Head-to-Head Comparison of 11C-PBR28 and 18F-GE180 for Quantification of the Translocator Protein in the Human Brain

F-18-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-18-GE180 and the well-established TSPO tracer C-11-PBR28 by scanning with both tracers during the same day in the same subjects. Methods: Five subjects underwent a 90-min PET scan with C-11-PBR28 in the morning and F-18-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. Results: The rate of metabolism of F-18-GE180 in arterial blood was slower than that of C-11-PBR28 (the percentages of non-metabolized 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-18-GE180 and 4.1% +/- 1.1% for C-11-PBR28. The average total volume of distribution (VT) of F-18-GE180 was about 20 times smaller than that of C-11-PBR28 (0.15 +/- 0.03 mL/cm(3) for F-18-GE180 and 3.27 +/- 0.66 mL/cm(3) for C-11-PBR28). F-18-GE180 was characterized by poor transfer from the vascular compartment to the brain (its plasma-to-tissue rate constant [K1] was about 10 times smaller than that of C-11-PBR28). Moreover, kinetic modeling was more difficult with F-18-GE180, as its VT values were identified with a lower precision than those of C-11-PBR28 and outlying values were more frequent. Conclusion: The VT of F-18-GE180 was about 20 times smaller than that of C-11-PBR28 because of low penetration into the brain from the vascular compartment. In addition, kinetic modeling of F-18-GE180 was more challenging than that of C-11-PBR28. Therefore, compared with C-11-PBR28, F-18-GE180 had unfavorable characteristics for TSPO imaging of the brain.