Organic anion-transporting polypeptide 1B3 as a dual reporter gene for fluorescence and magnetic resonance imaging

FASEB J. 2018 Mar;32(3):1705-1715. doi: 10.1096/fj.201700767R. Epub 2018 Jan 3.

Abstract

Reporter proteins have broad applications in visualizing molecular events at the cellular, tissue and whole-body levels. Transmembrane transporters recognizing specific molecular domains are of particular interest because they enable the migration of signal-source molecules from the extracellular space to the cytoplasm for subsequent application in multimodality imaging. Organic anion-transporting polypeptides (OATPs) have demonstrated their MRI reporter efficacy. We further expanded their use as a dual-modality reporter in MRI and noninvasive in vivo imaging system (IVIS). We overexpressed OATP1B3 in the HT-1080 sarcoma cell line. Both Gd-EOB-DTPA, an MRI contrast agent, and indocyanine green (ICG), a near-infrared fluorescent dye that provides better deep-tissue detection because of its long wavelength, could be delivered to the intracellular space and imaged in a tumor-bearing nude mouse model. Our in vivo dual-imaging reporter system achieved high sensitivity in MRI and observation periods lasting as long as 96 h in IVIS. Because of the superior temporal and spatial resolutions and the clinical availability of both ICG and Gd-EOB-DTPA, this dual-imaging OATP1B3 system will find biomedical use in tumor biology, stem cell trafficking, and tissue engineering.-Wu, M.-R., Liu, H.-M., Lu, C.-W., Shen, W.-H., Lin, I.-J., Liao, L.-W., Huang, Y.-Y., Shieh, M.-J., Hsiao, J.-K. Organic anion-transporting polypeptide 1B3 as a dual reporter gene for fluorescence and magnetic resonance imaging.

Keywords: Gd-EOB-DTPA; ICG; IVIS; cell tracking; near-infrared.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Genes, Reporter*
  • Heterografts
  • Humans
  • Liver-Specific Organic Anion Transporter 1 / genetics
  • Liver-Specific Organic Anion Transporter 1 / metabolism*
  • Magnetic Resonance Imaging*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Optical Imaging
  • Sarcoma* / diagnostic imaging
  • Sarcoma* / genetics
  • Sarcoma* / metabolism

Substances

  • Liver-Specific Organic Anion Transporter 1
  • SLCO1B1 protein, human