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

Lara García-Varela, David Vállez García, Pablo Aguiar, Takeharu Kakiuchi, Hiroyuki Ohba, Norihiro Harada, Shingo Nishiyama, Tetsuro Tago, Philip H. Elsinga, Hideo Tsukada, Nicola A. Colabufo, Rudi A. J. O. Dierckx, Aren van Waarde, Jun Toyohara, Ronald Boellaard, Gert Luurtsema

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6 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)4307-4317
Number of pages11
JournalEuropean journal of nuclear medicine and molecular imaging
Issue number13
Early online date2021
Publication statusPublished - Dec 2021


  • Brain imaging
  • Central nervous system
  • Efflux transporter
  • Regional differences

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