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新型多模态分子影像学方法检测鼠胎盘内维生素 H（生物素）转运体的活性。

Novel multimodal molecular imaging of Vitamin H (Biotin) transporter activity in the murine placenta.

机构信息

Department of Biological Regulation, Weizmann Institute of Science, 7610001, Rehovot, Israel.

Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel.

出版信息

Sci Rep. 2020 Nov 27;10(1):20767. doi: 10.1038/s41598-020-77704-9.

DOI:10.1038/s41598-020-77704-9
PMID:33247173
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7695856/
Abstract

Vitamin H (biotin) is delivered to the fetus transplacentally by an active biotin-transport mechanism and is critical for fetal development. Our objective was to develop a comprehensive MRI technique for mapping biotin transporter activity in the murine placenta. Visualization of transporter activity can employ MRI's unique T*-dependent signal 'off-switch', which is triggered by transporter mediated aggregation of biotinylated contrast agent (b-BSA-Gd-DTPA). MRI data were collected from pregnant mice after administration of b-BSA-Gd-DTPA and analyzed using a new sub-voxel biophysical signal model. Validation experiments included competition with native biotin, comparative tests using PET, histology, and ICPMS. MRI signal was governed by binding, aggregation, and clearance of biotin (confirmed by histology). Signal dynamics reflected the placenta's perfusion pattern modulated by biotin transporter activity and trophoblast mediated retention, and were in congruence with a three-compartment sub-voxel model. Pre-saturation of the transporters with free biotin suppressed b-BSA-Gd-DTPA uptake. The results were confirmed by PET, histology and ICPMS. The presented MRI-based platform allows to track activity of essential molecular transporters in the placenta, reflecting a transporter-mediated uptake, followed by retention and aggregation, and recycling associated with the large b-BSA-Gd-DTPA conjugate. The presented DCE-MRI technique can furthermore be used to map and characterize microstructural compartmentation and transporter activity without exposing the fetus to contrast media.

摘要

维生素 H（生物素）通过主动的生物素转运机制传递给胎儿，对胎儿发育至关重要。我们的目标是开发一种全面的 MRI 技术，用于绘制鼠胎盘内生物素转运体活性的图谱。转运体活性的可视化可以利用 MRI 独特的 T*依赖性信号“关闭开关”，该开关由转运体介导的生物素化对比剂（b-BSA-Gd-DTPA）聚集触发。在给予 b-BSA-Gd-DTPA 后，从怀孕的小鼠中收集 MRI 数据，并使用新的亚像素生物物理信号模型进行分析。验证实验包括与天然生物素的竞争、使用 PET、组织学和 ICPMS 的比较测试。MRI 信号由生物素的结合、聚集和清除控制（通过组织学证实）。信号动态反映了胎盘的灌注模式，受生物素转运体活性和滋养层介导的保留的调节，与三腔室亚像素模型一致。用游离生物素预饱和转运体可抑制 b-BSA-Gd-DTPA 的摄取。这些结果得到了 PET、组织学和 ICPMS 的证实。所提出的基于 MRI 的平台允许跟踪胎盘内必需分子转运体的活性，反映出转运体介导的摄取，随后是与大的 b-BSA-Gd-DTPA 缀合物相关的保留和聚集以及再循环。所提出的 DCE-MRI 技术还可用于绘制和表征微结构区室化和转运体活性，而无需使胎儿接触对比剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/a9e2ef4ddb3d/41598_2020_77704_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/214ee67ce2e4/41598_2020_77704_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/94dd0ac11046/41598_2020_77704_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/7a9bc7fb1072/41598_2020_77704_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/59ea4301885d/41598_2020_77704_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/a3950bb9e872/41598_2020_77704_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/cc79256022dd/41598_2020_77704_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/a9e2ef4ddb3d/41598_2020_77704_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/214ee67ce2e4/41598_2020_77704_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/94dd0ac11046/41598_2020_77704_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/7a9bc7fb1072/41598_2020_77704_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/59ea4301885d/41598_2020_77704_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/a3950bb9e872/41598_2020_77704_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/cc79256022dd/41598_2020_77704_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63db/7695856/a9e2ef4ddb3d/41598_2020_77704_Fig7_HTML.jpg

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