锝[^(99m)Tc]放射性药品注射用配套药盒中Sn(II)含量测定方法概述

氯化亚锡的含量是锝[^(99m)Tc]放射性药品注射用配套药盒质量控制的重要指标之一,直接影响锝[^(99m)Tc]放射性药品的临床使用效果,选择合适的分析方法对其进行准确测定至关重要。通过对比《中国药典》2020年版收录的放射性药品质量标准以及相关文献资料,对常用的氯化亚锡含量测定方法包括电位分析法、分光光度法、高效液相色谱法等的特点、测定原理以及应用进行分析总结,可为建立更科学、合理的锝[^(99m)Tc]放射性药品注射用配套药盒质量标准提供技术参考。

Direct technetium-99m labeling of anti-hepatoma monoclonal antibody fragment:a radioimmunoconjugate for hepatocellular carcinoma imaging

AIM To directly radiolabel an anti-hepatomamAb fragment HAb18 F（ab’）2 with 99mTc bystannous-reduced method,and assess thestability,biodistribution and radioimmun-oimaging（RⅡ）.METHODS Immunoreactive fraction wasdetermined according to Lindmo’s method.Ellman’s reagent was used to determine thenumber of thiols in the reduced F（ab’）2.Labelingefficiency and homogeneity were measured bypaper chromatography,sodium dodecylsulphatepolyacrylamide gel electrophoresis（SDS-PAGE）and autoradiography.Challenge assay involvedthe incubation of aliquots of labeled antibody inethylenediaminetetraacetate（ EDTA ）and L-cysteine（L-cys）solutions with different molarratio at 37℃ for 1h,respectively.Investigationsin vivo utilized nude mice bearing humanhepatocellular carcinoma（HHCC）xenograftswith gamma camera imaging and tissuebiodistribution studies at regular intervals.RESULTS The labeling procedure was finishedwithin 1.5 h compared with the'pretinning'method which would take at least 21h.In vitrostudies demonstrated that the radiolabeled mAbfragment was homogeneous and retained itsimmunoreactivity.Challenge studies indicatedthat 99mTc-labeled HAb18 F（ab’）2 in EDTA is morestable than in L-cys.Imaging and biodistribution showed a significant tumor uptake at 24 h post-injection of 99mTc-labeled HAb18 F（ab’）2.Theblood,kidney,liver and tumor uptakes at 24hwere 0.56±0.09,56.45±11.36,1.43±0.27 and6.57±3.01（%ID/g）,respectively.CONCLUSION 99mTc-HAb18 F（ab’）2 conjugateprepared by this direct method appears to be aneffective way to detect hepatoma in nude micemodel.

Leukocyte-technetium-99m uptake in Crohn's disease:Does it show subclinical disease?

AIM:To evaluate inflammatory activity in patients with Crohn's disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy.METHODS: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn's Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol and the scintigraphic images, including single photon emission computed tomography, were obtained 30 min and 2 h after injection of the radiolabeled leukocytes.RESULTS:The labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 55.0%±10%. Six of the 20 patients (30%) presented congruent results for the three parameters investigated (CDAI, Scintigraphic Index and CRP). On the other hand, 14 patients (70%) did not show congruent results. There was no significant correlation between the indices analyzed according to the Spearman test (P>0.05,n=20).CONCLUSION: The results suggest that 99mTc-HMPAO-labeled leukocyte scintigraphy could be important for determining inflammatory activity in CD even in the absence of clinical symptoms.

