新型心肌灌注显像剂^99mTc—Q3的临床前药理研究

为了给临床应用研究提供依据,作者对新型心肌灌注显像剂＾９９ｍＴｃ－Ｎ,Ｎ’－亚乙基－二（乙酰丙酮亚胺）二「三（３－甲氧基－１－丙基）膦」（＾９９ｍＴｃ－Ｑ３）进行了临床前药理研究。其内容包括：＾９９ｍＴｃ－Ｑ３在兔体内的血药清除动力学 浆蛋白结合率,小鼠体内分布,家犬显像及异常毒性试验等。     

肾显像剂^99mTc—PAHIDA的实验研究

经＾９９ｍＴｃ－ＰＡＨＩＤＡ小鼠体内分布实验及家兔动态显像证明，肾脏积聚量远大于其它脏器，而且经尿流迅速排出。与现用的肾功能显像剂＾１３１Ｉ－ＯＩＨ相比，＾９９ｍＴｃ－ＰＡＨＩＤＡ有可能代替＾１３１Ｉ－ＯＩＨ进行肾功能测定。     

^99mTc核素心肌灌注显像的临床应用及评价

９９ｍＴｃ核素心肌灌注显像的临床应用及评价任利群郭力军王万忠马谭元（内蒙古自治区医院０１００１７）随着核医学的飞速发展，９９ｍＴｃ心肌灌注显像已成为诊断冠心病心肌梗塞，评价心肌梗塞预后的一种无创性手段。我院对５０例心肌梗塞（ＭＩ）患者的核素心肌灌注平...     

^99mTc—MIBI心肌断层显像心肌展开图显示法的应用

研究＾９９ｍＴｃ－ＭＩＢＩ心肌断层显像心肌展开图显示法的应用。方法；对２６例正常人，１１８例冠心病，其中心肌缺血９２例，心肌梗塞２６例进行＾９９ｍＴｃ－ＭＩＢＩ心肌断层显像，用一种新的半定量显示方法－心肌展开图显示法进行分析测定，并与心肌断层一般显示法进行了比较。     

^99mTc—MIBI心肌灌注断层显像监测蒽环类药物的心脏毒性

目的：探讨^99mTc—MIBI心肌灌注断层显像在蒽环类药物心脏毒性监测中的价值。方法：23例接受蒽环类药物治疗的患者，在治疗前进行心电图、心肌酶学检查、核素心室造影测左室射血分数(LVEF)和^99mTc—MIBI心肌灌注断层显像并计算相对定量值。并于每一周期治疗后重复上述检查。结果：蒽环类药物治疗一周期后，23例患者心肌相对定量值明显下降(P＜0．01)。其中11例吡喃阿霉素、6例表阿霉素和6例米托蒽醌治疗的患者，心肌相对定量值明显下降(P＜0．05)，心电图和心肌酶学无明显变化(P＞0．05)。蒽环类药物治疗多周期后的10例患者心肌相对定量值较治疗前下降(P＜0．05)。9例患者的心肌相对定量值(最大累积剂量为200mg／m^2)与一周期后无明显差别(P＞0．05)。10例患者治疗前及多周期治疗后LVEF均＞60％，又化疗前后无明显差别(P＞0．05).结论：^99mTc—MIBI心肌灌注断层显像能监测蒽环类药物所致的心肌损害，且较左室射血分数敏感，比心电图和心肌酶学检查优越，有利于指导蒽环类药物的临床应用。     

