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奥格尔:精准医学的未来。

Auger: The future of precision medicine.

机构信息

Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA.

出版信息

Nucl Med Biol. 2021 May-Jun;96-97:50-53. doi: 10.1016/j.nucmedbio.2021.03.002. Epub 2021 Mar 19.

Abstract

First reported by Lise Meitner in 1922 and independently by Pierre Auger in 1923, the Auger effect has been explored as a potential source for targeted radiotherapy. The Auger effect is based on the emission of a low energy electron (typically <25 keV) from an atom post electron capture (EC), internal conversion (IC), or incident X-rays excitation. This phenomenon can cause the emission of a primary electron and multiple electron tracks typically in the nearest proximity of the emission site (2-500 nm). The short range of the emitted Auger cascade results in medium/high levels of linear energy transfer (4-26 keV/μm) exerted on the surrounding tissue. This property makes Auger emitters the ideal candidates for delivering high levels of targeted radiation to a specific target with dimensions comparable to, for example, the DNA. By using a targeting vector such as a small molecule, peptide or antibody, one has the potential of delivering high levels of radiation to tumor specific biomarkers while circumventing off-site toxicity in healthy cells; a challenge which is harder to overcome when using other, longer range sources of radiation such as beta and alpha emitting radionuclides. Several reviews on Auger emitters have been published over the years with two recent examples. For these reviews and others, we support their analysis and therefore to avoid simple repetition, this commentary will seek to address additional aspects and viewpoints. Specifically, we will focus on those most promising preclinical and clinical studies using small molecules, peptides, antibodies and how these studies may serve as a template for future studies.

摘要

1922 年由莉泽·迈特纳首次报道,1923 年皮埃尔·奥格独立报道,俄歇效应已被探索作为靶向放射治疗的潜在来源。俄歇效应基于电子俘获(EC)、内转换(IC)或入射 X 射线激发后原子发射的低能电子(通常 <25keV)。这种现象会导致发射一个初级电子和多个电子轨迹,通常在发射点的最近邻(2-500nm)。发射的俄歇级联的短程导致周围组织中中等/高水平的线性能量转移(4-26keV/μm)。这种特性使俄歇发射器成为将高剂量的靶向辐射递送到与 DNA 尺寸相当的特定靶标的理想候选物。通过使用靶向载体,如小分子、肽或抗体,人们有可能将高水平的辐射递送到肿瘤特异性生物标志物,同时避免健康细胞的脱靶毒性;当使用β和α发射放射性核素等其他长程辐射源时,这是一个更难克服的挑战。多年来已经发表了几篇关于俄歇发射器的综述,最近有两个例子。对于这些综述和其他综述,我们支持他们的分析,因此为了避免简单重复,本评论将寻求解决其他方面和观点。具体来说,我们将重点关注那些使用小分子、肽、抗体的最有前途的临床前和临床研究,以及这些研究如何为未来的研究提供模板。

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