Quantitative, Preclinical PET of Translocator Protein Expression in Glioma Using ¹⁸F-N-Fluoroacetyl-N-(2,5-Dimethoxybenzyl)-2-Phenoxyaniline

T2-weighted (A) and diffusion-weighted (B) MR images of rat bearing C6 glioma in right brain hemisphere. (C) PET demonstrates elevated uptake of ¹⁸F-PBR06 in tumor tissues, compared with contralateral brain (summed dynamic scan, 0–90 min). (D) ¹⁸F-PBR06 time–activity curves and model fit (3 compartment, 4 parameter) for tumor (blue), contralateral brain (green), and plasma (red) demonstrate rapid tracer uptake in tumor and normal brain, followed by rapid clearance from plasma and normal tissue. Comparatively slow washout of ¹⁸F-PBR06 was observed in tumor tissues, facilitating significant contrast between tumor and contralateral brain. (E) Serial histologic analysis of typical C6 glioma by standard hematoxylin and eosin staining (inset) and immunohistochemistry for TSPO expression illustrating elevated TSPO expression within tumor tissue, compared with contralateral brain. (F) Western blot assay illustrating relative TSPO protein expression levels in matched contralateral brain tissue and C6 glioma tissues harvested from similar C6 glioma–bearing rat cohorts. Color bar in B corresponds to units of diffusion (μm²/ms). B = brain tissue; T = C6 glioma tissue.

In vivo displacement of ¹⁸F-PBR06 in C6 glioma–bearing cohort. (A) T2-weighted MR image of rat bearing C6 glioma in right brain hemisphere. Relative ¹⁸F-PBR06 uptake before (B) and after (C) intravenous infusion of excess PBR06. (D) ¹⁸F-PBR06 time–activity curves generated for tumor (blue), contralateral brain (green), and plasma (red). Immediately after infusion of ¹⁸F-PBR06, tumor activity drops to approximately 25% of maximum uptake level, accompanied by minor, transient tracer influx observed in contralateral brain and elevated plasma activity. Data are representative of repeated imaging studies.

HPLC radiochromatograms illustrating plasma composition of parent ligand (¹⁸F-PBR06) and primary radiometabolite ¹⁸F⁻ as function of time after tracer injection. At 2 and 25 min after injection of ¹⁸F-PBR06, free ¹⁸F⁻ (25% at 2.8 min, 62% at 30 min) and parent ligand (75% at 2.8 min, 38% at 30 min) are detectable in plasma. After infusion of PBR06 at 30 min after administration of ¹⁸F-PBR06, both fraction of ¹⁸F-PBR06 (57% at 45 min) and ¹⁸F⁻ (43% at 45 min) were elevated in plasma. Dashed gray line = 2 min after ¹⁸F-PBR06 injection; dashed black line = 25 min after ¹⁸F-PBR06 injection; solid black line = 45 min after ¹⁸F-PBR06 injection and 15 min after cold PBR06 injection.