Quantification of translocator protein (18 kDa) in the human brain with PET and a novel radioligand, ¹⁸F-PBR06

Translocator protein (TSPO) (18 kDa), formerly called the peripheral benzodiazepine receptor, is upregulated on activated microglia and macrophages and is, thus, a biomarker of inflammation. We previously reported that an ¹¹C-labeled aryloxyanilide (half-life, 20 min) was able to quantify TSPOs in the healthy human brain. Because many PET centers would benefit from a longer-lived ¹⁸F-labeled radioligand (half-life, 110 min), the objective of this study was to evaluate the ability of a closely related aryloxyanilide (¹⁸F-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2- phenoxyaniline [¹⁸F-PBR06]) to quantify TSPOs in the healthy human brain. Methods: A total of 9 human subjects were injected with ¹⁸F-PBR06 (∼185 MBq) and scanned for 5 h, with rest periods outside the camera. The concentrations of ¹⁸F-PBR06, separated from radiometabolites, were measured in arterial plasma. Results: Modeling of regional brain and plasma data showed that a 2-tissue-compartment model was superior to a 1-tissue-compartment model. Even if data for all time points were used for the fitting, concentrations of brain activity measured with PET were consistently greater than the modeled values at late (280-300 min) but not at early time points. The greater values may have been caused by the slow accumulation of radiometabolites in the brain. To determine an adequate time for more accurate measurement of distribution volume (V_T), which is the summation of receptor binding and nondisplaceable activity, we investigated which scan duration would be associated with maximal or near-maximal identifiability. We found that a scan of 120 min provided the best identifiability of V_T (∼;2%). The images showed no significant defluorination. Conclusion: ¹⁸F-PBR06 can quantify TSPOs in the healthy human brain using 120 min of image acquisition and concurrent measurements of radioligand in plasma. Although brain activity is likely contaminated with radiometabolites, the percentage contamination is thought to be small (<10%), because values of distribution volume are stable during 60-120 min and vary by less than 10%. ¹⁸F-PBR06 is a longer-lived and promising alternative to ¹¹C-labeled radioligands to measure TSPOs as a biomarker of inflammation in the brain.