First experience in healthy volunteers with technetium-99m l,l-ethylenedicysteine,a new renal imaging agent

Animal studies have indicated that technetium-99m l,l-ethylenedicysteine (^99mTc-l,l-EC) may be a promising tracer agent for renal function studies. We have performed a paired study with ^99mTc-mercaptoacetyltriglycine (^99mTc-MAG₃) and ^99mTc-l,l-EC in six male volunteers. In both cases, iodine-131-labelled o-iodohippurate was co-injected as an internal biological standard. The analog images between 0 and 30 min p.i. were of identical diagnostic value for both tracer agents. The two renograms were similar in all volunteers. The mean 1-h plasma clearance for ^99mTc-MAG₃ and 99 mTc-l,l-EC was significantly different, respectively 382.9 ± 17.1 ml/min per 1.73 m² versus 460.2 ± 47.7 ml/min per 1.73 m² (P<0.003). The urinary excretion after 30 min p.i. was 69.4% ± 5.6% of the injected dose for ^99mTc-MAG₃ versus 66.5% ± 2.5% for ^99mTc-l,l-EC (P>0.05) and after 60 min p.i. respectively 83.1% ± 3.9% versus 79.8 % ± 4.3 % (P > 0.05). ^99mTc-l,l-EC has a very low plasma protein binding (31% ± 6.8%) as compared to ^99mTc-MAG₃ (88% ± 5.2%) and a larger volume of distribution. Although the exact mechanism responsible for the high plasma clearance of ^99mTc-l,l-EC is not yet fully known, we conclude that this new agent merits further clinical evaluation in patients to establish its value as a renal radiopharmaceutical. Correspondence to: A. Verbruggen     

Reproducibility of quantitative hexakis-2-methoxyisobutylisonitrile single photon emission tomography in stable coronary artery disease

The quantification of myocardial perfusion abnormalities is necessary to allow comparison of repeated studies, especially in the evaluation of the success of medical, interventional or combined treatment in stable coronary artery disease or in evolving myocardial infarction. The purpose of this study was to assess inter-observer reproducibility of tomographic study processing using a semi-automatic quantitative programme. Technetium 99m hexakis-2-methoxyisobutylisonitrile (^99mTc-Sestamibi) was chosen for tomographic imaging of repeated rest-stress studies in patients with stable coronary artery disease. The quantification was performed using a modification of the Cedars polar coding and comparison with the normal data base. The perfusion defects were quantified separately for each standard perfusion area [left anterior descending (LAD), right coronary (RCA) and left circumflex (LCX) arteries] and total area of hypoperfused myocardium. The inter-observer variability for 40 tomographic studies was accomplished. The defects were the largest in the LAD perfusion area (average 19.7% of the normalized LAD supply area) with an inter-observer correlation of 0.84 for this region. The greatest variability was found for the LCX region (r=0.55) and is attributed to a small average perfusion defect (7.1%), only 18 studies having abnormal perfusion in this area. In total, an average 14.3% of the left ventricular myocardium was significantly hypoperfused, and the inter-observer correlation was 0.87. These results show good inter-observer reproducibility using semi-automatic quantitation of perfusion defects. Careful interpretation of smaller defects in the evaluation of treatment results is advised when repeated ^99mTc-Sestamibi single photon emission tomography studies are processed by more than one observer.The work was performed at Nuclear Medicine Department in Ulm. Offprint requests to: M. Milinski     

Iodine-125 labeled phenylphosphonic acid: A new radiopharmaceutical for long-term investigations of the skeleton

A skeletal seeking radiopharmaceutical labeled with a long-lived radionuclide was developed to evaluate regional bone formation and its subsequent resorption. The agent is [phosphonate (phenylmethylene hydroxy) bis]-I-125 or I-125 PA. Tissue distribution studies in mice (N=16) showed approximately 40% of the administered dose to be retained by the skeleton up to 336 hours post IV injection. The percentage of the dose accumulated by the thyroid gland remained at less than 0.5%, indicating minimal deiodination of the I-125 PA. Whole body retention studies in the same species revealed a triexponential release pattern with the longest component comprising 33% of the dose with a biologic half-life of 962 days. A fractured rat tibia model was studied with I-125 PA and Tc-99^m MDP. Chronic loss of the I-125 PA relative to normal tibia was quantitated: five days (62.8%); 30 days (47.4%). Concomitant increased uptake of the Tc-99^m MDP was observed at the fracture site relative to normal: five days (186%); 30 days (1,041%). The above data suggest that I-125 PA can be utilized to measure acute bone formation and chronic resorption.     

