住友CLC模块在线优化合成^13N-NH3· H2O的研究

目的 确定住友HM-10回旋加速器相关参数,小步优化住友CLC模块,合成显像良好的^13N-NH3· H2O.方法 优化住友HM-10回旋加速器的束流大小、轰靶时间和靶水中乙醇去自由基含量,提高化学反应效率.用阳离子交换柱（CM柱）吸附靶水和小步优化纯化流程得到高化学纯度的^13N-NH3·H2O,并实现一根CM柱上多次吸附纯化（3次左右）.结果 用30 μA束流轰击10 mmol/L乙醇11 min,合成^13N-NH3·H2O 27批次,产量为925 MBq左右,放化纯度和化学纯度均大于99％,注射大狗后心肌灌注显像良好.结论 经过回旋加速器锂靶反应条件的优化和住友CLC纯化模块的小步改进能得到产量稳定、显像良好的^13N-NH3· H2O,能够满足实验及临床要求.     

腺苷负荷13N-NH3 PET心肌灌注显像结合冠状动脉CTA诊断冠心病

目的 评价腺苷负荷13N-NH3PET心肌灌注显像(MPI)与CT冠状动脉造影(CTA)相结合对提高冠心病(CAD)诊断准确性的临床应用价值.方法 对25例怀疑CAD的患者同时行腺苷负荷13N-NH3MPI及CTA,1个月内行导管法冠状动脉造影(CAG).结果 (1)25例患者共300个冠状动脉节段,CTA显示良好节段为263个,显示率(显示良好节段所占百分比)达87.7%.(2)25例患者CTA、MPI及CTA+MPI诊断CAD的灵敏度、特异性、准确性、阳性预测值及阴性预测值分别为82.1%(23/28),87.5%(14/16)及93.8%(15/16);93.2%(219/235),8/9及9/9;92.O%(242/263),88.0%(22/25)及96.0%(24/25);58.9%(23/29),93.3%(14/15)及100.0%(15/15);97.8%(219/224),8/10及9/10.结论 PET/CT实现了同机腺苷负荷"N-NH3PET心肌灌注显像与CTA相结合,提高了诊断CAD的准确性.     

13N-NH3 PET显像评价18F-FDG PET示低代谢脑内病变的应用价值

目的 探讨13N-NH3 PET显像在18F-FDG PET显像呈低代谢表现的脑内病变中的应用价值.方法 对18例18F-FDG PET显像呈低代谢表现的脑内病变患者[男13例,女5例,年龄20～68(42.4±12.6)岁]进行13N-NH3PET显像前瞻性研究.2种显像间隔时间在10 d内,间隔时间内患者未接受任何治疗.18例患者中,初诊14例,星形细胞瘤治疗后复诊患者4例;最后经病理(13例)、临床随访(5例)证实有神经胶质瘤10例,肺癌脑转移1例,胚胎发育不良性神经上皮瘤(DNT)1例和非肿瘤性病变6例(3例放射性坏死,2例脑炎,l例脑缺血病变).采用对称ROI法计算2种显像肿瘤与对侧正常脑组织放射性比值(T/C).计算13N-NH3 PET诊断效能.应用SPSS 13.0软件对13N-NH3和18F-FDG的T/C行配对t检验,对肿瘤性病变与非肿瘤性病变中13N-NH3的T/C行两样本t检验.结果 12例肿瘤性病变中,7例表现为13N-NH3摄取增高(星形细胞瘤5例,胶质母细胞瘤2例),诊断灵敏度为58％ (7/12);3例低级别的胶质瘤、1例转移瘤及1例DNT表现为13N-NH3摄取减低.在肿瘤性病变中,13N-NH3的T/C明显高于18F-FDG(1.24±0.66和0.67±0.24,t=-3.740,P＜0.05).6例非肿瘤性病变均表现为13N-NH3摄取减低,特异性为6/6.在非肿瘤性病变中,18F-FDG和13N-NH3的T/C分别为0.68 ±0.15和0.70±0.19,两者间差异无统计学意义(t=-0.246,P＞0.05).肿瘤性病变的13N-NH3T/C明显高于非肿瘤性病变(1.24±0.53和0.70 ±0.19,t=2.624,P＜0.05).结论 在18F-FDG PET显像呈低代谢的脑内病变(尤其是星形细胞瘤)的诊断与鉴别诊断中,13 N-NH3 PET显像具有很高的特异性,但其灵敏度有待进一步提高.     