Technetium-99m-labeled annexin V imaging for detecting prosthetic joint infection in a rabbit model

Accurate and timely diagnosis of prosthetic joint infection is essential to initiate early treatment and achieve a favorable outcome. In this study, we used a rabbit model to assess the feasibility of technetium-99m-labeled annexin V for detecting prosthetic joint infection. Right knee arthroplasty was performed on 24 New Zealand rabbits. After surgery, methicillin-susceptible Staphylococcus aureus was intra-articularly injected to create a model of prosthetic joint infection （the infected group, n = 12）. Rabbits in the control group were injected with sterile saline （n= 12）. Seven and 21 days after surgery, technetium-99m-labeled annexin V imaging was per- formed in 6 rabbits of each group. Images were acquired 1 and 4 hours after injection of technetium-99m- labeled annexin V （150 MBq）. The operated-to-normal-knee activity ratios were calculated for quantitative ana- lysis. Seven days after surgery, increased technetium-99m-labeled annexin V uptake was observed in all cases. However, at 21 days a notable decrease was found in the control group, but not in the infected group. The operated-to-normal-knee activity ratios of the infected group were 1.84 ±0.29 in the early phase and 2.19 ±0.34 in the delay phase, both of which were significantly higher than those of the control group （P=0.03 and P=0.02）. The receiver operator characteristic curve analysis showed that the operated-to-normal-knee activity ratios of the delay phase at 21 days was the best indicator, with an accuracy of 80%. In conclusion, technetium- 99m-labeled annexin V imaging could effectively distinguish an infected prosthetic joint from an uninfected prosthetic joint in a rabbit model.

Technetium-99m-labeled macroaggregated albumin lung perfusion scan for diagnosis of hepatopulmonary syndrome: A prospective study comparing brain uptake and whole-body uptake

BACKGROUND Hepatopulmonary syndrome (HPS) is an arterial oxygenation defect induced by intrapulmonary vascular dilatation (IPVD) in the setting of liver disease and/or portal hypertension.This syndrome occurs most often in cirrhotic patients(4%-32%) and has been shown to be detrimental to functional status,quality of life,and survival.The diagnosis of HPS in the setting of liver disease and/or portal hypertension requires the demonstration of IPVD (i.e.,diffuse or localized abnormally dilated pulmonary capillaries and pulmonary and pleural arteriovenous communications) and arterial oxygenation defects,preferably by contrast-enhanced echocardiography and measurement of the alveolar-arterial oxygen gradient,respectively.AIM To compare brain and whole-body uptake of technetium for diagnosing HPS.METHODS Sixty-nine patients with chronic liver disease and/or portal hypertension were prospectively included.Brain uptake and whole-body uptake were calculated using the geometric mean of technetium counts in the brain and lungs and in the entire body and lungs,respectively.RESULTS Thirty-two (46%) patients had IPVD as detected by contrast-enhancedechocardiography.The demographics and clinical characteristics of the patients with and without IPVD were not significantly different with the exception of the creatinine level (0.71±0.18 mg/dL vs 0.83±0.23 mg/dL;P=0.041),alveolararterial oxygen gradient (23.2±13.3 mmHg vs 16.4±14.1 mmHg;P=0.043),and arterial partial pressure of oxygen (81.0±12.1 mmHg vs 90.1±12.8 mmHg;P=0.004).Whole-body uptake was significantly higher in patients with IPVD than in patients without IPVD (48.0%±6.1%vs 40.1%±8.1%;P=0.001).The area under the curve of whole-body uptake for detecting IPVD was significantly higher than that of brain uptake (0.75 vs 0.54;P=0.025).The optimal cut-off values of brain uptake and whole-body uptake for detecting IPVD were 5.7%and 42.5%,respectively,based on Youden’s index.The sensitivity,specificity,and accuracy of brain uptake> 5.7%and whole-body uptake> 42.5%for detecting IPVD were23%,89%,and 59%and 100%,52%,and 74%,respectively.CONCLUSION Whole-body uptake is superior to brain uptake for diagnosing HPS.

