Polymergestützte Synthese von unsymmetrischen n.c.a. (73,75Se) Selenoethern zur Markierung von Aminosäuren

The synthesis of n.c.a. selenium-73/75 labelIed methionine and of a selenoalkylation agent have been performed according to a reaction including a primary, polymer supported alkylation step. The selenium-75 was produced through the $^{75}$As(p,n)-process and separated as [$^{75}$Se] selenium dioxide by thermochromatography. The [$^{75}$Se]SeO$_{2}$- sublimate was dissolved in hydrochloric acid and reduced with sulfur dioxide to obtain elemental n.c.a. selenium-75, which was extracted into benzene. Reaction of the elemental n.c.a. selenium-75 with polymeric bound triphenylphosphine led to the formation of the corresponding [$^{75}$Se] triphenylphosphinselenide in a nearly quantitative yield. In the primary, heterogenous alkylation step the [$^{75}$Se]methylselenotriphenylphosphonium salt (TPPSeMeOTf) was formed via methyltriflate as alkylation reagent. The phosphonium salt was hydrolised under alkaline condi tions yielding [$^{75}$Se]methylselenide anion (MeSe$^{-}$) in a radiochemical yield of up to 70%. The asymmetrical [$^{75}$Se]selenoethers were synthesized in homogenous phase through the reaction of the [$^{75}$Se]MeSe$^{-}$ with propylhalides in radiochemical yields up of to 55%. In the case of n.c.a. [$^{75}$Se]selenomethionine, which was produced for the first time, the secondary alkylation step led to the formation of protected [$^{75}$Se]selenomethionine by using N-BOC-2-amino-4-bromo-butyric acid ethylester as precursor and [$^{75}$Se]MeSe$^{-}$ (generated from the polymeric bound [$^{75}$Se]TPPSeMeOTf) as [$^{75}$Se]selenation reagent. After acid hydrolysis the selenomethionine was obtained in radiochemical yields of 30%, in a radiochemical purity of about 95%, and with a specific activity >185 GBq/mmol. A selenium-75 labelled prosthetic group was synthesized in radiochemical yields of 48% by the reaction of 1-chloro-3-iodopropane with the [$^{75}$Se]selenation reagent [$^{75}$Se]MeSe$^{-}$. This reagent was prepared from the polymeric bound [$^{75}$Se]TPPSeMeOTf using TBAH. For labelling amino functions via [$^{75}$Se]selenoalkylation the [$^{75}$Se]selenated propyl chloride has to be transfered into the iodide with sodium iodide, which was performed in radiochemical yields of 90%. After the reaction of [$^{75}$Se]-l-iodo-3- (methylseleno)propane with butylamine or with N$^{\alpha}$-, O-protected lysine in DMF at 80$^{\circ}$ the [$^{75}$Se]methylselenopropylated products were radiochemical yields of 95% and 90%, respectively

Feasibility of [18F]-2-Fluoro-A85380-PET Imaging of Human Vascular Nicotinic Acetylcholine Receptors In Vivo

ObjectivesThe aim of this feasibility study was to evaluate [18F]-2-Fluoro-A85380 for in vivo imaging of arterial nicotinic acetylcholine receptors (nAChRs) in humans. Furthermore, potentially different vascular uptake patterns of this new tracer were evaluated in healthy volunteers and in patients with neurodegenerative disorders.Background[18F]-2-Fluoro-A85380 was developed for in vivo positron emission tomography (PET) imaging of nAChR subunits in the human brain. These nAChRs are also found in arteries and seem to mediate the deleterious effects of nicotine as a part of tobacco smoke in the vasculature. It has been previously shown that uptake patterns of the radiotracer in the brain differs in patients with neurodegenerative disorders compared with healthy controls.Methods[18F]-2-Fluoro-A85380 uptake was quantified in the ascending and descending aorta, the aortic arch, and the carotids in 5 healthy volunteers and in 6 patients with either Parkinson's disease or multiple system atrophy, respectively, as the maximum target-to-background ratio. The maximal standardized uptake value values, the single hottest segment, and the percent active segments of the [18F]-2-Fluoro-A85380 uptake in the arteries were also assessed.Results[18F]-2-Fluoro-A85380 uptake was clearly visualized and maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly higher uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [18F]-2-Fluoro-A85380 uptake in the patient group when comparing single arterial territories but not when all arterial territories were pooled together.Conclusions[18F]-2-Fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Vascular nAChR density seems to be lower in patients with Parkinson's disease or multiple system atrophy. Once confirmed in larger study populations and in the experimental setting, this approach might provide insights into the pathogenic role of nAChRs in the human vasculature