踪和定量标记的蛋白质，如单克隆抗体（mAb）与正电子发射断层扫描（PET）在高分辨率和灵敏度。常见的正电子发射体如F-18（T1/2 = 110 min）、O-15（T1/2 = 2.04 min）、N-13（T1/2 = 9.96 min）和C-11（T1/2 = 20.4 min）对于免疫PET实际上是无用的，因为蛋白质的药代动力学和药效学需要几个小时到几天，并且这些放射性同位素的物理半衰期太短。这一事实要求开发具有适当特性（物理半衰期，衰变模式）的新放射性同位素来放射性标记蛋白质。本项目旨在评估Nb-90作为免疫PET同位素的价值。其14.6小时的中间半衰期和高正电子分支（53%）使其适合于抗体和抗体片段的定量体内成像。在先前的研究中，我们展示了制备Nb-90标记的抗体及其高体外稳定性的初步策略。 改进放射性核素的生产方法，B.） 以优化其放射化学分离，c.） 研究适当的标签方案，和d.） 以标记选择的单克隆抗体。 最后，在体内评价Nb-90标记的生物分子的计划。我们将评估全长抗体以及抗体片段的体内行为。将应用三种良好建立的PET同位素作为参考，Zr-89（T1/2 = 78.4 h）用于长药代动力学过程，Ga-68（T1/2 = 67.7 min）和Sc-44（T1/2 = 3.92 h）用于抗体片段。为了将同位素连接到生物分子上，相同的双功能螯合剂去铁胺被认为是选择的配体。

项目成果

Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes

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
• 发表时间: 1997
• 期刊: Journal of Radioanalytical and Nuclear Chemistry
• 影响因子: 1.6
• 作者: de la Fuente;V. Radchenko;T. Tsotakos;C. Tsoukalas;M. Paravatou-Petsotas;A. L. Harris;U. Köster;F. Rösch
• 通讯作者: F. Rösch

Direct flow separation strategy, to isolate no-carrier-added 90Nb from irradiated Mo or Zr targets

• DOI: 10.1515/ract-2015-2543
• 发表时间: 2016-09
• 期刊: Radiochimica Acta
• 影响因子: 1.8
• 作者: V. Radchenko;D. Filosofov;J. Dadakhanov;D. Karaivanov;A. Marinova;A. Baimukhanova;F. Roesch