TY - JOUR T1 - 18F-Labeling and evaluation of novel 18F-labelled MDL 100907 derivatives as potential 5-HT2A antagonists JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1219 LP - 1219 VL - 50 IS - supplement 2 AU - Matthias Herth AU - Fabian Debus AU - Markus Piel AU - Hartmut Lueddens AU - Frank Roesch AU - Vasko Kramer Y1 - 2009/05/01 UR - http://jnm.snmjournals.org/content/50/supplement_2/1219.abstract N2 - 1219 Objectives Beside [18F]altanserin, [11C]MDL 100907 is the tracer of choice to image the 5-HT2A receptor. The selectivity of MDL 100907 prefers this tracer. Nevertheless, it is limited by the short half-life of carbon-11. We have recently synthesized analogs of MDL 10007 combining the advantages of the superior selectivity of MDL 100907 over altanserinand the better isotopic properties of 18F. Herein, we want to report the radiolabelling and preliminary evaluation studies of various 18F-MDL 100907 derivatives. Methods Several MDL 100907 derivatives were labelled with F-18. Purification was carried out via HPLC and cartridge. Autoradiography, metabolism, biodistribution and µPET studies were conducted in rats. Results Optimization of the radiochemical reaction conditions yielded about 80–90 %. The final formulation took no longer than 100 minutes and provided the labeled compounds with a purity > 96% and a As between 15 – 20 GBq/µmol. Autoradiographic studies for promising derivatives MH.MZ (Ki=9.0 nM) and (R)-MH.MZ (Ki=0.7 nM) showed excellent binding, whereas surprisingly MA-1 (Ki=3.1 nM) showed an unfavourable distribution . This is probably due to the increased lipohilicity. µPET experiments including metabolism studies showed a BP of 1.5 of [18F]MH.MZ and 1.8 of (R)-[18F]MH.MZ, fast metabolism and an brain uptake of 0.6 % ID/g tissue. Conclusions [18F]MH.MZ and (R)-[18F]MH.MZ could be obtained as an injectable solution in RCY of about 40% within a synthesis time of about 100 minutes in a purity of > 96%. Both tracers showed excellent binding properties in in vitro, ex vivo and in vivo experiments. However, (R)-[18F]MH.MZ is the more valuable tracer. ER -