Radiolabeled Procedure Of¹¹C-DPOD And Image Analysis Of Positron Emission Tomography In Alzheime’s Disease

Part Ⅰ. Synthesis and quality control of11C-DPOD.Aim:An11C-labeled PET Aβ imaging agent titled DPOD, a new series of11C-6-OH-BTA-1derivatives, could facilitate the clinical evaluation of AD pathology. Here we describe the synthesis of11C-DPOD and present the results of quality control with11C-DPOD. Methods:11C-Triflate-CH3was bubbled into2mg precursor DPOD which was dissolved in0.1mg methyl ethyl ketone to generate11C-DPOD in a V-tube at hot temperature (about80℃). Results:11C-DPOD is a colourless transparnt liquid with ethyl alcohol about10%,pH value of7.0.The radiochemical purity was over98%and the average radiolabeling yield was10%to15%. Conclusions:11C-DPOD radioactivity of brain could be synthesized by ourselves and used to further study in the animal or human study.Part Ⅱ. Pharmacokinetics and biodistribution of11C-DPOD in the normal animalObjective:To exolpre the pharmacokinetics and biodistribution of the new agent,11C-DPOD in vivo. Methods:Injecting11C-DPOD in the transgenic and normal aging mice by tail.Then, using PET/CT to image radioactive consentration of transgenic and senile mice. All data were analyzed by stata10.0software (P<0.05). Results:There was no difference in pharmacokinetics between transgenic and senile mice after injecting11C-DPOD. Conclusion:11C-DPOD radioactivity of brain was synthesized by ourselves and washed out quickly thereafter in both transgenic and senile micePart Ⅲ.11C-DPOD PET dynamic imaging for aged cynomolgus monkeysObjective:To study the metabolism of11C-DPOD PET dynamic imaging for aged cynomolgus monkeys brain and compared radioactive density ration in aged cynomolgus monkeys brain between11C-DPOD and11C-PIB. Methods:11C-DPOD and11C-PIB were examined on four aged adult male cynomolgus monkeys using positron emission tomography.Features of the images obtained were analyzed by2physicians of nuclear medicine. The region of interest (ROI) was used to plot the cerebral cortex and infracortical nuclear diagram to calculate and analyze the SUV values for each brain region at different time points. Radioactive distribution in cynomolgus monkeys brain was evaluated by distribution volume ratios(DVR).Results:"C-DPOD and11C-PIB could rapidly pass through the blood-brain barrier and were then quickly cleared from healthy brain tissues. Both tracers showed increased accumulation in the striatum,thalamus,cingulate and pons.After two half-lives,there was no significant difference in monkeys brain between "C-DPOD and11C-PIB.Conclusion:11C-DPOD radioactivity of brain was synthesized by ourselves and washed out quickly thereafter in monkey brains,and there was no difference radioactive density ration in aged cynomolgus monkeys brain between11C-DPOD and11C-PIB.Conclusions(Part Ⅰ-ParⅡ):1.Synthesis of11C-DPOD was of high radiochemical purity and good stability in vitro. All quality criteria of11C-DPOD met the requirements of the positron radionuclide-radiolabeled pharmaceutical, and can be used to further study.2.11C-DPOD could quickly discharge and decrease to the low level in vivo.There was no significant difference of11C-DPOD that distributed in the different regions between transgenic rats and normal rats..3."C-DPOD and "C-PIB could rapidly pass through the blood-brain barrier and were then quickly cleared from healthy brain tissues. Both tracers showed increased accumulation in the striatum,thalamus,cingulate and pons.After two half-lives,there was no significant difference in monkeys brain between11C-DPOD and11C-PIB.4.Synthesis of11C-DPOD and pharmacokinetics study by PET/CT (Clinical type)in small animals had not been reported in literature.Subject Selection and research were original.