Organic Anion Transporting Polypeptide 1B1 Is a Potential Reporter for Dual MR and Optical Imaging

Int J Mol Sci. 2021 Aug 16;22(16):8797. doi: 10.3390/ijms22168797.

Abstract

Membrane proteins responsible for transporting magnetic resonance (MR) and fluorescent contrast agents are of particular importance because they are potential reporter proteins in noninvasive molecular imaging. Gadobenate dimeglumine (Gd-BOPTA), a liver-specific MR contrast agent, has been used globally for more than 10 years. However, the corresponding molecular transportation mechanism has not been validated. We previously reported that the organic anion transporting polypeptide (OATP) 1B3 has an uptake capability for both MR agents (Gd-EOB-DTPA) and indocyanine green (ICG), a clinically available near-infrared (NIR) fluorescent dye. This study further evaluated OATP1B1, another polypeptide of the OATP family, to determine its reporter capability. In the OATP1B1 transfected 293T transient expression model, both Gd-BOPTA and Gd-EOB-DTPA uptake were confirmed through 1.5 T MR imaging. In the constant OAPT1B1 and OATP1B3 expression model in the HT-1080 cell line, both HT-1080-OAPT1B1 and HT-1080-OATP1B3 were observed to ingest Gd-BOPTA and Gd-EOB-DTPA. Lastly, we validated the ICG uptake capability of both OATP1B1 and OATP1B3. OAPT1B3 exhibited a superior ICG uptake capability to that of OAPT1B1. We conclude that OATP1B1 is a potential reporter for dual MR and NIR fluorescent molecular imaging, especially in conjunction with Gd-BOPTA.

Keywords: Gd-BOTPA; indocyanine green; near-infrared; organic anion transporting polypeptide; reporter gene.

MeSH terms

  • Gadolinium DTPA / chemistry*
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Liver-Specific Organic Anion Transporter 1 / chemistry
  • Liver-Specific Organic Anion Transporter 1 / genetics
  • Liver-Specific Organic Anion Transporter 1 / metabolism*
  • Magnetic Resonance Imaging
  • Meglumine / analogs & derivatives*
  • Meglumine / chemistry
  • Molecular Imaging
  • Optical Imaging / methods*
  • Organometallic Compounds / chemistry*
  • Solute Carrier Organic Anion Transporter Family Member 1B3 / chemistry
  • Solute Carrier Organic Anion Transporter Family Member 1B3 / genetics
  • Solute Carrier Organic Anion Transporter Family Member 1B3 / metabolism

Substances

  • Liver-Specific Organic Anion Transporter 1
  • Organometallic Compounds
  • SLCO1B1 protein, human
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • gadolinium ethoxybenzyl DTPA
  • gadobenic acid
  • Meglumine
  • Gadolinium DTPA