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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 2/2019

Open Access 01-04-2019 | Research Article

Influence of Multidrug Resistance-Associated Proteins on the Excretion of the ABCC1 Imaging Probe 6-Bromo-7-[11C]Methylpurine in Mice

Authors: Viktoria Zoufal, Severin Mairinger, Markus Krohn, Thomas Wanek, Thomas Filip, Michael Sauberer, Johann Stanek, Alexander Traxl, John D. Schuetz, Claudia Kuntner, Jens Pahnke, Oliver Langer

Published in: Molecular Imaging and Biology | Issue 2/2019

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Abstract

Purpose

Multidrug resistance-associated proteins (MRPs) mediate the hepatobiliary and renal excretion of many drugs and drug conjugates. The positron emission tomography (PET) tracer 6-bromo-7-[11C]methylpurine is rapidly converted in tissues by glutathione-S-transferases into its glutathione conjugate, and has been used to measure the activity of Abcc1 in the brain and the lungs of mice. Aim of this work was to investigate if the activity of MRPs in excretory organs can be measured with 6-bromo-7-[11C]methylpurine.

Procedures

We performed PET scans with 6-bromo-7-[11C]methylpurine in groups of wild-type, Abcc4(−/−) and Abcc1(−/−) mice, with and without pre-treatment with the prototypical MRP inhibitor MK571.

Results

6-Bromo-7-[11C]methylpurine-derived radioactivity predominantly underwent renal excretion. In blood, MK571 treatment led to a significant increase in the AUC and a decrease in the elimination rate constant of radioactivity (kelimination,blood). In the kidneys, there were significant decreases in the rate constant for radioactivity uptake from the blood (kuptake,kidney), kelimination,kidney, and the rate constant for tubular secretion of radioactivity (kurine). Experiments in Abcc4(−/−) mice indicated that Abcc4 contributed to renal excretion of 6-bromo-7-[11C]methylpurine-derived radioactivity.

Conclusions

Our data suggest that 6-bromo-7-[11C]methylpurine may be useful to assess the activity of MRPs in the kidneys as well as in other organs (brain, lungs), although further work is needed to identify the MRP subtypes involved in the disposition of 6-bromo-7-[11C]methylpurine-derived radioactivity.
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Metadata
Title
Influence of Multidrug Resistance-Associated Proteins on the Excretion of the ABCC1 Imaging Probe 6-Bromo-7-[11C]Methylpurine in Mice
Authors
Viktoria Zoufal
Severin Mairinger
Markus Krohn
Thomas Wanek
Thomas Filip
Michael Sauberer
Johann Stanek
Alexander Traxl
John D. Schuetz
Claudia Kuntner
Jens Pahnke
Oliver Langer
Publication date
01-04-2019
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 2/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-018-1230-y

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