^(99m)Tc标记的前列腺特异性膜抗原抑制剂HYNIC-P137的制备与临床转化

为开发低膀胱滞留的前列腺癌SPECT显像剂,在68 Ga-P137结构的基础上制备了^(99m)Tc-P137,对其进行临床前评估和初步的临床转化研究。通过固相合成方法制备标记前体HYNIC-P137,用EDDA作为共配体对前体进行^(99m)Tc标记,并对产物^(99m)Tc-P137进行质控。考察^(99m)Tc-P137的脂水分配系数和体外稳定性,考察其在PSMA阳性细胞和阴性细胞上的摄取和抑制。进行正常昆明小鼠的生物分布和荷瘤鼠的SPECT/CT显像,最后进行临床转化研究。结果表明,前体HYNIC-P137的固相合成方便易得,标记产物^(99m)Tc-P137的放化纯度接近100%,体外稳定性好,亲水性较强。正常昆明小鼠生物分布显示,该探针血液清除较快,主要通过肾脏代谢。荷瘤鼠的小动物SPECT/CT显示,^(99m)Tc-P137主要在PSMA阳性肿瘤和肾脏区域浓集,且均可被明显抑制,显示出高度的体内特异性。临床转化显示,^(99m)Tc-P137在膀胱蓄积较低,肝内放射性较高,对前列腺癌原位灶和淋巴结转移均具有良好的检出性能。研究表明,^(99m)Tc-P137有望成为高亲和性、低膀胱滞留的新型三七素类SPECT前列腺癌显像探针。

Quantitative Analysis of the Tomographic Technetium-99m MIBI (^(99m)Tc-MIBI) Myocardial Bullseye Display: Application to Diagnosis of Coronary Artery Disease

In this study, the 99mTc-MIBI myocardial bullseye display of 31 healthy persons and 34 patients with myocardial ischemia and 17 patients with myocardial infarction were analyzed quantitatively, and compared with the results of myocardial tomography analysis and qualitative bullseye analysis. The sensitivities of the three methods were 88.2%, 91.2 % and 94.1 % respectively (P>0.05),and the specificities were 93. 5%, 83, 9% and 83. 9% respectively (P<0.05).On the other hand, the quantitative analysis obviously outperformed the other two methods in the detection of ischemic segments of myocardium near infarction zone (P<0. 01). The quantitative analysis of 99mTc-MIBI myocardial bullseye (quantitative bullseye) was an objective, specific and sensitive method for diagnosis of coronary artery disease.

锝[^(99m)Tc]亚甲基二膦酸盐注射液中放化纯度薄层色谱分析方法的建立

为了建立一种测量锝[^(99m)Tc]亚甲基二膦酸盐注射液中放化纯度的可靠方法,本研究对分析方法的固定相和展开剂等条件进行研究,并按照《中国药典》等相关规定对分析方法进行方法学验证。结果表明,固定相为聚酰胺-6薄层板、展开剂为V(1 mol/L醋酸钠溶液):V(0.1 mol/L盐酸溶液)=1∶1混合溶液的单体系薄层色谱法,改善了锝[^(99m)Tc]亚甲基二膦酸盐注射液中放射性主峰的拖尾情况,且放射性主峰与高锝[^(99m)Tc]酸盐、胶体锝[^(99m)Tc]等潜在杂质的分离度>1.0,具有较好的专属性。经验证,建立的薄层色谱法在2.7×10^(-2)~42.4μCi放射性活度范围内线性关系良好,相关系数r为0.997,耐用性和中间精密度良好;与国内外药典收录的分析方法进行比对实验,放化纯度测试结果相对误差均<2.0%。本研究建立的单体系薄层色谱法适用于锝[^(99m)Tc]亚甲基二膦酸盐注射液放化纯度的测量。

一种新型含[^(99m)TcN]^(2+)核脑显像剂的初步研究

采用了SnCl2 ·2H2 O为还原剂 ,丁二酰二酰肼 (SDH)为N3- 离子提供体 ,在室温下制备[99mTcN]2 +中间体 ,然后与三水·N 环丁基 二硫代氨基甲酸钠 (CBDTC)发生配体交换反应得到放射化学纯度大于 90 %的99mTcN CBDTC配合物 .该配合物在室温下放置 6h内稳定 ,脂水分配系数结果表明该配合物是一脂溶性较好的物质 .小鼠体内生物分布表明99mTcN CBDTC在脑中有较好的摄取和滞留 ,脑的质量摄取率am ,br在注射后 5 ,30 ,6 0min时分别达到 3.6 1,3.15 ,2 .6 2 %·g- 1,脑与血的质量摄取率am ,br与am ,bl的比分别为 1.0 0 ,1.4 4,1.30 ,有望发展成为一类新型脑灌注显像剂 .

