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Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.
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Objective:To evaluate the diagnostic value of 11C-choline PET/CT brain imaging for localization of epileptogenic foci in hippocampal sclerosis-refractory temporal lobe epilepsy (HS-RTLE), and compare it with 18F-FDG and 11C-flumazeni (FMZ) PET/CT. Methods:From March 2017 and June 2020, a total of 62 patients (39 males, 23 females, age (30.3±11.2) years) with pathologically confirmed HS-RTLE in General Hospital of Northern Theater Command were retrospectively analyzed. All patients were preoperatively treated with multiple radionuclide ( 18F-FDG, 11C-FMZ, 11C-choline) PET/CT brain imaging. 11C-choline PET imaging was used to acquire dynamic imaging data and time-activity curve (TAC) of 11C-choline in bilateral hippocampal regions were drawn. With postoperative pathology as the " gold standard" , the positive detection rates and localization diagnostic efficacies of three radionuclide imaging agents for epileptogenic foci were analyzed. Then a prospective study including 46 patients (27 males, 19 females; age (32.9±11.9) years; between May 2019 and August 2020; General Hospital of Northern Theater Command) with drug-refractory epilepsy caused by clinically suspected hippocampal sclerosis was performed. The examination method was the same as that of retrospective study. Using intracranial electrode implantation or postoperative pathology as " gold standard" , the diagnostic efficacy of 11C-choline TAC for localization of epileptogenic foci was verified, and ROC curve was drawn to evaluate the diagnostic value of three imaging agents for HS-RTLE epileptogenic foci. χ 2 test and Fisher exact probability method, Delong test were used to analyze the data. Results:In the retrospective study, the positive detection rate of 18F-FDG PET/CT was higher than that of 11C-choline PET/CT (100%(62/62) vs 85.48%(53/62); P=0.003), and the localization accuracies of 11C-choline and 11C-FMZ PET/CT were both higher than that of 18F-FDG PET/CT (100%(53/53), 96.61%(57/59) vs 33.87%(21/62); both P<0.001). In the prospective study, 25 of 46 patients were diagnosed as HS-RTLE and 21 were non-HS induced epilepsy. The specificities of 11C-choline, 11C-FMZ and 18F-FDG PET/CT were 100%(21/21), 90.48%(19/21), 33.33%(7/21), respectively. The AUCs of 11C-choline and 11C-FMZ PET/CT were significantly higher than that of 18F-FDG PET/CT (0.920, 0.912, 0.627; z values: 4.93, 5.16, both P<0.01). Conclusions:11C-choline PET/CT can be used in the preoperative localization of epileptic foci. Compared with 18F-FDG and 11C-FMZ PET/CT, the specificity of 11C-choline PET/CT is higher, and the negative imaging of 11C-choline is more significant for exclusion.
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Objective:To realize a fully automated synthesis of 11C-meta-hydroxyephedrine (mHED) and to perform imaging studies with it. Methods:11C-mHED was prepared by the 11CH 3-triflate method. The crude product was purified by semi-preparative high performance liquid chromatograph (HPLC) to obtain the final product. The radiochemical purity and specific activity were determined by radio-HPLC. The myocardial uptake and excretion process of the agent were monitored by microPET/CT imaging on 5 normal SD rats. The clinical imaging value was evaluated using PET/CT imaging in a patient (male, 42 years old) with myocardial infarction. Results:The automated synthesis of 11C-mHED was realized by a commercial synthesizer. The total synthesis time was about 30 min. The radiochemical yield was (15±2)% (non-decay corrected, n=10) and the radiochemical purity was greater than 98%. The specific activity was about 65 GBq/mmol. MicroPET/CT imaging in normal SD rats showed the myocardial uptake was highest at 10 min after the injection of imaging agent, and then the imaging agent was gradually excreted from the myocardium through the liver and gallbladder. PET/CT imaging of a patient with myocardial infarction showed an imaging agent defect near the apex in the inferior wall of the left ventricle, which was matched with results of ultrasound and electrocardiogram examination. Conclusions:11C-mHED can be successfully prepared automatically, with high radiochemical yield and specific activity. It can also highly concentrate in the myocardium, and the imaging effect with this agent is good in a patient with myocardial infarction.