S-11C-甲基-L-半胱氨酸在荷Hepa 1-6肝癌小鼠体内的分布及PET显像研究

目的 研究S-11C-甲基-L-半胱氨酸(11C-MCYS)在荷Hepa 1-6肝癌小鼠体内的生物学分布及其在肿瘤PET显像中的价值.方法 (1)荷Hepa 1-6肝癌小鼠25只,经尾静脉注射11C-MCYS注射液1.48 MBq,分别在注药后5、10、20、30和60 min5个时间点测量肿瘤组织及各器官的放射性,计算％ID/g.荷瘤小鼠10只,经尾静脉注射11C-MCYS 1.48 MBq,分别于5、10、20、30和60 min行全身PET/CT扫描,观察全身放射性分布及代谢情况.(2)荷瘤小鼠及炎性反应小鼠模型各20只,经尾静脉注射11C-MCYS 1.48 MBq,1h后行全身PET/CT扫描.通过ROI获得肿瘤和炎性反应组织的SUVmax,并计算肿瘤/肌肉、炎性反应组织/肌肉放射性比值.采用t检验进行统计分析.结果 (1)11C-MCYS在体内吸收迅速,给药后5 min放射性分布即可达到高峰,5 min时肝和肾放射性分布分别为(1.97±0.12)和(1.02±0.09) ％ID/g,60 min时肝和肾放射性摄取降为(0.53±0.14)和(0.29±0.05)％ID/g,而脑、肺、胃及肌肉等组织放射性摄取均小于(0.23±0.05)％ID/g,肿瘤组织放射性摄取为(0.48±0.05)％ID/g.荷瘤小鼠不同时间点PET显像示小鼠各脏器的放射性摄取与各相应时间点小鼠体内放射性分布一致.(2)肿瘤组织摄取11C-MCYS较高,SUVmax为4.58±0.65,而炎性反应组织摄取11C-MCYS较低,SUVmax为1.02±0.18,肿瘤/肌肉及炎性反应组织/肌肉的放射性比值分别为7.27和1.62,差异有统计学意义(t=2.906,P＜0.01).结论 11C-MCYS是一种有前景的新型氨基酸类PET显像剂,有望用于肿瘤与无菌性炎性反应的鉴别.     

基于人工免疫网络的小动物PET分子影像动力学参数估计方法

目的基于人工免疫网络提出无需设定初值的示踪剂动力学模型参数估计算法,以提高PET分子影像动力学模型分析方法的可靠性。方法对18F—FDG小鼠PET显像实验中有关数据,用ROI技术获取肝和左心室示踪剂的时间一放射性曲线（TAC）,同时经小鼠尾静脉多点采血获取尾静脉血TAC。对动物实验数据进行示踪剂药代动力学建模,设计人工免疫网络算法估计模型参数,并计算小鼠肝葡萄糖代谢率参数Ki。结果获得肝、左心室和尾静脉血TAC。对小动物实验数据建模,应用基于人工免疫网络的药代动力学参数优化方法（PKAIN）求解模型参数,实现无需设定初始值的模型参数估计,并计算3只小鼠K值,平均值分别为0．0024,0．0417和0．0047。PKAIN算法求出对输出模型参数估计的最大加权残差平方和的平均值小于0．0745,标准差最大为0．0084,表明能够获得准确稳定的模型参数。结论人工免疫网络智能计算方法可提高PET分子影像动力学建模方法的可靠性、实用性提供了新型的智能信息处理技术。     

