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

Yi-Hsueh Lee,Jong-Kai Hsiao,Menq-Rong Wu

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.

Highlights

Molecular imaging, which involves observing molecular events by using a reporter, has facilitated drug development
We conclude that OATP1B1 is a potential reporter for dual magnetic resonance (MR) and NIR fluorescent molecular imaging, especially in conjunction with Gd-BOPTA
MR reporters are specific to a contrast agent; development of new reporters is influenced by the clinical evolution and advancement of these agents

Summary

Introduction

Molecular imaging, which involves observing molecular events by using a reporter, has facilitated drug development. Several magnetic resonance (MR) reporters that transport gadolinium or iron oxide–based nanoparticles have been developed [1,2]. Gadolinium-based contrast agents (GBCAs) are widely used in MRI. The most well-known gadolinium chelates are Gadopentetic acid (Gd-DTPA). Liver-specific contrast agents such as Gd-EOB-DTPA (trade name: Primovist) and Gd-BOTPA (trade name: MultiHance) are two GBCAs commonly used in molecular imaging [5,6]. Reporters that utilize Gd-EOB-DTPA, apical sodiumdependent bile acid cotransporter (ASBT), sodium taurocholate cotransporting polypeptide (NTCP), and organic anion transporting polypeptide (OATP), were studied to determine their efficacy as MR reporters [7,8]. Gd-BOPTA entered clinical use before GdEOB-DTPA, the intracellular uptake mechanism of Gd-BOPTA is unknown, hindering its application in molecular imaging

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