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基于CD11b的预靶向单光子发射计算机断层显像/计算机断层扫描成像可检测主动脉瘤中的炎症。

CD11b-Based Pre-Targeted SPECT/CT Imaging Allows for the Detection of Inflammation in Aortic Aneurysm.

作者信息

Zhou Xiaonan, Zhu Kai, Zhang Yiqiu, Ming Yang, Shi Dai, Tan Hui, Xiang Bitao, Zhu Shichao, Cheng Dengfeng, Lai Hao, Wang Chunsheng, Liu Guobing

机构信息

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, People's Republic of China.

出版信息

J Inflamm Res. 2022 Mar 16;15:1921-1933. doi: 10.2147/JIR.S350593. eCollection 2022.

DOI:10.2147/JIR.S350593
PMID:35321320
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8935951/
Abstract

PURPOSE

To investigate the feasibility of a pre-targeted imaging strategy based on the cycloaddition between 1,2,4,5-terazine (Tz) and trans-cyclooctene (TCO) for evaluating CD11b expression in inflammatory aortic aneurysm (AA) using single photon emission computed tomography/computed tomography (SPECT/CT).

METHODS

C57BL/6J mice were fed β-aminopropionitrile (1 g/kg/day) for 4 weeks to establish AA models. Anti-CD11b-TCO was synthesized and Tc-HYNIC-PEG-Tz was designed for pre-targeted SPECT/CT. The affinity and specificity of the probe for the inflammatory cell line Raw-264.7 were investigated. Then, anti-CD11b-TCO pre-targeted and Tc-HYNIC-PEG-Tz based SPECT/CT were performed to detect in vivo inflammation in AA. Finally, ex vivo aortic breast-specific gamma imaging (BSGI), Western blot assays, and immunohistochemical CD11b staining were performed to confirm the in vivo findings of SPECT/CT.

RESULTS

In the AA models, 65.22% (15/23) had aortic lesions, including 43.48% (10/23) AA lesions. The anti-CD11b-TCO presented with a high TCO coupling ratio (7.43), and the Tc-HYNIC-PEG-Tz showed high radio-purity (>95%), good in vitro stability and a rapid clearance rate. Additionally, anti-CD11b-TCO and Tc-HYNIC-PEG-Tz presented high click rate (~89%). The in vitro clicked compound, Tc-HYNIC-PEG-Tz/TCO-anti-CD11b, showed high affinity and specificity for Raw-264.7 cells. Tc-HYNIC-PEG-Tz/TCO-anti-CD11b pre-targeting SPECT/CT successfully demonstrated inflammatory AA with a high AA-to-background ratio in AA mice, compared to AA mice that were injected with Tc-HYNIC-Tz/TCO-IgG (8.13 versus 3.71, < 0.001) and control mice injected with Tc-HYNIC-Tz/TCO-anti-CD11b (8.13 versus 3.66, < 0.001). This result was confirmed by ex vivo BSGI performed immediately after SPECT/CT and immunohistochemical CD11b staining.

CONCLUSION

SPECT/CT imaging using the anti-CD11b-TCO/Tz-PEG-HYNIC-Tc based pre-targeting imaging strategy allows for the detection of inflammation in progressive AA.

摘要

目的

研究基于1,2,4,5 - 四嗪（Tz）与反式环辛烯（TCO）之间的环加成反应的预靶向成像策略，用于通过单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）评估炎性主动脉瘤（AA）中CD11b的表达。

方法

给C57BL/6J小鼠喂食β-氨基丙腈（1 g/kg/天）4周以建立AA模型。合成抗CD11b - TCO，并设计Tc - HYNIC - PEG - Tz用于预靶向SPECT/CT。研究该探针对炎性细胞系Raw - 264.7的亲和力和特异性。然后，进行抗CD11b - TCO预靶向和基于Tc - HYNIC - PEG - Tz的SPECT/CT以检测AA中的体内炎症。最后，进行离体主动脉乳腺特异性伽马成像（BSGI）、蛋白质印迹分析和免疫组织化学CD11b染色以确认SPECT/CT的体内结果。

结果

在AA模型中，65.22%（15/23）有主动脉病变，其中43.48%（10/23）为AA病变。抗CD11b - TCO呈现高TCO偶联率（7.43），且Tc - HYNIC - PEG - Tz显示出高放射纯度（>95%）、良好的体外稳定性和快速清除率。此外，抗CD11b - TCO和Tc - HYNIC - PEG - Tz呈现高点击率（~89%）。体外点击化合物Tc - HYNIC - PEG - Tz/TCO - 抗CD11b对Raw - 264.7细胞显示出高亲和力和特异性。与注射Tc - HYNIC - Tz/TCO - IgG的AA小鼠（8.13对3.71，<0.001）和注射Tc - HYNIC - Tz/TCO - 抗CD11b的对照小鼠（8.13对3.66，<0.001）相比，Tc - HYNIC - PEG - Tz/TCO - 抗CD11b预靶向SPECT/CT成功地在AA小鼠中显示出具有高AA与背景比值的炎性AA。SPECT/CT后立即进行的离体BSGI和免疫组织化学CD11b染色证实了这一结果。

结论

使用基于抗CD11b - TCO/Tz - PEG - HYNIC - Tc的预靶向成像策略的SPECT/CT成像能够检测进展性AA中的炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/7490921edb01/JIR-15-1921-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/fca6b7cdd7c5/JIR-15-1921-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/20f7ec646547/JIR-15-1921-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/7490921edb01/JIR-15-1921-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/1f6be8730f51/JIR-15-1921-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/b49c065b9884/JIR-15-1921-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/f52546b29e2d/JIR-15-1921-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/d73c05861326/JIR-15-1921-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/fca6b7cdd7c5/JIR-15-1921-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/20f7ec646547/JIR-15-1921-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7904/8935951/7490921edb01/JIR-15-1921-g0007.jpg

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