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

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.

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces multigenerational alterations in the expression of microRNA in the thymus through epigenetic modifications

“…Because TCDD can cross the placental barrier ( 39 ), the direct effect of TCDD on the thymus in F1 generation can be expected, however, whether the toxic effects can be preserved even in the F2 and subsequent generations remains an intriguing possibility. To that end, several studies have focused on the transgenerational effects of TCDD on the reproductive functions [reviewed in ( 40 , 41 )] and shown that F1 mice exposed to TCDD in utero exhibit reduced fertility and an increased incidence of premature birth, an effect that is maintained for the next three generations ( 42 ). Similarly, female C57BL/6 mice (F1), exposed in utero to TCDD (10 μg/kg) by oral gavage at gestational day (GD) 15 exhibited endometriosis-like uterine phenotype in adult life ( 43 ).…”

Monitoring the hepatobiliary function using image techniques and labeled cholephilic compounds

“…ICG is a hydrophilic tricarbocyanine dye (Figure 1C), which after intravenous injection, rapidly binds to plasma proteins and is secreted by the liver in bile, due to hepatobiliary transporters, such as OATPs [80] and MDR1 (gene ABCB1) (Figure 2) [81]. ICG becomes fluorescent when excited by a flash of light in the near-infrared (NIR) spectrum, which can be detected extracorporeally.…”

Development of a Suite of Gadolinium-Free OATP1-Targeted Paramagnetic Probes for Liver MRI

“…Most recently human OATPs (OATP1B3 and OATP1B1) have been expressed in cancer cells to perform longitudinal, 3D tracking of engineered cells in vivo (Figure ). − …”