^(99m)TcN(NOET)_2的标记、生物分布及与^(99m)Tc-NOET的对比研究

采用三（间－磺基苯基）膦（TPPS）作还原剂制备而得99mTcN（NOET）2（NOET：N－乙氧基，N－乙基氨荒酸钠），经TLC检测标记物的放化纳大于90％．将99mTcN（NOET）2进行了大鼠体内生物分布测试，结果表明99mTcN（NOET）2心肌摄取快而且摄取率高，5min心肌摄取量XID（即每克组织中含量占总注射量的百分比）为5．22％g-1，心肌滞留时间长，60min为3．09％g-1，有望进一步进行临床研究，同时采用甲脒亚磺酸（FSA）作还原剂对NOET进行了99mTc直接标记，大鼠生物分布结果表明99mTc－NOET主要在肝内浓集，而心肌摄取很少，这也充分表明，放射性药物分于中［99mTcN］2＋核结构的变化引起生物分布性质的明显改变．

一种新型脑灌注显像剂^(99m)TcN-CPDTC的制备及生物分布

The complex 99m TcN CPDTC(CPDTC: N cyclopropyl dithiocarbamate trihydrate) is synthesized through ligand exchange reaction. The two step procedure involves the initial reaction of 99m TcO - 4 with succinic dihydrazide(SDH) as a donor of nitrido ligand(N 3- ) in the presence of stannous chloride dihydrate as reducing agent and propylenediamine tetraacetic acid(PDTA) as complex agent, followed by the addition of sodium N cyclopropyl dithiocarbamate trihydrate. The radiochemical purity(RCP) of the product is over 90% as measured by thin layer chromatography(TLC). It is stable over 6 h at room temperature. Its partition coefficient indicates it is a good lipophilic complex. The biodistribution results in mice indicate that 99m TcN CPDTC is significantly retained into the brain. The brain uptake(%, ID/g) is 4.64, 3 54 and 2.59 and the brain/blood ratio is 1.08, 1.27 and 1.28 at 5, 30 and 60 min post injection respectively. These results suggest potential usefulness of the complex as a brain perfusion imaging agent.

制备脂质体包裹的^(99m)锝标记c-myc mRNA反义寡聚核苷酸的研究

探讨脂质体包裹的 99m-锝标记 c- myc m RNA反义寡聚核苷酸的制备方法 ,为反义显像和反义治疗的实验研究奠定基础。合成 15 bp的反义寡聚核苷酸 (DNA)和双功能螯合剂 -联肼尼克酰胺衍生物 ,DNA与双功能螯合剂偶联后 ,用 99m锝标记 ,然后用 C1 8Sep- Pak反相柱进行纯化 ,根据纯化结果 ,绘制淋洗曲线 ,计算标记率。再用阳离子脂质体对纯化产物进行包裹 ,获得脂质体包裹的 99m锝 - DNA。用纸层析测定脂质体包裹的 99m锝 - DNA的放射性化学纯度及与水、血清孵育后的稳定性。结果 ,不同放射性活度的 99m Tc O4 - 标记时的标记率为 :14 80 MBq时为 6 3.37%± 3.5 1% ,74 0 MBq时为 6 2 .5 2 %± 3.6 9% ,5 92 MBq时为 5 9.82 %± 5 .12 % ,经 χ2检验无显著性差异。脂质体包裹 99m Tc- DNA的放射化学纯度 =96 .4 7%± 3.0 1% ,与水、血清孵育后脱落的 99m Tc极少 ,可见 99m Tc- DNA的稳定性极好。由此可见 ,以脂质体作载体 ,联肼尼克酰胺衍生物作为双功能螯合剂 ,可制备脂质体包裹的

