Test-retest repeatability of [18F]MC225-PET in rodents: A tracer for imaging of P-gp function

Lara Garcia Varela, David Vállez García, Manuel Rodriguez-Pérez, Aren van Waarde, Jurgen Sijbesma, Anna Schildt, Chantal Kwizera, Pablo Aguiar, Tomás Sobrino, Rudi Dierckx, Philip H. Elsinga, Gert Luurtsema*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

In longitudinal PET studies, animals are repeatedly anesthetized which may affect the repeatability of PET measurements. The aim of this study was to assess the effect of anesthesia on the P-gp function as well as the reproducibility of [18F]MC225 PET scans. Thus, dynamic PET scans with blood sampling were conducted in 13 Wistar rats. Seven animals were exposed to isoflurane anesthesia 1 week before the PET scan ("Anesthesia-exposed" PET). A second group of six animals was used to evaluate the reproducibility of measurements of P-gp function at the blood-brain barrier (BBB) with [18F]MC225. In this group, two PET scans were made with a 1 week interval ("Test" and "Retest" PET). Pharmacokinetic parameters were calculated using compartmental models and metabolite-corrected plasma as an input function. "Anesthesia-exposed" animals showed a 28% decrease in whole-brain volume of distribution (VT) (p < 0.001) compared to "Test", where the animals were not previously anesthetized. The VT at "Retest" also decreased (19%) compared to "Test" (p < 0.001). The k2 values in whole-brain were significantly increased by 18% in "Anesthesia-exposed" (p = 0.005) and by 15% in "Retest" (p = 0.008) compared to "Test". However, no significant differences were found in the influx rate constant K1, which is considered as the best parameter to measure the P-gp function. Moreover, Western Blot analysis did not find significant differences in the P-gp expression of animals not pre-exposed to anesthesia ("Test") or pre-exposed animals ("Retest"). To conclude, anesthesia may affect the brain distribution of [18F]MC225 but it does not affect the P-gp expression or function.

Original languageEnglish
Pages (from-to)648-658
Number of pages11
JournalACS Chem Neurosci
Volume11
Issue number4
DOIs
Publication statusPublished - 19-Feb-2020

Keywords

  • BLOOD-BRAIN BARRIER
  • P-GLYCOPROTEIN
  • POSITRON EMISSION TOMOGRAPHY
  • TEST-RETEST RELIABILITY
  • kinetic modelling
  • QUANTIFICATION
  • ABC TRANSPORTER

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