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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 [ 18 F]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 [ 18 F]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 ( V  T ) ( p &lt; 0.001) compared to "Test", where the animals were not previously anesthetized. The V  T at "Retest" also decreased (19%) compared to "Test" ( p &lt; 0.001). The k  2 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 K  1 , 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 [ 18 F]MC225 but it does not affect the P-gp expression or function.

Test–Retest Repeatability of [18F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

Test–Retest Repeatability of [¹⁸F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function