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Reproducibility of quantitative (R)-[11C]verapamil studies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
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2012 (English)In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 2, 1Article in journal (Refereed) Published
Abstract [en]

Background

P-glycoprotein [Pgp] dysfunction may be involved in neurodegenerative diseases, such as Alzheimer's disease, and in drug resistant epilepsy. Positron emission tomography using the Pgp substrate tracer (R)-[11C]verapamil enables in vivo quantification of Pgp function at the human blood-brain barrier. Knowledge of test-retest variability is important for assessing changes over time or after treatment with disease-modifying drugs. The purpose of this study was to assess reproducibility of several tracer kinetic models used for analysis of (R)-[11C]verapamil data.

Methods

Dynamic (R)-[11C]verapamil scans with arterial sampling were performed twice on the same day in 13 healthy controls. Data were reconstructed using both filtered back projection [FBP] and partial volume corrected ordered subset expectation maximization [PVC OSEM]. All data were analysed using single-tissue and two-tissue compartment models. Global and regional test-retest variability was determined for various outcome measures.

Results

Analysis using the Akaike information criterion showed that a constrained two-tissue compartment model provided the best fits to the data. Global test-retest variability of the volume of distribution was comparable for single-tissue (6%) and constrained two-tissue (9%) compartment models. Using a single-tissue compartment model covering the first 10 min of data yielded acceptable global test-retest variability (9%) for the outcome measure K1. Test-retest variability of binding potential derived from the constrained two-tissue compartment model was less robust, but still acceptable (22%). Test-retest variability was comparable for PVC OSEM and FBP reconstructed data.

Conclusion

The model of choice for analysing (R)-[11C]verapamil data is a constrained two-tissue compartment model.

Place, publisher, year, edition, pages
2012. Vol. 2, 1
Keyword [en]
Positron emission tomography, P-glycoprotein, reproducibility, (R)-[C-11]verapamil
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-189066DOI: 10.1186/2191-219X-2-1ISI: 000209435700001PubMedID: 22251281OAI: oai:DiVA.org:uu-189066DiVA: diva2:580594
Funder
EU, FP7, Seventh Framework Programme, 201380
Available from: 2012-12-23 Created: 2012-12-23 Last updated: 2017-12-06Bibliographically approved

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Lubberink, Mark

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