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Introduction: The dysfunction of glycogen synthase kinase-3β (GSK-3β) has been implicated in a number of diseases, including Alzheimer’s disease. The ability to non-invasively quantify GSK-3β activity in vivo is therefore of critical importance, and this work is focused upon development of inhibitors of GSK-3β radiolabeled with carbon-11 to examine quantification of the enzyme using positron emission tomography (PET) imaging. Methods: 11C PyrATP-1 was prepared from the corresponding desmethyl-piperazine precursor in an automated synthesis module. In vivo rodent and primate imaging studies were conducted on a Concorde MicroPET P4 scanner to evaluate imaging properties and in vitro autoradiography studies with rat brain samples were carried out to examine specific binding. Results: 2035±518MBq (55±14mCi) of [11C]PyrATP-1 was obtained (1%–2% non-corrected radiochemical yield at end-of-synthesis based upon [11C]CO2) with high chemical (>95%) and radiochemical (>99%) purities, and good specific activities (143±52GBq/μmol (3874±1424Ci/mmol)), n=5. In vivo microPET imaging studies revealed poor brain uptake in rodents and non-human primates. Pretreatment of rodents with cyclosporin A resulted in moderately increased brain uptake suggesting Pgp transporter involvement. Autoradiography demonstrated high levels of specific binding in areas of the rodent brain known to be rich in GSK-3β. Conclusion: 11C PyrATP-1 is readily synthesized using standard carbon-11 radiochemistry. However the poor brain uptake in rodents and non-human primates indicates that the radiotracer is not suitable for the purposes of quantifying GSK-3β in neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

4-[18F]Fluoro-m-hydroxyphenethylguanidine([18F]4F-MHPG, [18F]1) is a newcardiac sympathetic nerve radiotracer with kinetic properties favorablefor quantifying regional nerve density with PET and tracer kineticanalysis. An automated synthesis of [18F]1was developed in which the intermediate 4-[18F]fluoro-m-tyramine ([18F]16) was preparedusing a diaryliodonium salt precursor for nucleophilic aromatic [18F]fluorination. In PET imaging studies in rhesus macaquemonkeys, [18F]1demonstrated high qualitycardiac images with low uptake in lungs and the liver. Compartmentalmodeling of [18F]1kinetics provided net uptakerate constants Ki(mL/min/g wet), andPatlak graphical analysis of [18F]1kineticsprovided Patlak slopes Kp(mL/min/g).In pharmacological blocking studies with the norepinephrine transporterinhibitor desipramine (DMI), each of these quantitative measures declinedin a dose-dependent manner with increasing DMI doses. These initialresults strongly suggest that [18F]1can providequantitative measures of regional cardiac sympathetic nerve densityin human hearts using PET. [ABSTRACT FROM AUTHOR]