Comparison of [18F]FEPPA and [11C]PBR28, novel peripheral benzodiazepine receptor ligands for PET, in a rat model of neuroinflammation

Objectives Recently, several novel peripheral benzodiazepine receptor (PBR) ligands which have much higher brain uptake and specific binding than [¹¹C]PK11195 have been developed. We compared two such ligands, [¹⁸F]N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide (FEPPA) and N-acetyl-N-(2-[¹¹C]methoxybenzyl)-2-phenoxy-5-pyridimine (PBR28), in a rat model of neuroinflammation.

Methods Ten μg of 6-OHDA was injected into the rat right(R) striatum (ST). On day 4, two dynamic PET scans were performed each with an animal PET scanner after an injection of PBR28 and then FEPPA (n=10). Following immunostaining was performed for confirmation of activated microglia. Regions of interest were placed over the ST bilaterally on slices of both PBR28 and FEPPA PET images. Averaged time activity curves (TACs) and R/left(L)ST uptake ratios for PBR28 and FEPPA (20-55min) were compared between the two ligands.

Results TACs showed rapid entry of both ligands in both ST. R ST showed slower clearance of the both ligands than L ST. This receptor binding mediated slow clearance was superior for FEPPA resulting in better S/N of the images. The R/L ST uptake ratios in FEPPA rats (1.22 ± 0.12) were higher than in PBR28 rats (1.14 ± 0.11) but not significantly so (P=0.12). On immunostaining,activated microglia were exclusively observed in the R but not in the L ST.

Conclusions Both PBR28 and FEPPA appear promising PBR ligands for PET brain imaging of microglia activation.