Head-to-head comparison of (R)-[C]verapamil and [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)-[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 [F]MC225. This study compares the characteristics of (R)-[C]verapamil and [F]MC225 in the same subjects.

METHODS

Three non-human primates underwent 4 PET scans: 2 with (R)-[C]verapamil and 2 with [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, [F]MC225 V values were higher, and k values were lower than those of (R)-[C]verapamil, whereas K values were not significantly different. After inhibition, V values of the 2 tracers were similar; however, (R)-[C]verapamil K and k values were higher than those of [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 and V of both tracers.

CONCLUSION

[F]MC225 and (R)-[C]verapamil show comparable sensitivity to measure the P-gp function in non-human primates. Moreover, this study highlights the 30-min V as the best parameter to measure decreases in the P-gp function with both tracers. [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.