Cerebral kinetic and whole-body uptake of the TSPO radioligand 18F-DPA-714 in healthy volunteers

1279 Objectives The translocator protein 18kDa (TSPO) is part of the mictochondrial permeability transition pore, located in the outer mitochondrial membrane. TSPO is ubiquitously expressed in most peripheral organs but only minimally expressed in the healthy brain. Increased levels of TSPO expression have been noted in neuroinflammatory and neurodegenerative conditions coinciding with the activation of microglia. The development and validation of an in vivo biomarker of microglial activation would be a major advance in the detection, evaluation and therapeutic monitoring of neuroinflammatory processes. In this study, we evaluate the whole-body (WB) uptake and cerebral kinetics of the TSPO radioligand 18F-DPA-714. Methods In seven healthy volunteers, cerebral PET scans were performed over 90 min following iv injection of 18F-DPA-714 (245±45 MBq). Two subjects were submitted to a WB acquisition. Blood samples were collected from 2 subjects throughout the PET acquisition. ROI were defined over cerebral structures and visible organs to obtain mean activity curves and SUV for brain and WB scans, respectively. Results Formation of blood metabolites was slow with only 20% metabolites at 20 min pi. The % of injected dose was approximately 0.02/ml of cerebral cortex. Maximum cerebral uptake was observed 5 min pi, followed by two decreases phases: a rapid phase between 5 and 30 min; followed by a slower phase from 30 min until the end of PET acquisition. On WB images, high activity was seen in gall bladder, heart and intestinal wall, spleen, spine and kidneys. The main routes of elimination are hepatobiliary and urinary. Conclusions The results of this preliminary study demonstrate that 18F-DPA-714 has excellent brain uptake with high-affinity for the TSPO which are favorable characteristics for a TSPO PET radioligand for in vivo neuroinflammatory evaluation. Research Support EC-FP6-project DiMI, LSHB-CT-2005-51214