阿尔茨海默病18F-FDDNP PET显像初步临床应用

目的 探讨2-(1-{6-[(2-18F-乙基)(甲基)氨]-2-萘}-乙叉)-丙二腈(18F-FDDNP)PET显像条件及用于阿尔茨海默病(AD)诊断的价值.方法 7例AD(AD组),6例血管性痴呆(VD组)患者及6名智力正常老年对照者(HC组).静脉注射18F-FDDNP后HC组中的3例采用连续动态采集程序扫描并生成时间-放射性曲线,余受试者在药物注射后5,25和45 min分别采集图像.采用ROI法进行图像分析,计算3组受试者各脑区在5～25 min及5～45 min的放射性清除率并进行统计分析.结果 18F-FDDNP能快速通过血脑屏障且之后能很快从健康脑组织中洗脱.AD患者脑内放射性清除较HC组慢,而VD患者PET显像与HC组差别不大.AD组大脑皮质及皮质下核团放射性清除率与HC组比较,差异有统计学意义(P＜0.05),而白质和小脑差异无统计学意义.VD患者与HC组比较,除纹状体外各脑区放射性清除率差别无统计学意义.结论 18F-FDDNP符合神经系统显像剂的要求.18F-FDDNP PET脑显像能有效诊断AD,且可以鉴别AD和VD.     

小动物SPECT的应用和进展

小动物SPECT是实验科学向临床科学过渡的重要工具,已广泛应用在临床前新药研发、人类生理和疾病实验动物模型的研究中.随着硬件技术和图像重建算法的进展,小动物SPECT的系统灵敏度、空间分辨率和定量准确性都得到了明显提高.与小动物PET相比,小动物SPECT在研究的适应性、放射性药物来源的便利性及研究成本上具有更大优势,在一段时间内仍将是疾病临床前分子影像研究的重要手段之一.     

胃癌PET-CT显像的临床应用

目的：评价^18F-脱氧葡萄糖（FDG）PET-CT显像在胃癌诊断中的价值。方法：26例临床可疑胃癌及胃癌术后吻合口复发患者（男20例，女6例，年龄48～82岁）行全身^18F-FDG PET-CT扫描。患者于左手臂静脉注入^18F-FDG前行胃肠道喝水低张准备，患者行^18F-FDG PET-CT扫描前再次喝水充盈胃肠道。图像有2位核医学医师及2位影像学医师共同阅片。结果与病理结果及临床随访结果相对照。结果：^18F-FDG PET-CT扫描可同时得到PET、CT及PET-CT图像。PET图像发现病灶19例，PET-CT图像发现病灶20例，病理结果及临床随访结果证实原发性胃癌16例，胃癌术后吻合口复发3例，胃癌术后改变3例，胃炎4例。PET图像诊断胃癌及胃癌术后吻合口复发的灵敏性为89％，特异性为71％，准确性为85％，阳性预测值为89％，阴性预测值为71％；PET-CT图像诊断胃癌及胃癌术后吻合口复发的灵敏性为100％，特异性为86％，准确性为96％，阳性预测值为95％，阴性预测值为100％。结论：PET-CT在诊断胃癌及胃癌吻合口复发方面优越于PET图像。     

201Tl与13N-NH3、18F-FDG PET心肌显像判断存活心肌的对比研究

目的　比较再注射2 0 1T1心肌显像与联合应用13 N NH3 及18F 脱氧葡萄糖 (FDG)心肌PET显像判断存活心肌的临床价值。方法　 2 0例心肌梗死患者 ,行2 0 1T1SPECT负荷、再分布、再注射显像及13 N NH3 、18F FDGPET心肌显像。将左室分成 9个节段 ,以视觉评价法对放射性分布进行 4级评分。获得2 0 1T1SPECT再分布、再注射像及18F FDGPET显像的局部心肌摄取率 (%ID)。结果　PET判定为存活心肌的 48个节段中 ,45个节段 (93.8% ) 2 0 1T1再注射像也判定为存活心肌。在2 0 1T1再分布像示放射性分布严重低下的 2 4个节段 ,2 0 1T1再注射像与PET显像判定存活心肌的一致率为 87.5 % ,其中 37.5 %为存活心肌节段 ,5 0 %为无存活心肌节段。 2种显像方法的 %ID无明显差异 ,且呈显著正相关 (r=0 .72 2 )。结论　再注射2 0 1T1心肌显像判断存活心肌的准确性与PET心肌显像相似 ,有较大的临床应用价值。     

