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European Radiology

, Volume 28, Issue 10, pp 4128–4133 | Cite as

The inhibitory effect of gadoxetate disodium on hepatic transporters: a study using indocyanine green

  • Hiroyuki Akai
  • Koichiro Yasaka
  • Akira Kunimatsu
  • Masanori Nojima
  • Yusuke Inoue
  • Osamu Abe
  • Kuni Ohtomo
  • Shigeru Kiryu
Contrast Media
  • 132 Downloads

Abstract

Objectives

To assess the inhibitory effect of gadoxetate disodium on the transporter system using indocyanine green (ICG).

Materials and Methods

Groups of six female B6 Albino mice were injected with the test agent (0.62 mmol/kg gadoxetate disodium) or phosphate-buffered saline (control) 10 min before injection of ICG. Identical fluorescence images were subsequently obtained to create time-efficiency curves of liver parenchymal uptake. The study was performed on hypothermic and normothermic mice. The logarithms of the absorption rate constants (logKa values) and of the elimination rate constants (logKe values) were calculated for each experimental condition, and between-group differences were compared using Student’s t-test.

Results

The logKe values of the test group were lower than those of the control group at both temperatures (-6.52 vs. -5.87 under hypothermic conditions and -4.54 vs. -4.14 under normothermic conditions), and both differences were statistically significant (p = 0.037, 0.015 respectively). In terms of the logKa values, although the difference did not reach statistical significance (p = 0.052), the test group had lower values than the control group under hypothermic conditions (-0.771 vs. -0.376). In normothermic mice, the logKa values for the test and control groups were 0.037 and 0.277 respectively, thus not significantly different (p = 0.404).

Conclusions

Gadoxetate disodium inhibited ICG excretion. Thus, gadoxetate disodium inhibited the ATP-binding cassette sub-family C member 2 transporter.

Key Points

• Gadoxetate disodium inhibited ICG excretion.

• Gadoxetate disodium tended to inhibit hepatic ICG uptake.

• Drug-drug interactions of gadoxetate disodium need further investigation.

Keywords

Liver Contrast media Indocyanine green Fluorescence Multidrug resistance-associated proteins 

Abbreviations

ABCC

ATP-binding cassette sub-family C member

FLI

Fluorescence imaging

ICG

Indocyanine green

MRI

Magnetic resonance imaging

MRP

Multidrug resistance-associated protein

NTCP

Na+/taurocholate transport protein

OATP

Organic anion-transporting polypeptide

PBS

Phosphate-buffered saline

ROI

Region of interest

Notes

Funding

This study has received funding by Japan Society for the Promotion of Science (JP16K10308).

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Dr. Shigeru Kiryu.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors (Dr. Masanori Nojima) is Master of Public Health and has significant statistical expertise.

Informed consent

Written informed consent was not required for this study because it is an experimental study using mice.

Ethical approval

Approval from the institutional animal care committee was obtained.

Methodology

• experimental

• performed at one institution

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Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  1. 1.Department of Radiology, Institute of Medical ScienceUniversity of TokyoTokyoJapan
  2. 2.Division of Advanced Medicine Promotion, The Advanced Clinical Research Center, Institute of Medical ScienceUniversity of TokyoTokyoJapan
  3. 3.Department of Diagnostic RadiologyKitasato University School of MedicineSagamiharaJapan
  4. 4.Department of Radiology, Graduate School of MedicineUniversity of TokyoTokyoJapan
  5. 5.International University of Health and WelfareTochigiJapan
  6. 6.Department of RadiologyInternational University of Health and Welfare HospitalTochigiJapan

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