探讨肝胆高放射性对心肌下壁显像的影响

目的 探讨用^99mTc-Sestamibi(^99mTc-MIBI）作心肌显像时减少肝胆放射性对心肌下壁影响的方法。方法 研究12例1h显像出现肝胆放射性高的患者其3h延迟显像，比较其心/肝计数比值及下壁/前壁计数比值，并进行t检验。结果 本研究观察12例肝胆放射性高的患者，其1h心肌显像下壁放射性稀疏缺损，心/肝比值低；而3h延迟显像时，心/肝比值显著增高，且下壁的放射性稀疏则明显减轻或消失。对照组1和3h显像的心/肝比值也有明显增高。但其1h心肌血流灌注断层显像发现下壁放射性减低时，应观察原始图象的肝胆放射性，必要时加做3h延迟显像，排除伪影干扰。     

Synthesis of a technetium‐99m labelled L‐tyrosine derivative with the fac‐99mTc(I)(CO)3‐core using a simple kit‐procedure

The synthesis of a novel technetium‐99m labelled derivative of L ‐tyrosine as a potential tumour imaging agent for nuclear medicine diagnosis is reported. The synthesis involved the labelling precursor fac‐[^99mTc(OH₂)(CO)₃]⁺ which was synthesized using the commercially available Isolink^®‐labelling kit and the tyrosine derivative O‐(N,N‐bis(carboxymethyl)aminoethyl)‐L ‐tyrosine trifluoroacetate. The labelled compound O‐(^99mTc(I)‐tricarbonyl‐N,N‐bis(carboxymethyl)aminoethyl)‐L ‐tyrosine was obtained in a radiochemical yield of 70–80% within 60 min with a radiochemical purity greater than 98% without any HPLC purification step. Purification was achieved merely by solid phase extraction. Chemical as well as chiral purity was determined using gradient‐ and chiral HPLC. Copyright © 2004 John Wiley & Sons, Ltd.     

鼻咽癌面颈联合野放疗对唾液腺功能影响的临床分析

目的 :利用放射性核素99mTcO4-动态显像唾液腺定量测定鼻咽癌面颈联合野放疗前、中、后唾液腺功能的变化并探讨与放疗剂量之间的关系。方法 :2 0 0 3年 2月 1日～ 2 0 0 3年 10月 3 1日 ,分别对 2 0例鼻咽癌面颈联合野放疗患者于放疗前、放疗至 10、3 6～ 40、70Gy时进行99mTcO4-动态显像定量测定其唾液腺(腮腺、颌下腺 )摄锝率 (UR)、泌锝率 (ER)变化 ,同时观察其口干程度进行临床分级。结果 :2 0例鼻咽癌面颈联合野放疗剂量为 10和3 6～ 40Gy时 ,其泌锝率明显低于放疗前 ,P <0 0 5 ,在放疗 70Gy时降到最低 ,P <0 0 1。与临床观察到的口干严重程度一致 ,而其摄锝率在 3 6～ 40Gy照射以前变化不明显 ,无统计学意义。结论 :鼻咽癌面颈联合野照射患者放疗前无明显唾液腺功能障碍 ,随着放疗剂量的增加 ,唾液腺功能明显下降 ,其ER较UR下降明显 ,在确保患者放疗疗效的同时 ,应尽可能提高放疗技术 ,减少唾液腺照射剂量和放疗体积 ,保护唾液腺功能 ,以提高患者的生活质量。     

提高乳腺癌早期诊断水平的研究

目的：评价育龄妇女乳腺疾病普查、乳腺钼靶摄片及^99mTc-MIBI核素显像在乳腺癌早期诊断中的价值，探索提高乳腺癌早期诊断的方法。方法：对徐州地区10万例育龄妇女进行乳腺疾病的普查，筛选出的乳腺癌高危人群及门诊就诊的乳腺疾{戎患者行乳腺钼靶摄片及^99mTc-MIB核素显像检查。结果：普查乳腺癌检出率为28．9／10万。乳腺钼靶摄片诊断乳腺癌的灵敏度为90．2％、特异性为31.4％。^99mTc-MIBI核素显像灵敏度为82．5％，特异性为90．2％。联合应用乳腺钼靶摄片与^99mTc-MIBI核素显像，对乳腺癌诊断的灵敏性为100％，特异性为99．3％。结论：育龄妇女乳腺疾病普查，结合乳腺钼靶摄片及^99mTc-MIBI核素显像可以明显提高乳腺癌的诊断率。     

