Head-to-Head Comparison of C-PBR28 and F-GE180 for Quantification of the Translocator Protein in the Human Brain.

F-GE180 is a third-generation PET tracer for quantifying the translocator protein (TSPO), a biomarker for inflammation. The aim of this study was to perform a head-to-head comparison of F-GE180 and the well-established TSPO tracer C-PBR28 by scanning with both tracers during the same day in the same subjects. Five subjects underwent a 90-min PET scan with C-PBR28 in the morning and F-GE180 in the afternoon. A metabolite-corrected arterial input function was obtained in each subject for both tracers, and the brain uptake was quantified with a 2-tissue-compartment model. The rate of metabolism of F-GE180 in arterial blood was slower than that of C-PBR28 (the percentages of nonmetabolized parent in plasma at 90 min were 74.9% ± 4.15% [mean ± SD] and 11.2% ± 1.90%, respectively). The plasma free fractions were similar for both tracers: 3.5% ± 1.1% for F-GE180 and 4.1% ± 1.1% for C-PBR28. The average total volume of distribution () of F-GE180 was about 20 times smaller than that of C-PBR28 (0.15 ± 0.03 mL/cm for F-GE180 and 3.27 ± 0.66 mL/cm for C-PBR28). F-GE180 was characterized by poor transfer from the vascular compartment to the brain (its plasma-to-tissue rate constant [K] was about 10 times smaller than that of C-PBR28). Moreover, kinetic modeling was more difficult with F-GE180, as its values were identified with a lower precision than those of C-PBR28 and outlying values were more frequent. The of F-GE180 was about 20 times smaller than that of C-PBR28 because of low penetration into the brain from the vascular compartment. In addition, kinetic modeling of F-GE180 was more challenging than that of C-PBR28. Therefore, compared with C-PBR28, F-GE180 had unfavorable characteristics for TSPO imaging of the brain.