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Open Access

[11C]Elacridar as a novel P-glycoprotein PET tracer, assessment of whole-body distribution and radiation dosimetry in humans

  • Martin Bauer1,
  • Markus Zeitlinger1,
  • Georg Dobrozemsky2,
  • Cécile Philippe2,
  • Markus Müller1 and
  • Oliver Langer1, 3Email author
BMC Pharmacology201111(Suppl 2):A46

https://doi.org/10.1186/1471-2210-11-S2-A46

Published: 5 September 2011

Background

The ATP-binding cassette transporter P-glycoprotein (P-gp) is expressed at the blood-brain barrier (BBB) where it protects the brain from toxic substances and xenobiotics by active efflux transport. The 11C-labelled third-generation P-gp inhibitor [11C]elacridar was developed as a positron emission tomography (PET) tracer for the in vivo quantification of P-gp expression levels in different organs. The aim of this study was to provide human dosimetry estimates for [11C]elacridar based on whole-body PET.

Methods

Whole-body low dose computed tomography (CT) and dynamic and static whole-body PET scans were acquired in 4 healthy subjects for a total of 100 min after i.v. injection of 400 ± 8 MBq of [11C]elacridar using a Siemens Biograph scanner. Volumes of interest were placed in the brain, liver, pancreas, gallbladder, kidneys, lung, muscle, heart, spleen, bone marrow and bile by using ROVER (v. 2.0.31, ABX, Germany) software. Residence times were derived by spreadsheet calculation and adapted to the standard human model. Organ doses and effective dose were calculated utilizing the OLINDA (v. 1.1, Vanderbilt University) dosimetry program.

Results

Organs with highest radiation burden included pancreas, spleen, liver and gallbladder wall. Furthermore, lungs, heart wall and kidneys received above average organ doses. As excretory organ the gallbladder was identified. Monoexponential fitting of activity overlying the gallbladder suggested that >95% of activity was excreted via the bile. The calculated effective dose was 7.0×10−3 mSv/MBq yielding 2.8 mSv for an injected amount of 400 MBq of [11C]elacridar.

Conclusions

The estimated radiation burden of [11C]elacridar is in the range of other 11C-labeled PET tracers and would allow multiple PET examinations of the same subject per year.

Declarations

Acknowledgements

The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement number 201380 (Euripides) and from the Austrian Science Fund (FWF) project ‘Transmembrane Transporters in Health and Disease’ (SFB F35).

Authors’ Affiliations

(1)
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics and Imaging, Medical University of Vienna
(2)
Department of Nuclear Medicine, Medical University of Vienna
(3)
Health and Environment Department, Molecular Medicine, AIT Austrian Institute of Technology GmbH

Copyright

© Bauer et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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