Head-to-head comparison of (R)-[11C]verapamil and [18F]MC225 in non-human primates, tracers for measuring P-glycoprotein function.
Eur J Nucl Med Mol Imaging
; 48(13): 4307-4317, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34117508
ABSTRACT
PURPOSE:
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)-[11C]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 [18F]MC225. This study compares the characteristics of (R)-[11C]verapamil and [18F]MC225 in the same subjects.METHODS:
Three non-human primates underwent 4 PET scans 2 with (R)-[11C]verapamil and 2 with [18F]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, [18F]MC225 VT values were higher, and k2 values were lower than those of (R)-[11C]verapamil, whereas K1 values were not significantly different. After inhibition, VT values of the 2 tracers were similar; however, (R)-[11C]verapamil K1 and k2 values were higher than those of [18F]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 K1 and VT of both tracers.CONCLUSION:
[18F]MC225 and (R)-[11C]verapamil show comparable sensitivity to measure the P-gp function in non-human primates. Moreover, this study highlights the 30-min VT as the best parameter to measure decreases in the P-gp function with both tracers. [18F]MC225 may become the first radiofluorinated tracer able to measure decreases and increases in the P-gp function due to its higher baseline VT.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
/
Verapamil
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Nucl Med Mol Imaging
Assunto da revista:
MEDICINA NUCLEAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda