99Tcm-替曲膦与99Tcm-MIBI心肌灌注显像诊断无症状心肌缺血的比较研究

目的 比较99Tcm-替曲膦(TF)与99Tcm-MIBI腺苷负荷-静息MPI在无症状心肌缺血(SMI)患者中的应用价值.方法 选择符合WHO冠心病诊断标准的Ⅰ、Ⅱ、Ⅲ型SMI患者,分别为122、112和72例,各型SMI均按完全随机法分为2组,分别行99Tcm-MIBI及99Tcm-TF腺苷负荷-静息MPI.306例患者的冠心病经心电图(46例)、动态心电图(219例)和CAG(41例)证实.比较2种显像方法的心肌缺血诊断灵敏度及原始图像质量.数据比较采用x2检验及方差分析.结果 按照心肌缺血诊断标准(负荷显像节段性放射性稀疏或缺损处静息显像时明显填充),99Tcm-MIBI和99Tcm-TF心肌显像诊断心肌缺血的灵敏度分别为:Ⅰ型:57.38％(35/61)和60.66％(37/61),x2=0.136,P＞0.05;Ⅱ型:69.64％(39/56)和64.29％(36/56),x2=0.363,P＞0.05;Ⅲ型:83.33％(30/36)和88.89％(32/36),x2=0.465,P＞0.05,3型SMI患者各2组间诊断心肌缺血的灵敏度差异均无统计学意义.原始图像质量方面,99Tcm-MIBI及99Tcm-TF显像图优(心肌影像清晰,无肝、肺、血本底干扰)者百分比分别为41.18％(63/153)和48.37％(74/153),x2=1.599,P=0.206;良(心肌影像尚清晰,但肝可见放射性,无明显血液本底)者百分比分别为45.10％(69/153)和34.64％(53/153),x2=3.489,p=0.062;中(心肌显影,肝放射性高,血液本底低)者百分比分别为13.72％(21/153)和16.99％(26/153),x2=0.628,P=0.428,差异均无统计学意义.图像总体质量良好,无不合格图像.注射99Tcm-TF者较注射99Tcm-MIBI者肝、肺放射性清除快,与心肌放射性摄取差异较大,对心脏下壁及心尖部显示影响较小,且至少缩短1h待检时间.结论 99Tcm-TF可获得与99Tcm-MIBI同等的心肌缺血诊断显像效果,且肝、肺清除快,图像质量较好,可有效缩短患者待检时问,有很好的应用前景.     

99mTc-MIBI检测肺癌耐药性的作用研究

目的拟探讨99mTc-MIBI能否检测肺腺癌A549DDP细胞的耐药性及人参单体Rh2作用后A549DDP细胞对顺铂耐药性的变化.方法用MTT法检测顺铂对敏感A549细胞和耐药A549DDP细胞的IC50、对A549DDP细胞的低效浓度(≤IC20),Rh2对A549DDP细胞的无毒浓度(≤IC5).以无毒浓度Rh2和低效浓度的顺铂联合作用于A549DDP细胞,检测Rh2对顺铂抑制A549DDP细胞的影响.以无毒浓度的Rh2单独作用于A549DDP细胞作为Rh2组,以低效浓度的顺铂单独作用于A549DDP细胞作为DDP组,以无毒浓度的Rh2和低效浓度的顺铂联合作用于A549DDP细胞作为Rh2+DDP组,以不加药物干预作为对照组,Hoechst33258染色荧光显微镜下观察细胞形态的变化,流式细胞仪检测细胞凋亡峰.γ计数器检测以上4组细胞及A549细胞的放射性活性.将以上细胞注入裸鼠皮下建模后,用99mTc-MIBI进行SPECT显像.结果順铂对A549细胞、A549DDP细胞的IC50分别为24、325 μmol/L,耐药指数为13.54.Rh2≤10 μmol/L时,对A549DDP细胞无明显毒性作用;100 μmol/L顺铂对A549DDP细胞的抑制率为12%.10 μmol/L Rh2与100 μmol/L顺铂联合作用,顺铂对A549DDP细胞的IC50降为94 μmol/L,与100 μmol/L顺铂单独作用于A549DDP细胞的IC50比,逆转3.5倍.荧光显微镜下,Rh2组和DDP组的大部分细胞核和对照组的一样,荧光分布均匀;Rh2+DDP组的荧光成团块分布,有凋亡小体形成.对照组、Rh2组和DDP组的细胞无明显凋亡峰,而Rh2+DDP组则出现了显著的凋亡峰.各组A549DDP细胞和A549细胞均能摄取99mTc-MIBI,Rh2组和DDP组与对照组之间细胞的放射性活性差异无统计学意义,而Rh2+DDP组则较对照组细胞的放射性活性显著性降低,P<0.05.A549细胞的放射性活性显著性高于A549DDP细胞的对照组,P<0.01.99mTc-MIBI 显像,A549组裸鼠可见瘤块的放射性浓聚影.A549DDP对照组和DDP组裸鼠亦可见瘤块的放射性浓聚影,其放射性浓度较A549组淡,这两组间的R或R′差异无统计学意义,但与A549组比较,P<0.05.DDP+Rh2组裸鼠无肿瘤生长,局部未见明显放射性浓聚影.结论 99mTc-MIBI能检测肺腺癌耐药的A549DDP细胞的耐药性;无毒浓度的Rh2能有效逆转A549DDP细胞对顺铂的耐药性,这种耐药性的变化亦能被99mTc-MIBI有效检测.     