^(99m)Tc-DTPA肾动态显像对IVP不显影患肾功能的评价

目的:探讨放射性核素^(99m)Tc-DTPA肾动态显像对静脉肾盂造影(IVP)不显影患肾功能评价的临床意义。方法:受检者共64例,临床诊断共66只患肾。^(99m)Tc-DTPA静脉注射后SPECT肾动态显像,获取血流灌注和功能显像图像并测定分肾GFR值。结果:IVP不显影的患肾^(99m)Tc-DTPA动态显像结果表现为0级2例,GFR均值为53.7ml/min;I级3例,GFR均值为35.8ml/min;II级7例,GFR均值为21.1ml/min;III级36例,GFR均值12.8ml/min;IV级18例,GFR均值为7.8ml/min。对^(99m)Tc-DTPA动态显像提示另一肾脏功能正常或轻度受损的患者手术切除患肾20例,其余行保留肾脏治疗手段,大部分功能恢复良好。结论:^(99m)Tc-DTPA肾动态显像对评价肾功能,特别是对IVP不显影的单肾功能判定有重要的临床价值,此法具有简便、无创伤、灵敏度高及可重复性的特点。

^(99m)Tc-HL91肿瘤阳性显像的初步临床评价

目的:研究乏氧显像剂99mTc-HL91作为肿瘤阳性显像剂的价值及最佳显像条件。方法:对25例临床确诊的恶性肿瘤患者进行99mTc-HL91平面及断层显像,通过划感兴趣区技术计算肿瘤与正常组织的放射性比值。结果:平面显像显示肿瘤的效果较差,而断层显像及延迟显像效果较好。以TNT值为1.5为标准,99mTc-HL91显像检测病灶的灵敏度为90.6%。结论:99mTc-HL91乏氧显像是一种较灵敏和特异的肿瘤阳性显像检测方法。

^(99m)Tc-MIBI与^(99m)Tc-PPM肺肿瘤阳性显像的对比研究

目的：对比分析99mTc-甲氧基异丁基异睛（MIBI）与99mTc-培普利欧霉素（PPM）肺肿瘤显像的特点与诊断效能。方法：对48例使用99mTc－MIBI与39例使用99Tc－PPM肿瘤阳性显像的结果通过目测观察，T／N（肿瘤与非肿瘤）比值测定，储存指数RI测定，延迟显像摄取指数DUI测定并对其结果进行对比。结果：目测观察，99mTc－MIBI显像对恶性肿瘤诊断的灵敏度为94．12％（32／34），特异性为85．71％（12／14），99mTc－PPM显像对恶性肿瘤诊断的灵敏度为90.91％（30／33），特异性为83．33％（5／6），两者之间无显著性差异（P＞0．05）；99mTc－MIBI在恶性肿瘤组早期T／N为1．36,晚期T／N为1．37，RI值为0．74DUI值为1．38，而99mTc-PPM在恶性肿瘤组分别为1．13，1．3611．77及1．64，其中两组早期T／N之间，晚期T／N之间均无显著性差异（P＞0．05），两组RI值之间有非常显著性差异（P＜0．01），两组DUI之间有显著性差异（P＜0．05）；两种显像剂在良性病变组各参数之间的差异均无显著性（P＞0.05）。结论：99mTc-L－MIBI及99mTc－PPM肺肿瘤阳性显像对肺肿瘤的诊断及鉴别其良恶性有一定价值；恶性肿瘤对两种显像剂的外排存在差异。

^(99m)TcN-GLA的制备及其生物分布研究

将99mTcO- 4与浓HCl和NaN3在沸水浴的条件下制备99mTcNCl- 4中间体 ,然后与配体葡萄糖二酸 (GLA)发生交换反应得到放化纯度大于 90 %的99mTcN GLA配合物 .小鼠体内生物分布结果显示 :99mTcN GLA与99mTc GLA有明显不同的生物分布 ,特别是99mTcN GLA的肺摄取及滞留均较好 ,有望成为一种新型的肺显像剂 .

