Inbal E. Bilton

Weizmann Institute of Science

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Tolulope A. Aweda

GlaxoSmithKline (Netherlands)

Jennifer L. Bartels

University of Alabama at Birmingham

Noam Ben‐Eliezer

Tel Aviv University

Solana Fernandez

University of Alabama at Birmingham

Nicholas A. Clanton

The University of Texas at San Antonio

Suzanne E. Lapi

University of Alabama at Birmingham

Joel R. Garbow

Mallinckrodt (United States)

Michal Neeman

Weizmann Institute of Science

Rebecca Beacham

University of Alabama at Birmingham

Marina Lysenko

Weizmann Institute of Science

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University of Alabama at Birmingham

Mallinckrodt (United States)

Washington University in St. Louis

Weizmann Institute of Science

University of Alabama

University of California, Los Angeles

Birmingham VA Medical Center

Advanced Imaging Research (United States)

GlaxoSmithKline (Netherlands)

University of California, Davis

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

Scientific Reports (2020)

Noam Ben‐Eliezer Marina Lysenko Inbal E. Bilton Ofra Golani Jennifer L. Bartels

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 2 *-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.

10.1038/s41598-020-77704-9

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

Scientific Reports (2021)

Noam Ben‐Eliezer Marina Lysenko Inbal E. Bilton Ofra Golani Jennifer L. Bartels

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

10.1038/s41598-021-85422-z

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