99Tcm-3PRGD2 SPECT/CT分子影像在乳腺癌诊疗中的应用进展

乳腺癌是女性发病率最高的恶性肿瘤。99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体（99Tcm-3PRGD₂）是近年来人工合成的可用于乳腺癌分子显像的一种SPECT示踪剂。99Tcm-3PRGD₂ SPECT/CT可用于早期诊断乳腺癌并进行准确的分期及分子分型,据此进行诊疗方案的选择,有助于降低患者的病死率,并提高患者的生活质量。笔者就99Tcm-3PRGD₂ SPECT/CT在乳腺癌诊疗过程中的应用进展进行综述,并作出展望。     

Dynamic 13N-ammonia PET: a new imaging method to diagnose hypopituitarism.

We have developed a new imaging method to evaluate the blood perfusion and ammonia metabolism of the pituitary gland, and we preliminarily assessed its role in the diagnosis of hypopituitarism. METHODS: Six female healthy volunteers (age range, 20-46 y) and 6 female patients (age range, 23-42 y) were enrolled in this study. Dynamic (13)N-NH(3) PET was performed. Time-activity curves for the pituitary gland and internal carotid artery were generated by setting regions of interest on the transverse planes of the pituitary gland. The standardized uptake value of the pituitary gland, the radioactive ratio of pituitary to thalamus (P/T), and the first-pass uptake rate of ammonia in the pituitary gland were calculated. RESULTS: (13)N-Ammonia was extracted rapidly by pituitary tissue in the first 120 s after injection and trapped in pituitary tissue in the healthy volunteers. Three to 20 min after injection, the pituitary gland was clearly seen in the healthy volunteers, and the mean (+/-SD) size of the pituitary gland on (13)N-ammonia PET images was (1.09 +/- 0.17 cm) x (1.08 +/- 0.14 cm) x (1.12 +/- 0.09 cm). However, in patients with hypopituitarism, the first-pass uptake rate of ammonia in the pituitary gland was significantly lower than that in healthy volunteers (0.35 +/- 0.10 vs. 0.75 +/- 0.07). On images of patients, the pituitary gland was absent or could not clearly be found, was small or malformed, and showed significantly lower uptake of (13)N-NH(3) than in healthy volunteers (standardized uptake value, 1.15 +/- 0.34 vs. 3.74 +/- 1.44; P/T, 0.65 +/- 0.23 vs. 1.24 +/- 0.34). CONCLUSION: Dynamic (13)N-ammonia PET can provide information on blood perfusion and metabolism of the pituitary gland and is useful in early monitoring of damage to the pituitary gland and in diagnosing hypopituitarism.     

Characterizing the normal range of myocardial blood flow with 82rubidium and 13N-ammonia PET imaging

Background

Diagnosis of coronary disease and microvascular dysfunction may be improved by comparing myocardial perfusion scans with a database defining the lower limit of normal myocardial blood flow and flow reserve (MFR). To maximize disease detection sensitivity, a small normal range is desirable. Both ¹³N-ammonia and ⁸²Rb tracers are used to quantify blood flow and MFR using positron emission tomography (PET). The goal of this study was to investigate the trade-off between noise and accuracy in both ⁸²Rb and ¹³N-ammonia normal databases formed using a net retention model.

Methods

Fourteen subjects with <5% risk of CAD underwent rest and stress ⁸²Rb and ¹³N-ammonia dynamic PET imaging in a randomized order within 2 weeks. Myocardial blood flow was quantified using a one-compartment model for ⁸²Rb, and a two-compartment model for ¹³N-ammonia. A simplified model was used to estimate tracer retention, with tracer-specific net extraction functions derived to obtain flow estimates.

