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使用抗体及抗体相关疗法的诊疗一体化

Theranostics Using Antibodies and Antibody-Related Therapeutics.

作者信息

Moek Kirsten L, Giesen Danique, Kok Iris C, de Groot Derk Jan A, Jalving Mathilde, Fehrmann Rudolf S N, Lub-de Hooge Marjolijn N, Brouwers Adrienne H, de Vries Elisabeth G E

机构信息

Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and.

出版信息

J Nucl Med. 2017 Sep;58(Suppl 2):83S-90S. doi: 10.2967/jnumed.116.186940.

Abstract

In theranostics, radiolabeled compounds are used to determine a treatment strategy by combining therapeutics and diagnostics in the same agent. Monoclonal antibodies (mAbs) and antibody-related therapeutics represent a rapidly expanding group of cancer medicines. Theranostic approaches using these drugs in oncology are particularly interesting because antibodies are designed against specific targets on the tumor cell membrane and immune cells as well as targets in the tumor microenvironment. In addition, these drugs are relatively easy to radiolabel. Noninvasive molecular imaging techniques, such as SPECT and PET, provide information on the whole-body distribution of radiolabeled mAbs and antibody-related therapeutics. Molecular antibody imaging can potentially elucidate drug target expression, tracer uptake in the tumor, tumor saturation, and heterogeneity for these parameters within the tumor. These data can support drug development and may aid in patient stratification and monitoring of the treatment response. Selecting a radionuclide for theranostic purposes generally starts by matching the serum half-life of the mAb or antibody-related therapeutic and the physical half-life of the radionuclide. Furthermore, PET imaging allows better quantification than the SPECT technique. This information has increased interest in theranostics using PET radionuclides with a relatively long physical half-life, such as Zr. In this review, we provide an overview of ongoing research on mAbs and antibody-related theranostics in preclinical and clinical oncologic settings. We identified 24 antibodies or antibody-related therapeutics labeled with PET radionuclides for theranostic purposes in patients. For this approach to become integrated in standard care, further standardization with respect to the procedures involved is required.

摘要

在诊疗一体化中,放射性标记化合物通过将治疗与诊断功能结合于同一试剂来确定治疗策略。单克隆抗体(mAb)及与抗体相关的治疗药物代表了一类迅速发展的癌症药物。在肿瘤学中使用这些药物的诊疗一体化方法尤其引人关注,因为抗体是针对肿瘤细胞膜和免疫细胞上的特定靶点以及肿瘤微环境中的靶点设计的。此外,这些药物相对容易进行放射性标记。非侵入性分子成像技术,如单光子发射计算机断层扫描(SPECT)和正电子发射断层扫描(PET),可提供有关放射性标记单克隆抗体及与抗体相关治疗药物全身分布的信息。分子抗体成像有可能阐明药物靶点表达、示踪剂在肿瘤中的摄取、肿瘤饱和情况以及肿瘤内这些参数的异质性。这些数据可支持药物研发,并有助于患者分层和治疗反应监测。为诊疗一体化目的选择放射性核素通常首先要使单克隆抗体或与抗体相关治疗药物的血清半衰期与放射性核素的物理半衰期相匹配。此外,PET成像比SPECT技术能更好地进行定量分析。这些信息增加了人们对使用物理半衰期相对较长的PET放射性核素(如锆)进行诊疗一体化的兴趣。在本综述中,我们概述了在临床前和临床肿瘤学环境中针对单克隆抗体及与抗体相关诊疗一体化的正在进行的研究。我们确定了24种用于患者诊疗一体化目的的用PET放射性核素标记的抗体或与抗体相关的治疗药物。要使这种方法融入标准治疗,需要对相关程序进行进一步标准化。

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