RT Journal Article SR Electronic T1 Preclinical characterization of [18F]DPA-714: In vitro and in vivo studies JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1170 OP 1170 VO 52 IS supplement 1 A1 Marie-Anne Peyronneau-Schollhorn A1 Wadad Saba A1 Sebastien Goutal A1 Annelaure Damont A1 Frédéric Dollé A1 Michael Kassiou A1 Michel Bottlaender A1 Heric Valette YR 2011 UL http://jnm.snmjournals.org/content/52/supplement_1/1170.abstract AB 1170 Objectives Imaging peripheral benzodiazepine receptors is of considerable clinical interest in several neurodegenerative diseases. In animal models of neuroinflammation, [18F]DPA-714 was previously shown to be a good candidate for imaging activated microglia. In the present study, in vivo and ex vivo biodistribution and metabolism of the radiotracer were investigated in rodents and non human primates to further validate the use of this radioligand. Methods The biodistribution of [18F]DPA-714 was determined by PET whole body imaging in baboons. For metabolic studies, plasma and brain extracts were analyzed by radio-HPLC. The structural characterization of the main radiometabolites was previously performed by LC/MS/MS analyses (1). Results Whole body imaging in two baboons showed a high radioactivity level in the gallbladder at 40 min (SUV 6.4) and in the urinary bladder (SUV 3) suggesting the role of the hepatobiliary system and the kidneys for excretion. Bones displayed a significant [18F]fluoride uptake (SUV 1.5), generated upon O-dealkylation of the tracer, as demonstrated by microsomal incubations analyses. In baboon arterial plasma, [18F]DPA-714 was rapidly converted into three radiometabolites. Only 30% of the radiotracer remained intact at 60 min post injection. The most abundant radiometabolite was highly polar and represented 40% of the radioactivity. This acid derivative was formed in plasma by further oxidation of a hydroxylated metabolite. In the rat brain, the same acid radiometabolite was detected at 120 min post injection, accounting for 15% of the total radioactivity. Conclusions [18F]DPA-714 is rapidly converted into several radiometabolites in rats and baboons. One of them crossed the BBB without a specific regional accumulation. O-deethylation generated an unlabelled compound concomitantly with [18F]fluoroacetate, leading to free [18F]fluoride that accumulated in the bones. This in vivo behavior of [18F]DPA-714 should be considered when quantifying PET kinetics in humans