4.7 Article

In vivo imaging of alpha-synuclein with antibody-based PET

期刊

NEUROPHARMACOLOGY
卷 208, 期 -, 页码 -

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2022.108985

关键词

Positron emission tomography; Alpha-synuclein; Antibody radioligand; Neurodegeneration; Transgenic mice; L61

资金

  1. Knut and Alice Wallenberg Foundation
  2. Swedish research council [2017-02413, 2018-02715]
  3. Alzheimerfonden
  4. Ahlenstiftelsen
  5. Parkinsonfonden
  6. Torsten Soderbergs stiftelse
  7. Hjarnfonden
  8. Konung Gustaf V:S och Drottning Victorias frimurarestiftelse
  9. Major Gosta Linds Minnesfond
  10. Norheds stiftelse
  11. Tore Nilssons stiftelse
  12. O.E. och Edla Johanssons stiftelse
  13. Magnus Bergvalls stiftelse
  14. European Union [813528]
  15. Swedish Research Council [2018-02715, 2017-02413] Funding Source: Swedish Research Council

向作者/读者索取更多资源

By utilizing bispecific antibodies for PET imaging, alpha SYN was successfully visualized in the mouse brain, showing potential application in synucleinopathies. However, challenges remain in imaging intracellular alpha SYN inclusions.
The protein alpha-synuclein (alpha SYN) plays a central role in synucleinopathies such as Parkinsons's disease (PD) and multiple system atrophy (MSA). Presently, there are no selective alpha SYN positron emission tomography (PET) radioligands that do not also show affinity to amyloid-beta (A beta). We have previously shown that radiolabeled antibodies, engineered to enter the brain via the transferrin receptor (TfR), is a promising approach for PET imaging of intrabrain targets. In this study, we used this strategy to visualize alpha SYN in the living mouse brain. Five bispecific antibodies, binding to both the murine TfR and alpha SYN were generated and radiolabeled with iodine-125 or iodine-124. All bispecific antibodies bound to alpha SYN and mTfR before and after radiolabelling in an ELISA assay, and bound to brain sections prepared from alpha SYN overexpressing mice as well as human PD- and MSA subjects, but not control tissues in autoradiography. Brain concentrations of the bispecific antibodies were be-tween 26 and 63 times higher than the unmodified IgG format 2 h post-injection, corresponding to about 1.5% of the injected dose per gram brain tissue. Additionally, intrastriatal alpha SYN fibrils were visualized with PET in an alpha SYN deposition mouse model with one of the bispecific antibodies, [I-124]RmAbSynO2-scFv8D3. However, PET images acquired in alpha SYN transgenic mice with verified brain pathology injected with [I-124]RmAbSynO2-scFv8D3 and [I-124]RmAb48-scFv8D3 showed no increase in antibody retention compared to WT mice. Despite successful imaging of deposited extracellular alpha SYN using a brain-penetrating antibody-based radioligand with no cross-specificity towards A beta, this proof-of-concept study demonstrates challenges in imaging intracellular alpha SYN inclusions present in synucleinopathies.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据