Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation

Introduction: The translocator protein 18 kDa (TSPO), although minimally expressed in healthy brain, is up-regulated in pathological conditions, coinciding with microglial activation. It is thereby a suitable in vivo biomarker of neuroinflammation for detection, evaluation and therapeutic monitoring of brain diseases. We aimed to estimate the radiation dosimetry of the positron emission tomography (PET) TSPO radioligand [F-18]DPA-714, and we evaluated in healthy volunteers its whole-body uptake and cerebral kinetics. Methods: Biodistribution data from mice were used for the prediction of radiation dosimetry. In human studies, a 90-min dynamic PET scan was performed in seven healthy volunteers after injection of [F-18]DPA-714 (245 +/- 45 MBq). Arterial and venous samples were collected from two subjects, and two additional subjects were submitted to whole-body acquisition. Regions of interest were defined over cerebral structures to obtain mean time activity curves and to estimate the distribution volume ratios by Logan graphical analysis, and over peripheral organs to obtain standard uptake values. Results: The effective dose estimated from biodistribution in mice was 17.2 mu Sv/MBq. Modeling of regional brain and plasma data showed good in vivo stability of [F-18]DPA-714 in humans, with only 20% of blood metabolites 20 min postinjection (p.i.). Maximum cerebral uptake was observed 5 min p.i., followed by two decreasing phases: a rapid washout (5-30 min) followed by a slower phase for the remainder of PET acquisition. Whole-body images demonstrate high activity in the gallbladder, heart, spleen and kidneys. Conclusions: This initial study in humans shows that [F-18]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable effective dose estimation. Therefore, [F-18]DPA-714 could provide a sensitive measure of neuroinflammatory changes in subsequent clinical investigations. (C) 2012 Elsevier Inc. All rights reserved.