In vivo evaluation of [C-11]preladenant for imaging of adenosine A(2A) receptors in rat brain: kinetic modelling and test/retest variability

488 Objectives Adenosine A2A receptor (A2AR) is studied as a therapeutic and diagnostic target in many brain disorders. Recently, we have synthesized [11C]preladenant, a PET ligand with high affinity and selectivity for the A2AR. The present study aims to further evaluate [11C]preladenant in rat brain. Methods Rats were i.v. injected with [11C]preladenant and a 60 min dynamic PET scan was started. Arterial blood samples were obtained during the scan to provide the input function for kinetic modelling. The distribution volume (VT) was obtained by modelling with a 2-tissue-compartment model (2TCM) and Logan plot. The simplified reference tissue model (SRTM) and the reference tissue Logan plot (RLogan) were used to estimate the binding potential (BPND) in striatum. Cerebellum, midbrain, hippocampus and occipital cortex were tested as reference regions. BPNDs obtained from the reference models were compared with BPNDs calculated from the VT determined with the Logan plot. Test/retest variability was defined as 2*|BPND, test - BPND, retest|/(BPND, test + BPND, retest). Results Tracer kinetics was well described by the 2TCM and Logan plot. VTs obtained from the 2TCM and the Logan plot were comparable, with highest value in striatum (~10) and lower values in all extrastriatal regions (~1.5-2.5), suggesting that the tracer distribution is consistent with A2AR regional expression. BPNDs estimated from the SRTM and RLogan were in agreement with BPNDs calculated from VT (eg. BPND, Logan = BPND, RLogan = 5.7 ± 0.6, BPND, SRTM = 5.5 ± 0.5, using midbrain as reference region). Midbrain as the reference region displayed highest BPND and lowest standard deviation in striatum. Test/retest variability values were ~4.5%, except for hippocampus as the reference region (9.1%). Therefore, midbrain seems to be the preferred reference region to quantify A2ARs with a reference tissue model. Conclusions With [11C]preladenant-PET it is possible to non-invasively quantify A2ARs in the brain using a reference tissue model.