Literature DB >> 33481175

Human Biodistribution and Radiation Dosimetry of the P-Glycoprotein Radiotracer [11C]Metoclopramide.

Martin Bauer1, Sandra Barna2, Matthias Blaickner2,3, Konstantin Prosenz4, Karsten Bamminger5, Verena Pichler5, Nicolas Tournier6, Marcus Hacker5, Markus Zeitlinger4, Georgios Karanikas5, Oliver Langer4,2,5.   

Abstract

PURPOSE: To assess in healthy volunteers the whole-body distribution and dosimetry of [11C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier. PROCEDURES: Ten healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [11C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module.
RESULTS: The majority of the administered dose of [11C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [11C]metoclopramide was 1.69 ± 0.26 μSv/MBq for female subjects and 1.55 ± 0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81 ± 0.23 μGy/MBq and 8.78 ± 0.89 μGy/MBq) and the liver (6.80 ± 0.78 μGy/MBq and 4.91 ± 0.74 μGy/MBq) for female and male subjects, respectively.
CONCLUSIONS: [11C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [11C]metoclopramide was comparable to other 11C-labeled PET tracers.

Entities:  

Keywords:  Biodistribution; Dosimetry; P-glycoprotein; PET; [11C]metoclopramide

Mesh:

Substances:

Year:  2021        PMID: 33481175      PMCID: PMC7910245          DOI: 10.1007/s11307-021-01582-4

Source DB:  PubMed          Journal:  Mol Imaging Biol        ISSN: 1536-1632            Impact factor:   3.484


  21 in total

1.  Blood-brain barrier P-glycoprotein function in Alzheimer's disease.

Authors:  Daniëlle M E van Assema; Mark Lubberink; Martin Bauer; Wiesje M van der Flier; Robert C Schuit; Albert D Windhorst; Emile F I Comans; Nikie J Hoetjes; Nelleke Tolboom; Oliver Langer; Markus Müller; Philip Scheltens; Adriaan A Lammertsma; Bart N M van Berckel
Journal:  Brain       Date:  2011-11-26       Impact factor: 13.501

2.  P-glycoprotein function at the blood-brain barrier in humans can be quantified with the substrate radiotracer 11C-N-desmethyl-loperamide.

Authors:  William C Kreisl; Jeih-San Liow; Nobuyo Kimura; Nicholas Seneca; Sami S Zoghbi; Cheryl L Morse; Peter Herscovitch; Victor W Pike; Robert B Innis
Journal:  J Nucl Med       Date:  2010-03-17       Impact factor: 10.057

3.  Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography.

Authors:  Lucy Sasongko; Jeanne M Link; Mark Muzi; David A Mankoff; Xiaodong Yang; Ann C Collier; Steven C Shoner; Jashvant D Unadkat
Journal:  Clin Pharmacol Ther       Date:  2005-06       Impact factor: 6.875

4.  The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103.

Authors: 
Journal:  Ann ICRP       Date:  2007

Review 5.  Radiation dose estimates for carbon-11-labelled PET tracers.

Authors:  Jasper van der Aart; William A Hallett; Eugenii A Rabiner; Jan Passchier; Robert A Comley
Journal:  Nucl Med Biol       Date:  2011-10-26       Impact factor: 2.408

6.  Identification of novel metoclopramide metabolites in humans: in vitro and in vivo studies.

Authors:  Upendra A Argikar; Javier Gomez; Din Ung; Henry P Parkman; Swati Nagar
Journal:  Drug Metab Dispos       Date:  2010-04-27       Impact factor: 3.922

7.  Imaging P-Glycoprotein Induction at the Blood-Brain Barrier of a β-Amyloidosis Mouse Model with 11C-Metoclopramide PET.

Authors:  Viktoria Zoufal; Severin Mairinger; Mirjam Brackhan; Markus Krohn; Thomas Filip; Michael Sauberer; Johann Stanek; Thomas Wanek; Nicolas Tournier; Martin Bauer; Jens Pahnke; Oliver Langer
Journal:  J Nucl Med       Date:  2019-12-05       Impact factor: 11.082

8.  Activity of P-Glycoprotein, a β-Amyloid Transporter at the Blood-Brain Barrier, Is Compromised in Patients with Mild Alzheimer Disease.

Authors:  Anand K Deo; Soo Borson; Jeanne M Link; Karen Domino; Janet F Eary; Ban Ke; Todd L Richards; David A Mankoff; Satoshi Minoshima; Finbarr O'Sullivan; Sara Eyal; Peng Hsiao; Ken Maravilla; Jashvant D Unadkat
Journal:  J Nucl Med       Date:  2014-05-19       Impact factor: 11.082

9.  IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms.

Authors:  Martin Andersson; Lennart Johansson; Keith Eckerman; Sören Mattsson
Journal:  EJNMMI Res       Date:  2017-11-03       Impact factor: 3.138

10.  Imaging P-Glycoprotein Function at the Blood-Brain Barrier as a Determinant of the Variability in Response to Central Nervous System Drugs.

Authors:  Martin Bauer; Nicolas Tournier; Oliver Langer
Journal:  Clin Pharmacol Ther       Date:  2019-03-23       Impact factor: 6.903

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