Results

Normal variability of retention reserve was equivalent for both tracers (±15% globally, ±16% regionally) and was lower in comparison to compartment model results (P < .05). The two-compartment model for ¹³N-ammonia had the smallest normal range of global blood flow resulting in a lower limit of normal MFR = 2.2 (mean ? 2 SD).

Conclusion

These results suggest that the retention model may have higher sensitivity for detection and localization of abnormal flow and MFR using ⁸²Rb and ¹³N-ammonia, whereas the ¹³N-ammonia two-compartment model has higher precision for absolute flow quantification.     

13N-NH3 PET脑血流灌注显像诊断缺血性脑血管病变

目的探讨13N-NH3 PET脑血流灌注显像对缺血性脑血管病变的诊断价值.方法对5例健康志愿者,20例缺血性脑血管病变患者静脉注射13N-NH3 740～925 MBq,3～5 min后行T+E 二维方式脑血流灌注显像.图像分析采用视图分析和脑皮质标准摄取值(SUV)半定量分析,镜像比值法测量左/右两侧相应脑区SUV比值(SUV_r).其中9例短暂性脑缺血发作(TIA)行乙酰唑胺(ACZ)脑负荷试验,观察口服ACZ前后脑区影像、SUV和SUV_r变化.结果正常左/右脑区平均SUV_r为0.99±0.15,患侧/健侧(L/N)比值<0.85为稀疏区,<0.7为缺损区.13例TIA 13 N-NH3 PET显像示7例阳性,8例行MRI 2例阳性,6例行CT 1例阳性.7例TIA13N-NH3 PET显像阳性患者发现29个缺血灶,平均SUV 1.78±0.41,低于对照组(2.51±0.52,t=8.78,P<0.05).脑梗死(CI)患者共发现13个梗死灶,平均SUV 1.05±0.23,明显低于对照组和TIA组(t=5.9,P<0.001).9例ACZ脑负荷试验,缺血灶由静息29处增至35处,检出率提高17.1%;TIA阳性率由53.8%提高到62.5%;静息平均SUV_r为0.87±0.11,口服ACZ后减低至0.77±0.07(t=6.47,P<0.05).结论 13N-NH3PET脑灌注显像安全、无创伤性,灵敏度高且病灶定位准确.口服ACZ脑负荷试验安全、简便、可靠,对评价局部脑血流储备功能有重要价值.     

Coronary calcium score scans for attenuation correction of quantitative PET/CT 13N-ammonia myocardial perfusion imaging

Purpose  

The aim of this study was to evaluate whether ECG-triggered coronary calcium scoring (CCS) scans can be used for attenuation correction (AC) to quantify myocardial blood flow (MBF) and coronary flow reserve (CFR) assessed by PET/CT with ¹³N-ammonia.     

A fast nonlinear method for parametric imaging of myocardial perfusion by dynamic (13)N-ammonia PET.

A parametric image of myocardial perfusion (mL/min/g) is a quantitative image generated by fitting a tracer kinetic model to dynamic (13)N-ammonia PET data on a pixel-by-pixel basis. There are several methods for such parameter estimation problems, including weighted nonlinear regression (WNLR) and a fast linearizing method known as Patlak analysis. Previous work showed that sigmoidal networks can be used for parameter estimation of mono- and biexponential models. The method used in this study is a hybrid of WNLR and sigmoidal networks called nonlinear regression estimation (NRE). The purpose of the study is to compare NRE with WNLR and Patlak analysis for parametric imaging of perfusion in the canine heart by (13)N-ammonia PET. METHODS: A simulation study measured the statistical performance of NRE, WNLR, and Patlak analysis for a probabilistic model of time-activity curves. Four canine subjects were injected with 740 MBq (13)N-ammonia and scanned dynamically. Images were reconstructed with filtered backprojection and resliced into short-axis cuts. Parametric images of a single midventricular plane per subject were generated by NRE, WNLR, and Patlak analysis. Small regions of interest (ROIs) were drawn on each parametric image (8 ROIs per subject for a total of 32). RESULTS: For the simulation study, the median absolute value of the relative error for a perfusion value of 1.0 mL/min/g was 16.6% for NRE, 17.9% for WNLR, 19.5% for Patlak analysis, and 14.5% for an optimal WNLR method (computable by simulation only). All methods are unbiased conditioned on a wide range of perfusion values. For the canine studies, the least squares line fits comparing NRE (y) and Patlak analysis (z) with WNLR (x) for all 32 ROIs were y = 1.02x - 0.028 and z = 0.90x + 0.019, respectively. Both NRE and Patlak analysis generate 128 x 128 parametric images in seconds. CONCLUSION: The statistical performance of NRE is competitive with WNLR and superior to Patlak analysis for parametric imaging of myocardial perfusion. NRE is a fast nonlinear alternative to Patlak analysis and other fast linearizing methods for parametric imaging. NRE should be applicable to many other tracers and tracer kinetic models.     

