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利用亚毫米 PET 成像提高动脉粥样硬化斑块分子标志物的检测能力。

Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging.

机构信息

Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.

Preclinical imaging, MOLECUBES NV, 9000 Ghent, Belgium.

出版信息

Molecules. 2020 Apr 16;25(8):1838. doi: 10.3390/molecules25081838.

DOI:10.3390/molecules25081838
PMID:32316285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7221983/
Abstract

Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET/CT images and ex vivo data showed specific uptake of [F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.

摘要

由于动脉粥样硬化斑块较小且稀疏，因此通过 PET 成像进行非侵入性检测既需要高度特异性的放射性示踪剂，也需要具有高灵敏度和分辨率的成像系统。本研究旨在评估新型氟-18 抗 VCAM-1 纳米抗体（Nb）的靶向性和生物分布，并研究亚毫米分辨率 PET 成像是否可以提高小鼠斑块的检测能力。用新型约束络合试剂（RESCA）螯合剂功能化的抗 VCAM-1 Nb 与 [F]AlF 标记，具有高放射化学产率（>75%）和放射化学纯度（>99%）。随后，将 [F]AlF(RESCA)-cAbVCAM1-5 注射到 ApoE 小鼠中，或与过量未标记的 Nb（对照组）一起注射。使用两种不同的商业可用的 PET/CT 系统以交叉设计顺序对小鼠进行成像，最后进行牺牲以进行离体分析。PET/CT 图像和离体数据均显示 [F]AlF(RESCA)-cAbVCAM1-5 在动脉粥样硬化病变中的特异性摄取。由于体内脱氟作用，还可以注意到非特异性的骨骼摄取。图像分析显示，β-CUBE（MOLECUBES）PET 扫描仪的靶心比和靶脑比更高，表明使用最新的 PET 技术可以改善动脉粥样硬化病变的临床前检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/e112c27dd16e/molecules-25-01838-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/266b59a017c5/molecules-25-01838-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/cc987a1ccbd4/molecules-25-01838-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/fbb6f2e98760/molecules-25-01838-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/e112c27dd16e/molecules-25-01838-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/266b59a017c5/molecules-25-01838-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/cc987a1ccbd4/molecules-25-01838-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/fbb6f2e98760/molecules-25-01838-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92fc/7221983/e112c27dd16e/molecules-25-01838-g004.jpg

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