^(99m)Tc标记环己二酮二肟及其甲基硼酸加成物和初步动物实验

实验结果表明,^(99m)Tc-CDO的标记率受体系的pH值影响较小,而^(99m)Tc-CDO-MeB只有在pH=3.5—4.0时标记率才能大于90％。小鼠体内分布实验表明,^(99m)Tc-CDO-MeB在动物心肌中有较高的吸收,但随时间延长而迅速清除。心/肝比值在给药后1、5和10min时分别为3、1.5和0.8。^(99m)Tc-CDO在心、脑中的浓聚明显低于^(99m)Tc-CDO-MeB。

^(99m)TcN核标记的新型心肌灌注显像剂的研究

通过配体交换反应制备了[99mTcN(PNP5)(DEDC)]+和[99mTcN(PNP5)(DPODC)]+两种新配合物,其放化纯度均大于90%.生物性能研究结果表明:两种配合物在小鼠心肌中的初始摄取高,肝、肺等非靶组织清除快,靶/非靶比高,有利于早期心肌显像.其中,[99mTcN(PNP5)(DEDC)]+在小鼠中的性质较优,且其在狗体内的性质接近99mTc-tetrofosm in,有望成为一种新型心肌灌注显像剂.

^(99m)Tc-MIBI核素显像与CT在原发性甲状旁腺功能亢进症中的诊断价值

目的:通过对术前^(99m)Tc-甲氧异腈(MIBI)核素显像与CT图像分析,探讨分析两者在原发性甲状旁腺功能亢进症中的临床诊断价值。方法:回顾分析经病理证实的38例原发性甲状旁腺功能亢进症患者术前^(99m)Tc-MIBI核素显像和CT影像资料,比较^(99m)Tc-MIBI核素显像、CT、^(99m)Tc-MIBI核素显像与CT联合3种影像学方法对原发性甲状旁腺功能亢进症的诊断灵敏度差异。结果:^(99m)Tc-MIBI核素显像、CT、^(99m)Tc-MIBI核素显像与CT联合3种影像学方法诊断原发性甲状旁腺功能亢进症的灵敏度分别为89.65%、64.00%、93.75%;统计分析显示^(99m)Tc-MIBI核素显像组与CT组、CT组与联合组之间差异有统计学意义,^(99m)Tc-MIBI核素显像与CT联合组灵敏度优于其它两种方法。结论:术前^(99m)Tc-MIBI核素显像与CT对原发性甲状旁腺功能亢进症的评估均是必要的,两者联合应用可提高原发性甲状旁腺功能亢进症的诊断价值。

^(99m)Tc-MIBI甲状腺显像半定量分析鉴别甲状腺结节的价值

目的 :评价99mTc MIBI甲状腺显像半定量分析法鉴别甲状腺结节的价值。材料和方法 :3 6例Na99mTcO4甲状腺显像为单发“冷结节”患者 ,行99mTc MIBI甲状腺双时相显像 ,分别计算 15和 12 0min甲状腺结节摄取比值 (ER、DR) ,以良性结节组的DR均值 +标准差 ( 0 .90 +0 .2 1)为诊断恶性病变的阈值。结果 :手术证实良性病变 2 2例 ,ER与DR值分别为0 .89± 0 .3 3、0 .90± 0 .2 1,恶性病变 14例 ,ER和DR值分别为 1.16± 0 .5 1、1.3 4± 0 .64 ,ER值两组间比较无差异 (p >0 .0 5 ) ,DR两组间比较有显著性差异 (p <0 .0 1)。99mTc MIBI甲状腺显像DR值诊断良恶性病变的灵敏度 85 .7% ,特异性 86.4% ,阳性预测值 80 .0 % ,阴性预测值 90 .5 %。结论 :99mTc MIBI甲状腺显像半定量分析能较好的鉴别甲状腺结节的性质 ,DR比ED更有价值。