Reproducibility of quantitative (R)-[C]verapamil studies
نویسندگان
چکیده
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)-[C] 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)-[C] verapamil data. Methods: Dynamic (R)-[C]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)-[C]verapamil data is a constrained two-tissue compartment model.
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متن کاملThe effect of chronic oral administration of verapamil on learning and retrieval in rats using passive avoidance learning task
Verapamil is a drug that blocks L-type calcium channels and selectively inhibits calcium ion entry into the central and peripheral nervous system cells. Verapamil is used acutely and chronically in treatment of some cardiovascular and central nervous system disorders. It has also been shown that acute administration of verapamil has no significant effect on learning and memory in rats, but the ...
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