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Objective@#To compare the lateralization accuracy and localization accuracy of MRI, interictal 18F-fluorodeoxyglucose(FDG) and 11C-flumazenil(FMZ) PET/CT imaging for refractory epilepsy(REP) in patients with hippocampal sclerosis(HS).@*Methods@#A total of 41 classical HS patients (25 males, 16 females; age: 15-61 years) with REP from General Hospital of Northern Theater Command of PLA between January 2017 and October 2018 were retrospectively analyzed. All patients underwent MRI, interictal 18F-FDG and 11C-FMZ PET/CT imaging, followed by the resection of epileptogenic foci. The pathological diagnosis was taken as the gold standard. Visual and semi-quantitative analyses were used to analyze the images. The lateralization accuracy and localization accuracy of the three imaging methods for epileptogenic foci were calculated and compared(χ2 test).@*Results@#The lateral accuracy and localization accuracy of MRI were 70.73%(29/41) and 60.98%(25/41), those of interictal 18F-FDG PET/CT imaging were 78.05%(32/41) and 70.73%(29/41), and those of interictal 11C-FMZ PET/CT imaging were 100%(41/41) and 100%(41/41), respectively. The interictal 11C-FMZ PET/CT imaging was the best among 3 imaging methods(χ2 values: 1.976-12.902, all P<0.01).@*Conclusions@#All 3 imaging methods have their advantages and limitations. The interictal 11C-FMZ PET/CT imaging has a high value in the localization of classical HSREP, which can significantly improve the diagnostic accuracy of classical HSREP and guide clinical operation.
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Objective To compare the lateralization accuracy and localization accuracy of MRI, interictal 18 F-fluorodeoxyglucose(FDG)and 11 C-flumazenil(FMZ)PET/CT imaging for refractory epilepsy (REP)in patients with hippocampal sclerosis(HS).Methods A total of 41 classical HS patients (25 males,16 females;age:15-61 years)with REP from General Hospital of Northern Theater Command of PLA between January 2017 and October 2018 were retrospectively analyzed.All patients underwent MRI, interictal 18 F-FDG and 11 C-FMZ PET/CT imaging,followed by the resection of epileptogenic foci.The path-ological diagnosis was taken as the gold standard.Visual and semi-quantitative analyses were used to analyze the images.The lateralization accuracy and localization accuracy of the three imaging methods for epilepto-genic foci were calculated and compared(χ2 test).Results The lateral accuracy and localization accuracy of MRI were 70.73％(29 /41)and 60.98％(25 /41),those of interictal 18 F-FDG PET/CT imaging were 78.05％(32 /41)and 70.73％(29 /41),and those of interictal 11 C-FMZ PET/CT imaging were 100％(41 /41)and 100％(41 /41),respectively.The interictal 11 C-FMZ PET/CT imaging was the best among 3 ima-ging methods(χ2 values:1.976-12.902,all P<0.01).Conclusions All 3 imaging methods have their ad-vantages and limitations.The interictal 11 C-FMZ PET/CT imaging has a high value in the localization of classical HSREP,which can significantly improve the diagnostic accuracy of classical HSREP and guide clinical operation.
