Novel multimodal molecular imaging of Vitamin H (Biotin) transporter activity in the murine placenta
| Autor: | Michal Neeman, Tolulope A. Aweda, Suzanne E. Lapi, Jennifer L. Bartels, Inbal E Bilton, Marina Lysenko, Joel R. Garbow, Rebecca Beacham, Nicholas A Clanton, Noam Ben-Eliezer, Ofra Golani, Solana Fernandez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Embryology Biotin transporter activity Reproductive biology Molecular imaging Article Fluorescence imaging Imaging 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Magnetic resonance imaging Biotin Placenta medicine Fetus Multidisciplinary Chemistry Trophoblast Transporter Molecular biophysics Cell biology 030104 developmental biology medicine.anatomical_structure Preclinical research Biotinylation Permeation and transport Positron-emission tomography Biomedical engineering 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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 T2*-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|