^99mTc—Q3和^201TI在不同流量冠脉灌注的离体兔心肌中摄取特性的对照研究

OBJECTIVE: This experiment was designed to explore myocardial 99mTc-Q3 uptake property. METHODS: 20 New Zealand White rabbit heart perfusion models were prepared and the isolated rabbit hearts were perfused by double-radionuclide method at varying coronary flow rates from 0.52 to 3.75 ml/g wet wt/min using developed perfusion liquid with autoblood in comparison with 201Tl in the absence of tracers recirculation. RESULTS: Mean 99mTc-Q3 peak instantaneous uptake was lower(0.65 +/- 0.077) and more affected by low rates (P < 0.05) than 201Tl peak instantaneous uptake (0.82 +/- 0.07, P < 0.01). CONCLSUION: These data were interpreted to indicate: 1. 99mTc-Q3 is not as well extracted as 201Tl; 2. varying the coronary flow rate has significant effects on the uptake of 99mTc-Q3 and 201Tl; 3. similarly to 201Tl, the coronary blood flow conditions may be overestimated by the myocardial radioactive uptake acquired with low flow perfusion, but the coronary blood flow conditions may be underestimated by the myocardial radioactive uptake acquired with high flow perfusion. Further studies on retention and clearance of 99mTc-Q3 need to be conducted.     

新型心肌灌注显像剂99mTc-Q3的标记方法学研究

为获得高质量的心肌灌注显像剂,作者进行了99m Tc-N,N′-亚乙基-二(乙酰丙酮亚胺)二[三(3-甲氧基-1-丙基)膦](99m Tc-Q3)的制备方法学研究.采用多元正交试验法进行了制备99mTc-Q 3最佳配方的筛选;用氯化亚锡化学还原法制备99mTC-Q3;用柱沉析法进行99m TC-Q3的分离和纯化、质量控制及体外稳定性试验;完成了无菌、热原、安全试验及家兔显像验证.制备99mTC-Q3的最佳配方为"A2B2C2"( 即:氢氧化钾、Sn2+及配体分别处于二水平的结果).药物标记率和放化纯大于99%.药物体外稳定性好,标记后4小时测得其标记率仍然大于92%(92%～99.37%).兔显像发现:注射 99 mTC-Q3后5分钟心肌便显影,至3小时心肌影像仍清晰可见.注射1小时后,血、肺中的放射性接近本底.提示:该方法可获得高质量的99mTC-Q3,而且为所有 9 9mTC-显像剂的制备建立了标准化流程,在此基础上可进一步研制99mTc-Q 3的一步法药盒.     

99mTc-MIBI myocardial perfusion imaging in patients with diabetes]

Seventy-four patients with diabetes were taken on both stress and rest 99m-Tc-MIBI SPECT imaging: 44 patients (59.5%) were found having myocardial ischemic disorders, including 28 cases of myocardial ischemia, 7 cases of myocardial infarction and 9 cases of both conditions. 113 segments were involved and 46% were located in the posterior and inferior walls, indicating that the right coronary artery is most susceptive to ischemia. Diabetic patients complicated hypertension and/or hyperlipidemia were at higher risk of either early occurrence of coronary disease. 99mTc-MIBI SPECT imaging is helpful in early diagnosis and therefore is significant in directing.     

