In:
European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 48, No. 13 ( 2021-12), p. 4307-4317
Abstract:
P-glycoprotein (P-gp) function is altered in several brain disorders; thus, it is of interest to monitor the P-gp function in vivo using PET. ( R )-[ 11 C]verapamil is considered the gold standard tracer to measure the P-gp function; however, it presents some drawbacks that limit its use. New P-gp tracers have been developed with improved properties, such as [ 18 F]MC225. This study compares the characteristics of ( R )-[ 11 C]verapamil and [ 18 F]MC225 in the same subjects. Methods Three non-human primates underwent 4 PET scans: 2 with ( R )-[ 11 C]verapamil and 2 with [ 18 F]MC225, at baseline and after P-gp inhibition. The 30-min PET data were analyzed using 1-Tissue Compartment Model (1-TCM) and metabolite-corrected plasma as input function. Tracer kinetic parameters at baseline and after inhibition were compared. Regional differences and simplified methods to quantify the P-gp function were also assessed. Results At baseline, [ 18 F]MC225 V T values were higher, and k 2 values were lower than those of ( R )-[ 11 C]verapamil, whereas K 1 values were not significantly different. After inhibition, V T values of the 2 tracers were similar; however, ( R )-[ 11 C]verapamil K 1 and k 2 values were higher than those of [ 18 F]MC225. Significant regional differences between tracers were found at baseline, which disappeared after inhibition. The positive slope of the SUV-TAC was positively correlated to the K 1 and V T of both tracers. Conclusion [ 18 F]MC225 and ( R )-[ 11 C]verapamil show comparable sensitivity to measure the P-gp function in non-human primates. Moreover, this study highlights the 30-min V T as the best parameter to measure decreases in the P-gp function with both tracers. [ 18 F]MC225 may become the first radiofluorinated tracer able to measure decreases and increases in the P-gp function due to its higher baseline V T .
Type of Medium:
Online Resource
ISSN:
1619-7070
,
1619-7089
DOI:
10.1007/s00259-021-05411-2
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2098375-X
