The Clinical Value Of ¹⁸F-AV45 PET Imaging In The Diagnosis Of Alzheimer’s Disease

Objective:Based on Tracerlab FX_F-Nplatform,edit the synthesis procedure and purification procedure by yourself,improve the synthesis method and purification method to realize the simple,stable and repeated production of[¹⁸F]AV-45 preparation,establish a reliable and sensitive quality control method to control the quality of the finished product,and ensure the safety of clinical use.The[¹⁸F]AV-45 preparation can be stably and repeatedly produced for many times,and the produced[¹⁸F]AV-45 can meet the main indicators of intravenous radiopharmaceutical preparations without changing the process.Compare the application value of tracers prepared by two different purification methods in screening and early diagnosis of Alzheimer’s disease.Methods:1)When purified by preparative HPLC,the O-toluenesulfonated precursor（1 mg）was subjected to nucleophilic radiofluorination at 115°C in anhydrous dimethyl sulfoxide,and then the hydrochloric acid solution hydrolyzed the protective group.The neutralized reaction mixture was purified by the preparation liquid phase,and then enriched by C18purification column to obtain a relatively pure[¹⁸F]AV-45 product with high specific activity.When purified by SPE,the O-toluenesulfonated precursor（1 mg）is subjected to nucleophilic radiofluorination reaction in anhydrous dimethyl sulfoxide at 120°C,then the sulfuric acid solution hydrolyzes the protective group,and the neutralized reaction mixture is purified by solid phase extraction to obtain a relatively pure and high specific activity[¹⁸F]AV-45 product.2)From January 2021 to January 2022,50 patients with Alzheimer’s disease（AD group）and 20 healthy controls（HC group）were collected who prepared[¹⁸F]-AV45 and PET-CT by two pure methods.The distribution characteristics in healthy people and AD people were analyzed by visual analysis and semi-quantitative method.3)Collect 50 cases of Alzheimer’s disease（AD group）and 20 cases of healthy control（HC group）diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2022 to December 2022,and perform[¹⁸F]-FDG and[¹⁸F]-AV45 imaging.According to the MMSE score of patients in AD group,patients in mild dementia,moderate dementia and severe dementia group were analyzed for clinical data and PET-CT imaging results of four groups of patients.Results:1)Four consecutive radiochemical synthesis were carried out during purification by preparative HPLC.The average production time of[¹⁸F]AV-45 preparation was 60 minutes,the radiochemical yield was 14.8%±2.1%（n=4）,and the radiochemical purity was more than 95%.Other important quality control indicators met the requirements of intravenous administration of radioactive drugs.During SPE purification,six consecutive radiochemical synthesis were carried out.The average production time of[¹⁸F]AV-45 preparation was 52 minutes,the radiochemical yield was 14.2%±2.7%（n=6）,and the radiochemical purity was more than95%.Other important quality control indicators met the requirements of intravenous administration of radiopharmaceuticals.2)There was a statistically significant difference in education level and MMSE score between the two groups of subjects based on baseline data comparison（P<0.05）.The results of visual analysis showed that the tracer prepared by HPLC method showed an increase in gray matter metabolism and unclear boundary with white matter in the healthy group.The sensitivity for diagnosing AD was 73.3%,specificity was 85%,positive predictive value was 88%,negative predictive value was68%,accuracy was 78%,and there was good consistency with clinical results.The Kappa value was 0.560;The metabolism of drugs prepared by solid-phase extraction method in white matter is higher than that in gray matter,with clear boundaries between gray and white matter.The sensitivity for diagnosing AD is 86.7%,specificity is 100%,positive predictive value is 100%,negative predictive value is 83.3%,accuracy is 92%,and there is good consistency with clinical results.The Kappa value is 0.839.Semi quantitative analysis:The SUVR values of the tracer HC group prepared by HPLC method in the frontal lobe,anterior cuneiform lobe,posterior cingulate cortex,temporal lobe,and occipital lobe were higher than those of the SPE method,with statistical differences（P<0.05）.The SUVR values in the frontal lobe and basal ganglia of the AD group were higher than those of the SPE method,with statistical differences（P<0.05）.HPLC method:AD group and HC group have high differential diagnostic value in the parietal lobe（AUC=0.940）.SPE method:AD group and HC group have high differential diagnostic value in the temporal lobe（AUC=0.969）.3)There were significant differences in age,fasting glucose,triacylglycerol,high-density lipoprotein,MMSE and Mo CA scores among the four groups at baseline（P<0.05）.The semi quantitative analysis results show that[¹⁸F]-FDG has good diagnostic value in distinguishing between healthy controls and mild dementia,as well as the temporal lobe;The frontal lobe has diagnostic value in distinguishing mild dementia from moderate dementia;The basal ganglia has high diagnostic value in distinguishing between moderate and severe dementia;[¹⁸F]-AV45has good diagnostic value in distinguishing between healthy controls and mild dementia,and the posterior cingulate cortex;Distinguishing mild dementia from moderate dementia has high diagnostic value in the temporal lobe;The frontal lobe has high diagnostic value in distinguishing between moderate and severe dementia.The combination of two tracers,the healthy group and the mild dementia group,has good diagnostic value in the frontal lobe,parietal lobe,anterior cuneiform lobe,posterior cingulate cortex,temporal lobe,and occipital lobe,and has high diagnostic value in the basal ganglia.The sensitivity of the anterior cuneiform lobe,posterior cingulate cortex,and temporal lobe is 100%;The specificity of the frontal lobe and posterior cingulate cortex is 100%.The mild dementia group and the moderate dementia group have high diagnostic value in the frontal lobe,posterior cingulate cortex,and temporal lobe.The specificity of the occipital lobe is 100%.The moderate dementia group and severe dementia group have good diagnostic value in the frontal lobe,parietal lobe,occipital lobe,and basal ganglia.The sensitivity of the basal ganglia is 100%;The specificity of the parietal lobe and posterior cingulate cortex is100%.Conclusion:Based on the Tracerlab FX_F-Nplatform,the synthesis program and crude product purification program were edited by ourselves.Through the screening and optimization of the separation and purification system,the screening and optimization of the separation and analysis system,the automatic radiochemical synthesis,the SPE purification method,and the quality control of the preparation,the synthesis method and purification method were improved,and the intravenous injection grade[¹⁸F]-AV45 was successfully prepared.It makes the whole synthesis process of[¹⁸F]AV-45 simpler,more stable,more time-saving and labor-saving.The tracer prepared by SPE method and the tracer prepared by HPLC method can be better used for the diagnosis of Alzheimer’s disease,but in disease screening,SPE method is better.Dual probe PET CT imaging can provide early diagnosis of AD,and in clinical staging,[¹⁸F]AV-45 PET CT has good clinical value.