99Tcm-MPO用于早期心肌灌注显像的动物实验研究

目的 :制备99mTc-2-巯基吡啶N-氧化物-N-乙氧基乙基-N,N-二[2-(二(3-甲氧基丙基)膦)乙基]胺([99mTcN(MPO)(PNP5)]+,简称99Tcm-MPO),考察其体内生物分布及其作为新型心肌灌注示踪剂的应用价值。方法 :二步法合成99TcmMPO,采用高效液相色谱仪(HPLC)分析其标记率及体外稳定性,鼠尾静脉注射99Tcm-MPO(3.7 MBq)后不同时间进行生物学分布研究,新西兰兔耳缘静脉注射99Tcm-MPO后行单光子发射断层扫描(SPECT)平面序列显像,以99Tcm-替曲膦(37 MBq)和99Tcm-甲氧基异丁基异腈(99Tcm-MIBI,37 MBq)为对照组;实验小型猪冠状动脉左回旋支(LCX)球囊血流阻断后,静脉注射99Tcm-MPO后15、60 min分别行心脏灌注显像(MPI)显像。结果:99Tcm-MPO标记率为(98.8±1.0)%,体外放置12 h放化纯为(96.5±0.8)%。体内生物分布显示:5 min时,99Tcm-MPO肾脏摄取与99Tcm-替曲膦类似,均低于99Tcm-MIBI,99Tcm-MPO肝脏摄取为(30.38±0.43)%ID/g,略高于99Tcm-MIBI和99Tcm-替曲膦,但99Tcm-MPO肝脏排泄快,15 min时99Tcm-MPO心脏摄取(9.38±0.70)%ID/g略低于99Tcm-MIBI,但差异无统计学意义,而99Tcm-MPO心/肝比值(2.21±0.44)明显高于99Tcm-MIBI(0.62±0.02)和99Tcm-替曲膦(0.89±0.06,F=22.29,P=0.016);静脉注射99Tcm-MPO后5 min兔平面显像可见心、肝清晰显影,15 min肝脏放射性摄取显著降低,心/肝比值为(0.85±0.32),高于99Tcm-MIBI(0.71±0.15)和99Tcm-替曲膦(0.59±0.64),差异无统计学意义。猪心肌缺血模型SPECT/CT显像示注射后15 min外侧壁心肌可见99Tcm-MPO明显放射性缺损区,心/肝比值与60 min差异无统计学意义。结论:99Tcm-MPO作为新型心肌显像剂,心脏摄取多,肝脏清除快,15 min心/肝放射性摄取高于99Tcm-MIBI和99Tcm-替曲膦,预期可用于早期心肌灌注显像,具有良好的临床应用前景。     

^99Tc^m—MIBI心肌灌注显像对心肌桥患者心脏功能评价的临床研究

目的以CT冠状动脉血管成像（CTA）为对比,探讨^99Tc^m-MIBI心肌灌注显像对心肌桥患者心脏功能评价的临床研究。方法回顾性分析42例（心肌桥患者31例,正常人11例）接受^99Tc^m-MIBI心肌灌注显像及冠脉CTA检查的住院患者,全部患者行静息心肌灌注显像,18例行负荷心肌灌注显像,我们对纳入对象进行对比研究。结果静息心肌灌注显像发现心肌桥心肌缺血性改变15例,阳性检出率为51．61％（16／31）;运动负荷心肌灌注显像发现心肌缺血7例,阳性检出率为38．89％（7／18）,心肌桥患者与正常对照组静息心肌灌注显像心肌缺血性改变的阳性检出率差异无统计学意义（P〉0．05）。静息心肌灌注显像与心电图对心肌桥心肌缺血的诊断呈正相关（P〈0．05,r=0．369）。静息心肌灌注显像射血分数在心肌桥组与正常对照组差异有统计学意义（P〈0．05）。结论与其他检查手段相比,门控静息或运动负荷心肌灌注显像可以发现心肌桥所导致的心肌缺血性改变,并为心肌桥患者心脏功能的评价提供有临床应用价值的信息。     

新型心肌灌注显像剂99mTc-Q3的临床前药理研究

为了给临床应用研究提供依据 ,作者对新型心肌灌注显像剂 99m Tc- N,N′-亚乙基 -二 (乙酰丙酮亚胺 )二〔三 (3-甲氧基 - 1 -丙基 )膦〕(99m Tc- Q3)进行了临床前药理研究。其内容包括 :99m Tc- Q3在兔体内的血药清除动力学、血浆蛋白结合率、小鼠体内分布、家犬显像及异常毒性试验等。结果显示 :1 9m Tc- Q3的放化纯度 >99% ,室温下放置 6小时稳定 ;2兔血药清除动力学符合一次静脉给药的药代动力学二室模型 ;3小鼠体内分布显示 99m Tc- Q3在小鼠心肌摄取早 ,摄取值高 ,且放射性滞留时间长 ,血、肺及肝药物清除均快 ;4从家犬显像可见 ,99m Tc- Q3在肺中清除迅速 ,1小时后肺部放射性水平接近本底 ,1 5分钟时心肌影像已清晰可见 ,3小时后才逐渐消退 ;5 99m Tc- Q3的兔血浆蛋白结合率低 (7.1 3± 0 .42 % ) ;6小鼠对药物的耐受剂量为人的 5 0 0倍。上述结果表明 ,99m Tc- Q3的体外性质稳定 ,心肌摄取早 ,摄取率高 ,且放射性滞留时间长 ,血、肺及肝清除快 ,安全 ,具有临床研究价值     

