[11c]elacridar as a novel p-glycoprotein pet tracer, assessment of whole-body distribution and...

MEETING ABSTRACT Open Access

[11C]Elacridar as a novel P-glycoprotein PETtracer, assessment of whole-body distribution andradiation dosimetry in humansMartin Bauer1, Markus Zeitlinger1, Georg Dobrozemsky2, Cécile Philippe2, Markus Müller1, Oliver Langer1,3*

From 17th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint meeting with theHungarian Society of Experimental and Clinical Pharmacology (MFT)Innsbruck, Austria. 29-30 September 2011

BackgroundThe ATP-binding cassette transporter P-glycoprotein(P-gp) is expressed at the blood-brain barrier (BBB)where it protects the brain from toxic substances andxenobiotics by active efflux transport. The 11C-labelledthird-generation P-gp inhibitor [11C]elacridar was devel-oped as a positron emission tomography (PET) tracerfor the in vivo quantification of P-gp expression levels indifferent organs. The aim of this study was to providehuman dosimetry estimates for [11C]elacridar based onwhole-body PET.

MethodsWhole-body low dose computed tomography (CT) anddynamic and static whole-body PET scans were acquiredin 4 healthy subjects for a total of 100 min after i.v.injection of 400 ± 8 MBq of [11C]elacridar using a Sie-mens Biograph scanner. Volumes of interest were placedin the brain, liver, pancreas, gallbladder, kidneys, lung,muscle, heart, spleen, bone marrow and bile by usingROVER (v. 2.0.31, ABX, Germany) software. Residencetimes were derived by spreadsheet calculation andadapted to the standard human model. Organ doses andeffective dose were calculated utilizing the OLINDA(v. 1.1, Vanderbilt University) dosimetry program.

ResultsOrgans 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 gall-bladder suggested that >95% of activity was excretedvia the bile. The calculated effective dose was7.0×10−3 mSv/MBq yielding 2.8 mSv for an injectedamount of 400 MBq of [11C]elacridar.

ConclusionsThe estimated radiation burden of [11C]elacridar is inthe range of other 11C-labeled PET tracers and wouldallow multiple PET examinations of the same subjectper year.

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

Author details1Department of Clinical Pharmacology, Division of Clinical Pharmacokineticsand Imaging, Medical University of Vienna, 1090 Vienna, Austria.2Department of Nuclear Medicine, Medical University of Vienna, 1090 Vienna,Austria. 3Health and Environment Department, Molecular Medicine, AITAustrian Institute of Technology GmbH, 2444 Seibersdorf, Austria.

Published: 5 September 2011

doi:10.1186/1471-2210-11-S2-A46Cite this article as: Bauer et al.: [11C]Elacridar as a novel P-glycoproteinPET tracer, assessment of whole-body distribution and radiationdosimetry in humans. BMC Pharmacology 2011 11(Suppl 2):A46.

* Correspondence: oliver.langer@meduniwien.ac.at1Department of Clinical Pharmacology, Division of Clinical Pharmacokineticsand Imaging, Medical University of Vienna, 1090 Vienna, AustriaFull list of author information is available at the end of the article

Bauer et al. BMC Pharmacology 2011, 11(Suppl 2):A46http://www.biomedcentral.com/1471-2210/11/S2/A46

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