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

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 [F]MC225 PET scans. Thus, dynamic PET scans with blood sampling were made in 13 Wistar rats. Seven animals were exposed to isoflurane anesthesia one 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 [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 input function. "Anesthesia-exposed" animals showed a 28% decrease in whole-brain volume of distribution (V) (p<0.001) compared to "Test", where the animals were not previously anesthetized. The V at "Retest" also decreased (19%) compared to "Test" (p<0.001). The k 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, 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 no pre-exposed to anesthesia ("Test") or pre-exposed animals ("Retest"). To conclude, anesthesia may affect the brain distribution of [F]MC225 but it does not affect the P-gp expression or function.