Lung scan abnormalities in asthma and their correlation with lung function

We have used asthma as a model of airways disease to test how well an automated, quantitative method of analysis of lung scans correlates with physiological measurements of disturbed lung function and gas exchange. We studies 25 asthmatics (age 16–73) of widely differing severity (forced expiratory volume in 1-s (FEV₁) 22% 123% of predicted value), who had airways tests, arterial blood gas analysis, and krypton-technetium lung scans within a short time of each other. In all patients with airways obstruction and in some with normal function during remission, scans showed the typical appearances of multiple defects of ventilation and perfusion. The severity of ventilation defects was computed from the posterior view of the krypton scan compared to an age- and sex-matched normal range to yield an underventilation score. This correlated closely with the severity of airways obstruction as measured by forced expiratory manouevres. Ventilation and perfusion defects were usually imperfectly matched; the severity of this was computed using a subtraction method applied to the counts on the posterior krypton and technetium scans. The degree of mismatch was inversely related to the arterial partial pressure of oxygen (r=-0.86). The results suggest that computer scan analysis can provide useful functional information about the lung in airways disease.     

Technetium,the missing element

The history of the discovery of technetium is reviewed within the framework of the discovery and production of artificial radioactivity in the twentieth century. Important elements of this history are the accidental production of this element in a cyclotron in Berkeley, California, USA, a machine devised by Ernest Orlando Lawrence, and its subsequent discovery in 1937 by Carlo Perrier and Emilio Segrè in scrap metal parts sent by Lawrence to Palermo, Italy by mail. A detailed account is given of the steps taken; the history of the later discovery of the technetium-99m isotope in 1938 is likewise examined. Sources of natural and artificial technetium are briefly discussed.This paper is dedicated to Carlo Perrier (1886–1948) and Emilio Segrè (1905–1989)     

Urinary bladder blood flow

Summary The blood flow of the dog urinary bladder measured by radioactive microsphere technique was compared to the clearance of locally injected ^99mTechnetium pertechnate (^99mTc) in the bladder wall. In semilogarithmic plots the ^99mTc washout curves showed a multiexponential course. From the initial slopes (median 5.7 min) the bladder blood flow was calculated to be only 30–62% of the results obtained from the radioactive microsphere technique (blood flow in the muscular layer 21.7–44.8 ml/ 100 g/min). These lower values imply that the rate of removal of the hydrophilic tracer ^99mTc at these flow rates is limited by the capillary diffusion capacity. The multiexponential curves reflect recirculation and excretion of ^99mTc by the kidneys with accumulation of ^99mTc in the bladder. It is concluded, that clearance studies of locally injected ^99mTc in the bladder wall are unable to evaluate bladder blood flow.     