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Objective To explore the changes of dopamine D2 receptor in dopamine pathway in in-somnia patients and discuss its clinical significance. Methods From January 2016 to December 2016, 15 patients with insomnia (1 male, 14 females, age:(44.3±8.6) years) and 15 gender-/age-matched-healthy volunteers (control group;3 males, 12 females, age:(40.5±9.0) years) were included to undergo resting brain 11C-Raclopride PET/CT imaging. The D2 receptor binding potential (BPND) of the dopamine pathway was calculated by molecular imaging and kinetic analysis toolbox ( MIAKAT) software. The BP ND , Hamilton depression scale ( HAMD) , transient and graphics memory scale results were compared with two-sample t test and Mann-Whitney u test between the two groups. Pearson correlation analysis was used to evaluate the correlation between BPND(nucleus accumbens, caudate nucleus, putamen) and Pittsburgh sleep quality in-dex ( PSQI) , HAMD, course of disease, transient memory and graphical memory scale scores in the patient group. Results The BP ND in bilateral putamen, nucleus accumbens and left caudate nucleus of patients was lower than that of controls( left putamen:z=-2.717, right putamen:z=-2.883, both P<0.01;left nu-cleus accumbens:t=-2.269, right nucleus accumbens:t=-2.410, both P<0.05;left caudate nucleus:t=-2.632,P<0. 05), but the BPND level of right caudate nucleus was not significantly different(z=-0.850, P>0.05) . The scores of HAMD in the patient group were higher than those in control group ( t=10. 273, P<0. 01), while the scores of instantaneous memory (t=-4.888, P<0.01) and graphical memory scale (t=-2.624, P<0.05) were lower. There were significant negative correlations between the BP ND of bilateral nucleus ac-cumbens, caudate nucleus and putamen and the course of insomnia in the patient group ( r range:-0.761 to-0.682, all P<0.01) . Conclusion Patients with insomnia have abnormal neurotransmitter system of dopa-mine D2 and it may play a role in the pathogenesis of insomnia.
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Objective To evaluate the value of SUVmax/ADCmin obtained by 11 C?choline PET/MR imaging in the differential diagnosis of benign and malignant prostate disease. Methods Suspicious prostate cancer patients who underwent PET/MR before transperineal prostate biopsy in People′s Liberation Army General Hospital from April 2014 to January 2015 were observed. Prostate gland was divided into five dis?tricts. A ROI with the diameter of 1 cm was drawn at the highest radioactivity concentration and/or lowest ADC signal area in each district, and SUVmax , ADCmin and SUVmax/ADCmin were then calculated. Taking the pathological results as the gold standard, malignant and benign prostate disease districts were separated. Pearson correlation analysis and two?sample t test were used for statistical analysis. Results Biopsy pathol?ogy showed 9 cases were malignant ( 25 prostate cancer districts, and 20 benign prostate disease districts) , and 6 cases were benign (30 benign prostate disease districts). The SUVmax had a negative correlation with ADCmin( r=-0.521, P<0?05) . The SUVmax/ADCmin of benign and malignant districts was significantly dif?ferent(5.67±3.03 and 13?76±7.13; t=6.9, P<0.01). The ROC AUC for ADCmin, SUVmax and SUVmax/ADCmin were 0?880, 0?809 and 0.898. Using SUVmax/ADCmin of 7.78 as a cutoff, the sensitivity, specificity and accuracy of 11 C?choline PET/MR imaging for differentiating the benign and malignant prostate lesions were 84.0%(21/25), 86.0%(43/50) and 85.3%(64/75), respectively. Conclusions Simultaneous 11C?choline PET/MR could be used for detecting prostate cancer. SUVmax/ADCmin may serve as an effective diag?nostic indicator for differentiating benign and malignant prostate lesions.
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Objective To synthesize 11 C-methyldopamine (MDA) and to explore its feasibility as an agent for cardiac sympathetic nerve imaging.Methods 11 C-MDA was synthesized by direct N-methylation method and purified by semi-preparation reverse HPLC.Thirty Kunming mice were divided into five groups by random number table.The mice were respectively sacrificed at 2,5,10,20 and 30 min after injection of 7.4 MBq 11C-MDA.The lung,liver,spleen,kidney,stomach,intestine,brain,muscle,bone tissues and blood of mice were removed and weighed before radioactive γ-counting.The ％ID/g was calculated.Six Chinese mini-swine were divided into normal group (n=3) and inhibition group (n =3) for myocardial imaging.Mini-swine of inhibition group were injected with 10 mg/kg imipramine hydrochloride at 30 min before 11C-MDA (370 MBq) injection.The data were analyzed with SPSS 15.0 software.Results The synthesis of 11 C-MDA took 45 min with radiochemical yields of (20±3)％.The solution of11 C-MDA was colorless and the pH value was 6.5.The radiochemical purity was more than 98％ and the specific activity was 50 GBq/mmol.The myocardial uptake reached the peak value of (8.78± 1.18) ％ID/g at 2 min after injection of 11 C-MDA in mice.11C-MDA was mainly metabolized through liver and kidney.PET/CT imaging showed that 11 C-MDA was highly uptaken in swine myocardium and could be blocked by imipramine hydrochloride.Conclusions 11C-MDA can be synthesized by a simple and economic method.The high uptake rate of 11 C-MDA in the heart suggests it may be a potential agent for cardiac nerve imaging.