99m Tc-HL91 "hot spot" imaging of mice bearing human carcinoma by gamma camera and the effects of tumor necrosis on imaging

Objective To evaluate the hypoxia-avid agent ^99m Tc-HL91 (^99m Tc labeled 4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime) as the tracer of tumor "hot spot" imaging and the influence of tumor necrosis on the image.
Methods After injection of ^99m Tc-HL91, 6 nude mice bearing human breast cancer MCF-7 and 18 nude mice bearing human pancreatic adenocarcinoma were subjected to gamma camera imaging, postmortem analysis, and autoradiography and imaging of tumor sections.
Results The image of tumor was identified 1 hour after injection of ^99m Tc-HL91.Images demonstrated gradually increased ^99m Tc-HL91 uptake in the tumor 1-12 hours after injection (P<0.05-0.001).Six hours after injection, the radioactivity ratios of tumor to thorax and tumor to head were higher than 2.1.Six hours after injection, the radioactivity ratios of tumor to brain, muscle, blood, heart, lung and kidney in pancreatic adenocarcinoma bearing nude mice were 101.0±114.7, 30.0±30.3, 19.9±21.9, 14.4±15.1, 3.71±2.41 and 0.46±0.26, respectively, and the radioactivity ratios in breast cancer MCF-7 bearing nude mice were close to these figures.The radioactivity of non-necrotic tumor was 3.77 times that of necrotic tumor.However, the radioactivity ratios of tumor to liver, intestine and stomach were lower than 1.3. Autoradiographs and images of tumor sections showed that the radioactivity was higher in the region of solid tumor than in the necrotic region.
Conclusion ^99m Tc-HL91 via gamma camera positively identifies regional tumor in nude mice bearing human cancer.^99m Tc-HL91 retention is lower in necrotic tumor than in non-necrotic tumor.The low radioactivity ratio of tumor to abdominal organs limits the application of ^99m Tc-HL 91 in detecting abdominal tumors.      

The comparison of dual phase Tc-99m MIBI and Tc-99m MDP scintimammography in the evaluation of breast masses: Preliminary report

The aim of this prospective study was to determine the diagnostic value of Tc-99m MDP scintimammography (SMG) for the detection of breast cancer in patients with breast masses and to compare the results with Tc-99m MIBI scintimammography. Twenty patients, categorized as suspicious, positive or benign for breast cancer according to the mammographic findings were included in the study. Dual phase Tc-99m MIBI and Tc-99m MDP SMG were performed in the prone lateral position within 5 days of each other. Although early and late Tc-99m MIBI SMG showed equal (90.4%) sensitivity, the specificity of late Tc-99m MIBI (87.5%) was found superior to early (62.5%) imaging. The overall sensitivity and specificity of early Tc-99m MDP SMG were 71.4% and 62.5%, respectively. Although late Tc-99m MDP imaging showed 100% specificity, its sensitivity was only 23.8%. In the patients with palpable masses, both early Tc-99m MDP and Tc-99m MIBI showed equal sensitivity (100%), but the sensitivity of early Tc-99m MIBI (37.5%) was found slightly higher than Tc-99m MDP (25.0%) for nonpalpable breast lesions. The sensitivity of Tc-99m MIBI and Tc-99m MDP SMG in detecting metastatic axillary involvement was 66.6% and 50%, respectively. High sensitivity and specificity together with its low cost, easy availability and the possibility of detecting bone metastases seems to make Tc-99m MDP a contributive agent in the evaluation of breast lesions as an alternative to Tc-99m MIBI.     

Technetium-99m labeling of a molecule bearing easily reducible groups

Chemical stability of the naphthol-azo dye Evans Blue (EB) was examined in the presence of acidic stannous chloride (SnCl₂), with a view to preparing an instant cold kit. EB was found to be reactive toward this reducing agent, yielding the metal-chelating molecule 1,7-diamino-8-naphthol-2,4-disulfonic acid at high acidity and high stannous concentrations. This reduction reaction was undesirable in the cold kit preparation. The conditions were determined where reduction was inhibited, at pH = 5.0 and with a mole ratio of EB to SnCl₂ = [10:1], effecting the facile preparation of stable cold kits. Successful ^99mTc-labeling of an EB cold kit using these conditions resulted in the desired product with 98% radiochemical purity. Based on the radiolabeling efficiencies of chosen model compounds, it was rationalized that ^99mTc metal predominantly coordinated with the 1-amino-8-hydroxy groups in the EB molecule to form ^99mTc-EB.