^99mTc-N-NOET运动心肌灌注显像诊断冠状动脉疾病

OBJECTIVE: To investigate the value of (99m)Tc-N-NOET(NOET) myocardial perfusion imaging during exercise in the diagnosis of coronary artery disease (CAD), and the relationship between exercise NOET lung/heart ratio and left ventricular diastolic function. METHODS: Exercise-delayed NOET myocardial perfusion imaging was performed in 49 patients undergoing coronary angiography, among whom 29 had coronary stenosis>or=50% and 20 normal coronary artery. RESULTS: The sensitivity and specificity of exercise NOET myocardial perfusion imaging were 86.2% and 95.0%, respectively, in the detection of CAD. The NOET lung/heart ratio of CAD patients with multiple branch involvement (0.76+/-0.13) was significantly higher than those of patients with single branch lesion (0.62+/-0.06) and with normal coronary artery (0.58+/-0.13, F=18.04, P=0.002- 0.001). When the lung/heart ratio was over 0.70, the sensitivity and specificity of the imaging for detecting the presence of multiple branch involvement were 93.5% and 83.3%, respectively. NOET lung/heart ratio showed a significant correlation with E/A ratio (r=-0.771, P<0.000 1). CONCLUSION: Exercise NOET lung/heart ratios has diagnostic values for multiple branch lesions and left ventricular diastolic function abnormalities in patients with CAD.     

A study of glycogen storage disease with 99Tcm-MIBI gated myocardial perfusion imaging

Objective

Gated myocardial perfusion imaging (G-MPI) is regularly performed using single-photon emission computed tomography. The objective of this study was to evaluate the clinical value of 99Tcm-methoxyisobutylisonitrile (MIBI) myocardial imaging in glycogen storage disease (GSD).

Methods

99Tcm-MIBI G-MPI was performed in nine patients with clinically proven GSD. QGS quantitative software was used for processing and interpretation. Left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were automatically generated. The myocardium was divided into seven segments, 20 sub-segments and a five-point scoring system was used.

Results

Seven out of nine cases were abnormal and the positive rate of G-MPI was 77.8 %. Sixty-two sub-segments of injured myocardium were detected in 140 sub-segments of seven abnormal patients. One injured segment was observed in one patient (14.3 %), two segments were detected in two patients (28.6 %) and three or more abnormal segments were observed in four patients (57.1 %).

Conclusion

99Tcm-MIBI G-MPI can detect myocardial damage in GSD as a non-invasive method. It plays an important role in the clinic.     

99mTc-Q3和201Tl在不同流量冠脉灌注的离体兔心肌中摄取特性的对照研究

目的　进一步探讨心肌对 99m Tc- Q3 的摄取特性。方法　制备离体兔心脏灌注模型 ,采用双核素法 ,用含兔自体血红细胞的改良灌注液进行离体兔心脏灌注 ,研究 99m Tc- Q3 和 2 0 1 Tl在不同流量 (每分钟 0 .5 2～3.75 m l/g湿心肌组织 )冠脉灌注离体兔心肌中的摄取特性。结果　心肌对 99m Tc- Q3 的平均瞬时高峰摄取值 ( 0 .6 5±0 .0 77)低于 2 0 1 Tl值 ( 0 .82± 0 .0 7,P<0 .0 0 1) ,且前者受灌注流量的影响比后者更明显 ( P<0 .0 5 )。结论　 99m Tc- Q3的心肌摄取值比 2 0 1 Tl低 ;改变灌注流量对 99m Tc- Q3 和 2 0 1 Tl的心肌摄取值都有显著影响 ;与 2 0 1 Tl相同 ,低灌注流量水平获得的心肌对 99m Tc- Q3 的摄取值可能会过高估计心脏血流量 ,而高灌注流量水平获得的心肌对 99m Tc- Q3 的摄取值可能会过低估计心脏血流量