Measurement of synovial inflammation in rheumatoid arthritis with technetium 99m labelled human polyclonal immunoglobulin G

The ability of technetium 99m labelled nonspecific, polyclonal human immunoglobulin G (^99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in patients with rheumatoid arthritis (RA). Eight patients with clinically active synovitis were injected with 350 MBq ^99mTc-IgG, and imaging took place 4 h later. This resulted in excellent images of inflamed synovium. Significant correlations were observed between individual joint uptake on the scan and scores for joint pain (n=316, p<0.001), joint swelling (n = 300, p < 0.001) or the average of pain and swelling (n = 300, p < 0.001). These results suggest that ^99mTc-IgG scintigraphy may provide an objective, non-invasive test to detect and measure synovitis. Offprint requests to: P.A.H.M. van der Lubbe     

99Tcm-DTPA-环九肽用于前列腺癌骨转移白细胞介素11受体显像的实验研究

目的 建立99Tcm标记白细胞介素11（IL11）类似物环九肽,即环状肽半胱氨酰-甘氨酰-精氨酰-精氨酰-丙氨酰-甘氨酰-甘氨酰-丝氨酰-半胱氨酸[c（CGRRAGGSC）]的方法,探讨标记物用于前列腺癌骨转移IL11受体（IL11R）显像的可行性.方法 采用间接法,用99Tcm标记c（CGRRAGGSC）制备99Tcm-DTPA-环九肽[99Tcm-DTPA-Bz-NH-SA-c（CGRRAGGSC）,简称99Tcm-DTPA-IL11RR].利用纸层析法及高效液相色谱（HPLC）测定标记率和稳定性.将99Tcm-DTPA-IL11RR（0.74 MBq/只）经正常ICR小鼠尾静脉注射后,观察其在小鼠体内生物学分布,计算血、脑、心、肝、脾、肺、肾、胃、小肠、肌肉、甲状腺、骨骼、胰腺每克组织百分注射剂量率（%ID/g）.γ显像动态（5只小鼠）观察99Tcm-DTPA-IL11RR在荷人PC-3前列腺癌骨转移瘤BALB/c裸鼠模型体内0.5,1,2,4,6,8和24 h表现,与99Tcm-亚甲基二膦酸盐（MDP）骨显像比较,采用感兴趣区（ROI）法计算99Tcm-DTPA-IL11RR显像肿瘤/对侧正常骨骼放射性（T/NT）比值,并用此2种显像剂进行裸鼠骨折模型显像比较.进行体内竞争抑制显像（3只荷瘤裸鼠）,观察标记物生物学活性.对计量资料数据行单因素方差分析.结果 99Tcm-DTPA-IL11RR标记率90.7%,HPLC即时测放化纯为（99.57±0.09）%,室温放置1,2,3,4,6,8和24 h,放化纯依序为（99.29±0.18）%,（98.95±0.78）%,（98.67±0.11）%,（96.53±0.91）%,（95.20±0.70）%,（88.38±0.22）%和（36.17±1.29）%.标记物经正常ICR小鼠尾静脉注射后主要经肾排泄,各时相重要组织脏器普遍摄取较低,肌肉和脑最低,4 h骨骼、肝摄取达峰值,分别为（1.910±0.109）和（0.366±0.030）%ID/g.注射后24 h体内放射性消失.模型鼠γ动态显像示脊柱骨髓、四肢关节髓腔轻度显影,体内放射性清除迅速;瘤灶放射性持续摄取,4 h最明显,延续至6～8 h;24 h全身影像极淡.以ROI法测量的模型鼠0.5,1,2,4,6,8和24 h T/NT比值分别为1.17±0.17,2.20±0.29,3.20±0.15,3.67±0.23,13.61±0.85,9.45±0.37和3.33±0.30（F=621.54,P＜0.05）.骨折模型99Tcm-MDP显像示骨折处放射性摄取,99Tcm-DTPA-IL11RR显像未见摄取.体内竞争抑制实验示环九肽对瘤体显像具有抑制作用.结论 99Tcm-DTPA-IL11RR标记率高,稳定性好,有望成为前列腺癌等富含IL11R的骨转移特异分子靶向显像剂.     