Synthesis of S-[13N]nitrosoglutathione (13N-GSNO) as a new potential PET imaging agent

In the present paper, a fast and reproducible method for the synthesis of S-[¹³N]nitrosoglutathione is reported for the first time. The labeling strategy is based on the production of [¹³N]NO₃⁻ via the ¹⁶O(p,α)¹³N nuclear reaction in water, as opposed to the standardized production of [¹³N]NH₄⁺ in 2 mM aqueous ethanol. Following the reduction of [¹³N]NO₃⁻ to [¹³N]NO₂⁻, the reaction with glutathione in the presence of hydrochloric acid led to the desired radiotracer with a good radiochemical yield (24.2±2.0% end of synthesis, n=5) in a short production time (3 min from the end of bombardment).     

Evaluation of the endothelial function in hypertensive patients with 13N-ammonia PET

Background

Essential hypertension is one of the main risk factors for the development of coronary artery disease (CAD). Hypertension causes endothelial dysfunction which is considered an early sign for the development of CAD. Positron emission tomography is a non-invasive imaging technique that measures myocardial blood flow (MBF), allowing us to identify patients with endothelial dysfunction.

Methods and Results

19 patients without comorbidities recently diagnosed hypertensive, as well as 21 healthy volunteers were studied. A three-phase (rest, cold pressor test, and adenosine-induced hyperemia) ¹³N-ammonia PET was performed, and MBF was measured. Endothelial-Dependent Vasodilation Index, ??MBF, and coronary flow reserve (CFR) were calculated for each patient. Hypertensive patients had a significantly higher systolic and diastolic blood pressures compared with the control group (134.6?±?11.7/86.4?±?10.6?mm?Hg and 106.0?±?11.8/71.4?±?6.6?mm?Hg, respectively, P?<?.001). The ENDEVI (1.28?±?0.26 vs 1.79?±?0.30, P?<?.001), the ??MBF (0.81?±?0.50 vs 0.25?±?0.21, P?<?.001) and the CFR (2.18?±?0.88 vs 3.17?±?0.68, P?=?.001) were significantly lower in the hypertensive patients compared to the control group, 84% of the former group had endothelial dysfunction i.e., ENDEVI?<?1.5 and 58% had vasomotor abnormalities, i.e., CFR?<?2.5.

Conclusions

In this study, we showed that recently diagnosed hypertensive patients have coronary endothelial dysfunction and vasomotor disturbances which are early signs for the development of CAD.     

Clinical value of 13N-ammonia PET in assessment of cardiac disease: meta-analysis

The clinical value of 13N-ammonia PET is reviewed by using previously published articles with significant evidence level. This meta-analysis indicated that due to excellent myocardial blood flow images, 13N-ammonia PET permits better diagnostic accuracy of ischemic heart disease and viability assessment than myocardial perfusion SPECT. Furthermore, quantitative assessment of myocardial blood flow (MBF) in absolute units can be performed using 13N-ammonia PET. MBF measurement is a useful tool to evaluate cardiac pathophysiology and monitor therapeutic effects of cardiac disease and cardiovascular risk factors.