Cargando…

Head-to-head comparison of (R)-[(11)C]verapamil and [(18)F]MC225 in non-human primates, tracers for measuring P-glycoprotein function

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)-[(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...

Descripción completa

Detalles Bibliográficos
Autores principales: García-Varela, Lara, Vállez García, David, Aguiar, Pablo, Kakiuchi, Takeharu, Ohba, Hiroyuki, Harada, Norihiro, Nishiyama, Shingo, Tago, Tetsuro, Elsinga, Philip H., Tsukada, Hideo, Colabufo, Nicola A., Dierckx, Rudi A. J. O., van Waarde, Aren, Toyohara, Jun, Boellaard, Ronald, Luurtsema, Gert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566421/
https://www.ncbi.nlm.nih.gov/pubmed/34117508
http://dx.doi.org/10.1007/s00259-021-05411-2
_version_ 1784594007047798784
author García-Varela, Lara
Vállez García, David
Aguiar, Pablo
Kakiuchi, Takeharu
Ohba, Hiroyuki
Harada, Norihiro
Nishiyama, Shingo
Tago, Tetsuro
Elsinga, Philip H.
Tsukada, Hideo
Colabufo, Nicola A.
Dierckx, Rudi A. J. O.
van Waarde, Aren
Toyohara, Jun
Boellaard, Ronald
Luurtsema, Gert
author_facet García-Varela, Lara
Vállez García, David
Aguiar, Pablo
Kakiuchi, Takeharu
Ohba, Hiroyuki
Harada, Norihiro
Nishiyama, Shingo
Tago, Tetsuro
Elsinga, Philip H.
Tsukada, Hideo
Colabufo, Nicola A.
Dierckx, Rudi A. J. O.
van Waarde, Aren
Toyohara, Jun
Boellaard, Ronald
Luurtsema, Gert
author_sort García-Varela, Lara
collection PubMed
description 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)-[(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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05411-2.
format Online
Article
Text
id pubmed-8566421
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-85664212021-11-15 Head-to-head comparison of (R)-[(11)C]verapamil and [(18)F]MC225 in non-human primates, tracers for measuring P-glycoprotein function García-Varela, Lara Vállez García, David Aguiar, Pablo Kakiuchi, Takeharu Ohba, Hiroyuki Harada, Norihiro Nishiyama, Shingo Tago, Tetsuro Elsinga, Philip H. Tsukada, Hideo Colabufo, Nicola A. Dierckx, Rudi A. J. O. van Waarde, Aren Toyohara, Jun Boellaard, Ronald Luurtsema, Gert Eur J Nucl Med Mol Imaging Original Article 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)-[(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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05411-2. Springer Berlin Heidelberg 2021-06-11 2021 /pmc/articles/PMC8566421/ /pubmed/34117508 http://dx.doi.org/10.1007/s00259-021-05411-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
García-Varela, Lara
Vállez García, David
Aguiar, Pablo
Kakiuchi, Takeharu
Ohba, Hiroyuki
Harada, Norihiro
Nishiyama, Shingo
Tago, Tetsuro
Elsinga, Philip H.
Tsukada, Hideo
Colabufo, Nicola A.
Dierckx, Rudi A. J. O.
van Waarde, Aren
Toyohara, Jun
Boellaard, Ronald
Luurtsema, Gert
Head-to-head comparison of (R)-[(11)C]verapamil and [(18)F]MC225 in non-human primates, tracers for measuring P-glycoprotein function
title Head-to-head comparison of (R)-[(11)C]verapamil and [(18)F]MC225 in non-human primates, tracers for measuring P-glycoprotein function
title_full Head-to-head comparison of (R)-[(11)C]verapamil and [(18)F]MC225 in non-human primates, tracers for measuring P-glycoprotein function
title_fullStr Head-to-head comparison of (R)-[(11)C]verapamil and [(18)F]MC225 in non-human primates, tracers for measuring P-glycoprotein function
title_full_unstemmed Head-to-head comparison of (R)-[(11)C]verapamil and [(18)F]MC225 in non-human primates, tracers for measuring P-glycoprotein function
title_short Head-to-head comparison of (R)-[(11)C]verapamil and [(18)F]MC225 in non-human primates, tracers for measuring P-glycoprotein function
title_sort head-to-head comparison of (r)-[(11)c]verapamil and [(18)f]mc225 in non-human primates, tracers for measuring p-glycoprotein function
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566421/
https://www.ncbi.nlm.nih.gov/pubmed/34117508
http://dx.doi.org/10.1007/s00259-021-05411-2
work_keys_str_mv AT garciavarelalara headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT vallezgarciadavid headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT aguiarpablo headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT kakiuchitakeharu headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT ohbahiroyuki headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT haradanorihiro headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT nishiyamashingo headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT tagotetsuro headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT elsingaphiliph headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT tsukadahideo headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT colabufonicolaa headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT dierckxrudiajo headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT vanwaardearen headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT toyoharajun headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT boellaardronald headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction
AT luurtsemagert headtoheadcomparisonofr11cverapamiland18fmc225innonhumanprimatestracersformeasuringpglycoproteinfunction