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Objective To explore the impact and value of 11C-MET PET/CT for high-grade glioma in making conformal radiotherapeutic planning compared with MRI.Methods From October 2011 to September 2013,11C-MET PET/CT and MRI were performed in 25 initial glioma cases and 9 recurrent cases.All 34 cases (19 males,15 females) were classified into initial group (n=17),initial surgery group (n=8) and recurrent group (n=9).GTV was outlined using PET/CT images combined with T1 weighted MRI images.Results 11 C-MET PET/CT optimized radiotherapy targets in 22 cases,including 7 initial cases,8 initial surgery cases and 7 recurrent cases.GTV was consistent with the volume of abnormally enhanced region on T1 weighted MRI (VMRI) in 10 initial cases,GTV＞VMRI in 5 cases,and GTV＜VMRI in 2 cases.GTV＜VMR1 in the initial surgery group.GTV was consistent with VMRI in 2 recurrent cases,GTV＞VMRI in 2 cases and GTV＜VMRI in 4 cases; 1 recurrent case's GTV located largely outside the VMRI.Conclusions There are some differences on locating the lesions of high-grade gliomas between 11C-MET PET/CT and MRI.Using 11CMET PET/CT in sketching radiotherapy target could significantly optimize the high grade glioma's radiotherapeutic planning,which may be more valuable in recurrent or operative cases.
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Objective To synthesize podo-and epipodo-podophyllotoxin labeled with 11C and investigate their biodistribution in mice bearing EMT6 tumor by microPET.Methods 11 C-podo-or epipodopodophyllotoxin was synthesized by 11 C-CH3-Triflate mixed with 4'-methyl-demethmyl-podophyllotoxin (podo-and epipodo-) and purified using HPLC.The radiochemical purity (RCP) was analyzed by HPLC.Thirty mice bearing EMT6 tumor were divided into 2 groups and injected with 3.7 MBq 11C-podo-or epipodo-podophyllotoxin.The biodistribution of 11C-podo-or epipodo-podophyllotoxin was evaluated with microPET.The ID％/g was calculated.Paired t test was used to analyze the data.Results The yields of 11C-podo-and epipodo-podophyllotoxin were both ＞90％.The RCP was ＞99％.The biodistribution of 11C-podo-and epipodo-podophyllotoxin was similar with slow blood clearance and high uptake in abdomen.The tumor uptake of 11C-epipodophyllotoxin and 11C-podophyllotoxin at 30 min was (3.63±0.98) ％ID/g and (3.16±0.27) ％ID/g,respectively.The uptake ratio of tumor to blood and to muscle was 0.68 vs 0.62 and 1.52 vs 1.22,respectively.There was no significant difference between the tumor uptake of the two agents (t=0.47,P＞0.05).The result of microPET imaging was consistent with that of mice experiment.Conclusion 11C-podophyllotoxin has limited clinical value for tumor imaging.
