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The Suzuki‐type cross coupling reaction is a palladium‐mediated multistep reaction that has been used to synthesize several 11C‐labeled tracers for PET. However, the impact of the selected organoborane reagent and reaction medium on the radiochemical yield (RCY) has not been thoroughly investigated. To bridge this gap, we studied the synthesis of 1‐[11C]methylnaphthalene using four different organoborane precursors in reactions performed in DMF/water and THF/water. In the synthesis of 1‐[11C]methylnaphthalene, the best radiochemical yields (RCYs), approximately 50%, were obtained with boronic acid and pinacol ester precursors, whereas less than 4% RCY was obtained when performing the reaction with the N‐methylimidodiacetic acid boronic ester (MIDA ester) precursor. 1‐[11C]methylnaphthalene was obtained in higher yields in almost all syntheses performed in THF/water as compared to DMF/water. This observation was in line with previously reported results for [11C]UCB‐J, a tracer for the synaptic vesicle glycoprotein 2A (SV2A) receptor, that also was obtained in higher RCY when synthesized in THF/water. The same trend was observed with [11C]cetrozole, where the RCY was more than doubled in THF/water compared to the previously published synthesis performed in DMF. These results suggest that THF/water could be the preferred reaction medium when producing PET tracers via the Suzuki‐type coupling reaction. [ABSTRACT FROM AUTHOR]

19F/18F isotope exchange is a useful method to label drug molecules containing 19F-fluorine with 18F without modifying the drug molecule itself. Sphingosine-1-phosphate (S1P) is an important cellular mediator that functions by signaling through cell surface receptors. S1P is involved in several cell responses and may be related to many central nervous system disorders, including neural malfunction in Alzheimer's disease. In this study, [18F]1-benzyl- N-(3,4-difluorobenzyl)-2-isopropyl-6-(2-methoxyethoxy)-1 H-indole-3-carboxamide, a novel 18F-labeled positron emission tomography tracer for the S1P3 receptor, was successfully synthesized using the 19F/18F isotope exchange reaction. Parameters of the reaction kinetics were studied, and correlations between the initial 18F-activity, the amount of precursor, radiochemical yield and specific activity (SA) were determined. Contrary to expectations, high initial 18F-activity decreased the radiochemical yield, and only a minor increase of SA occurred. This is most probably due to the complexity of the molecule and the subsequent susceptibility to radiolytic bond disruption. On the basis of the present results, a convenient condition for the 19F/18F exchange reaction is the use of 2 µmol precursor with 20 GBq of 18F-activity. This afforded a radiochemical yield of ~10% with an SA of 0.3 GBq/µmol. Results from this study are of interest for new tracer development where high initial 18F-activity and 19F/18F isotope exchange is used. [ABSTRACT FROM AUTHOR]

Indirect experimental evidence suggests that drugs acting on the α2C-adrenoceptor could be useful in the treatment of neuropsychiatric disorders such as depression and schizophrenia. In rodent brain, the highest levels of α2C-adrenoceptors are found in the striatum, with lower levels in cerebral cortex and hippocampus. In human brain, because of the poor subtype-selectivity of the available α2-adrenoceptor ligands, the localization of α2C-adrenoceptors has remained unknown. Recently, a selective α2C-adrenoceptor antagonist, JP-1302, was characterized, and to assess the presence of α2C-adrenoceptors in human brain, we performed competition binding in vitro receptor autoradiography with JP-1302 and the α2-adrenoceptor subtype nonselective antagonist [ethyl-3H]RS79948-197 on rat and human postmortem brain sections. In striatum of both species, JP-1302 vs. [ethyl-3H]RS79948-197 competition binding was biphasic, identifying high- and low-affinity binding sites, whereas in cortex and cerebellum, only low-affinity binding sites were detected. The results indicate that a significant portion of the α2-adrenoceptors in striatum is of the α2C subtype, whereas non-α2C-adreocneptors predominate in cortex and cerebellum. Because the α2C-adrenoceptor subtype distribution pattern appears to be conserved between rodents and humans, results obtained from studies on the role of the α2C-adrenoceptor in rodent models of neuropsychiatric disorders may be relevant also for human diseases. Synapse 62:508-515, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]