Synthesis,radiolabeling and in vitro and in vivo characterization of a technetium‐99m‐labeled alpha‐M2 peptide as a tumor imaging agent

Abstract: In an effort to develop a peptide‐based radiopharmaceutical for the detection of breast cancer, we have prepared an analog of αM2 peptide, modified to incorporate an N₃S chelate system. Mercaptoacetyltriglycine (MAG)₃‐derivatized αM2 peptide was prepared by solid‐phase synthesis and radiolabeled with ^99mTc by an exchange method. In vitro cell‐binding on human breast cancer cell lines, MDA‐MB‐231 and MCF‐7, indicated the affinity and specificity of ^99mTc‐MAG₃‐αM2 toward breast cancer cells. Additionally, the radiolabeled peptide showed rapid internalization into human breast cancer cells. In vivo biodistribution in mice showed that the radiolabeled peptide cleared rapidly from the blood and most non‐target tissues and was excreted significantly via the kidneys. Uptake of ^99mTc‐MAG₃‐αM2 in the tumor was moderate. The radiochemical and in vitro and in vivo characterization indicates that the radiolabeled peptide has certain favorable properties and it might be a useful radiopharmaceutical for the detection of breast cancer in vivo.     

Development of a novel 99mTc‐labeled small molecular antagonist for CXCR4 positive tumor imaging

The chemokine receptor 4 (CXCR4) has been an attractive molecular target for tumor imaging, because it is overexpressed in many tumor types and involved in tumor progression and metastasis. The purpose of this study is to examine the CXCR4 targeting properties of ^99mTc‐labeled AMD3465, a small molecule antagonist of CXCR4. ^99mTc‐AMD3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 hours. In vitro cell binding experiments were performed with Chinese hamster ovary (CHO), MCF‐7 (breast cancer), and CHO‐CXCR4 (CHO stably transfected to express CXCR4) cell lines. Small animal single photon emission computed tomography/computed tomography imaging studies in nude mice bearing MCF‐7 and CHO xenografts showed that the uptakes of the radiotracer in MCF‐7 tumors were significantly higher than those in the CXCR4‐negative CHO tumors (P < 0.05), and the MCF‐7 tumors uptake could be blocked with an excess of unlabeled AMD3465 (P < 0.05). These results suggested that ^99mTc‐AMD3465 could be a potential single photon emission computed tomography radiotracer for CXCR4 imaging.     

^18F—FDGPET显像与^99Tc^m-MDP全身骨显像诊断肿瘤骨转移价值的比较

目的评价^18F-脱氧葡萄糖（FDG）PET肿瘤显像与^99Tc^m-亚甲基二膦酸盐（MDP）全身骨显像诊断肿瘤骨转移价值。方法43例肿瘤患者,其中28例经其他检查或随访证实为骨转移,15例证实无骨转移。2周对患者内行^18F—FDGPET和^99Tc^m-MDP显像,比较分析两种显像结果。结果28例肿瘤骨转移患者中,^18F—FDG PET阳性26例,^99Tc^m-MDP阳性27例,灵敏度分别为92．9％（26／28）、96.4％（27／28）,差异无统计学意义（P〉0．05）。15例无骨转移患者中,PET阴性14例,MDP阴性8例,特异度分别为93．3％（14／15）、53．3％（8／15）,差异有统计学意义（P〈0．01）。两种方法检测骨转移的准确率分别为93．0％（40／43）、81．4％（35／43）,差异有统计学意义（P〈0．01）。结论^18F—FDGPET诊断肿瘤骨转移的灵敏度与^99Tc^m-MDP显像相近,但特异性和准确性均较高。对^99Tc^m-MDP骨显像阴性、单一病灶及可疑骨转移患者,进一步行^18F—FDG PET显像,可起到信息互补、明确诊断的作用。