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Objective To explore association between Helicobacter pylori (Hp) infection in oral cavity and gastric Hp infection through oral cavity and gastric Hp infection testing results analysis, and also to study the effect of Hp infection in oral cavity on Hp eradication treatment. Methods Through Hp saliva test (HPS) and 13C/14C urea breath test (UBT) method, the Hp in oral cavity and stomach were tested in 114 first-visit patients with upper gastrointestinal symptoms (group 1), 129 re-visiting patients who were diagnosed gastric Hp infection with eradication treatment for four weeks (group 2) and 33 volunteers without gastrointestinal symptoms. Results The positive rates of Hp infection by HPS method were 77.19%, 75.97% and 81.82% in group 1, group 2 and group 3 respectively. There was no significant difference between these three groups (χ2=0.47, P>0.05). The positive rate of Hp infection by UBT method in group 1 (52.63%) was higher than those of group 2 (34.11%) and group 3 (21.21%). Compared group 1 with group 2 or group 3, there was significant difference (χ2=8.848, 10.19, P0.05). In positive individuals of these three groups tested by UBT method, there was no significant difference of positive rate tested by HPS method (81.67%, 88.64% and 100% of three groups respectively, χ2=2.25, P>0.05). Conclusions The High detection of Hp antigen in saliva indicates that the oral cavity may be the second settlement of Hp beside stomach. The oral medicine haslittle effect on oral cavity Hp infection. The existence of oral Hp may be an important and direct factor of incidence and recurrent of gastric diseases.
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Objective To establish an automatic synthesis method for 11C-carfentanil (CFN) as an novel opiate receptor radioligand and study its biodistribution in rats. Methods 11C-Triflate-CH3 was bubbled into 0.5 mg precursor desmethyl-CFN (which was dissolved in 0.15 ml DMSO) to generate 11C-CFN in a V-tube at room temperature. Sep-Pak C2 column was used for purification of 11C-CFN, which was eluted by 3ml binary system aqueous solution, 10 ml water thrice, and then I ml ethanol. The biodistribution (% ID/g) of 11C-CFN in SD rats was studied. SPSS 13.0 was used for statistical analysis. Non-normal distribution data were analyzed using nonparametric test. Results The synthesis time for 11C-CFN was 20 min (end of bombardment, EOB). The synthesis yield was (35.5 ± 2.2) % on average (n = 12, uncorrected)with the radiochemical purity over 98%. Biodistribution study in rats showed that the tracer had a high brain uptake, rapid blood clearance, and a metabolic pathway via liver and kidney. The highest tracer uptake was in thalamus (4.26 ± 0.89) % ID/g and striatum (4.05 ± 1.08) % ID/g at 5 min after injection, followed by cerebral cortex (2.63±0.89) %ID/g, pons (2.26 ±0.57) % ID/g, hippocampus (2. 17 ±0.55) %ID/g and cerebellum (2. 15 ±0.39) %ID/g. Conclusions The automatic synthesis of 11C-CFN is fast and reliable, and this radioligand can be used for opiate receptor imaging.
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Objective HupA is one of the potential drugs which can be used to treat Alzheimer's disease(AD).The aim of this study was to explore the pharmacokinetics and biodistribution of HupA in vivo by using 11C-HupA.Methods A total of 25 SD rats were studied.They were divided into 5 groups (5 rats in each group).All had intravenous injection of 22 MBq(in0.2 ml)11C-HupA through tail vein.Dynamic im-aging Was acquired from 5 to 90 minutes after injection.Venous blood and organ activities were collected at 5,15,30,60.and 90 minutes after injection.Percentage activity of injected dose per gram of tissue(%ID/g)was calculated to characterize the biodistribution of tracer in different brain regions: frontal,apical, temporal,occipital,cerebellum,hippocampus,striatum,thalamencephalon, and brain stem, Variance analysis using SPSS 11.5 software was performed and compared among the study groups.Results 11C-HupA was character-istic for its quick clearance from blood,with half time T1/2 of (14.61±1.77) min,and clearance rate (CL)macokinetics of 11C-HupA in rats corresponded to a one-compartment model.with an activity curve(area 11C-HupA distribution in different brain regions,being greater in cerebral cortex,hippocampus,hypothala-mus and brain stem. Conclusions Pharmacokinetic study of 11C-HupA in brain was fast.convenient and showed high specificity and sensitivity.Its ability to quantitatively evaluate brain function and its character-istic distribution in mice provided some evidence for monitoring therapy in AD patients.