直接还原法标记^99mTc与抗人膀胱癌单克隆抗体BDI—1

通过２ － 巯基乙醇直接还原法将抗人膀胱癌单克隆抗体 Ｂ Ｄ Ｉ－ １ 与核素９９ｍ Ｔｃ 进行标记, 制备９９ ｍ Ｔｃ － Ｂ Ｄ Ｉ－ １ ． 优化条件后进行标记并进行一系列检测． 结果： 标记率为７２ ％ , 经 Ｓｅｐｈａｄｅｘ 柱纯化后标记抗体的放化纯度高于９５ ％ ; 标记抗体的免疫活性分数为８７ ％ , 与 Ｅ－ Ｊ细胞的结合率为９０ ％ ; 无毒、无菌、无热原． 结果表明： ２ － 巯基乙醇直接还原法将抗人膀胱癌单克隆抗体 Ｂ Ｄ Ｉ－ １ 与核素９９ ｍ Ｔｃ 进行标记为进一步进行膀胱癌的放射免疫显像诊断奠定了基础．     

Clinical Validation of a New Immunoradiometric Assay for Intact Human Osteocalcin

The purpose of this study was to estimate clinical validity of a new available immunoradiometric assay for circulating intact human BGP (N-tact Osteo SP) by measuring this protein in a large number of normal subjects and patients with the most common metabolic bone diseases. One hundred normal subjects were studied in order to obtain our normal ranges (4.9 ± 1.7 ng/ml). The mean values found in 28 patients with primary hyperparathyroidism (17.5 ± 22.8 ng/ml, P < 0.001), 15 glucocorticoid-treated patients (1.9 ± 1.5, P < 0.001), 10 patients with hypoparathyroidism (1.5 ± 0.7, P < 0.001), 9 with hyperthyroidism (8.3 ± 3.8, P < 0.001), 8 with skeletal metastases (7.2 ± 2.3, P < 0.001), and 4 with humoral hypercalcemia of malignancy (2.42 ± 1.91, P < 0.005) were significantly different from mean values found in normal subjects. Mean decrease of serum osteocalcin T-score values was significantly greater when evaluated by N-tact Osteo SP assay in 15 steroid-treated patients (−1.4 ± 1.0) and 19 primary hyperparathyroid (PHPT) patients (3.6 ± 1.9), compared with the mean values obtained with the Elsa-Osteo assay (−0.67 ± 1.2, P < 0.002 and 4.3 ± 2.8, P < 0.04, respectively). We found significant correlations between the global skeletal uptake of 99mTc-methylendiphosphonate and serum BGP levels assayed by both N-tact Osteo SP (P < 0.01) and Elsa-Ost-Nat assay (P < 0.05). Our results indicate that this new immunoradiometric assay for the intact human osteocalcin has the potential for good discrimination between normal subjects and patients with both low and high bone turnover. Furthermore, our findings emphasize the fact that, in the absence of available standardized commercial assays, one should rely on only one assay because different results are obtained by different assays under different clinical conditions. Received: 22 January / Accepted: 22 September 1998     

Parieto-occipital hypoperfusion in late whiplash syndrome: first quantitative SPET study using technetium-99m bicisate (ECD)

Brain single-photon emission tomography (SPET) withN,N-1,2-ethylene-diylbis-l-cysteine diethyl ester dihydrochloride (ECD) was performed on ten patients with a clinically high grade late whiplash syndrome and on 11 controls. Two independent readers blinded to the clinical diagnosis were able to separate the ten patients from normal controls. All these patients had qualitative bilateral parieto-occipital hypoperfusion. To confirm this, the perfusion rate of parieto-occipital over global (perfusion index) was calculated after drawing elliptical regions of interest in transversal-oblique slices. The perfusion indices in patients were significantly lower than in controls as tested by the Mann-WhitneyU test. This quantitative study proves our recent qualitatively analysed observation (Lancet 1995; 345: 1513–1514).     

Regional myocardial motion and thickening assessed at rest by ECG-gated99mTc-MIBI emission tomography and by magnetic resonance imaging

We have validated ECG-gated emission tomography using technetium-99m methoxyisobutylisonitrile for the assessment of regional ventricular function by comparing it with cine magnetic resonance imaging (MRI). Gated tomography was performed at rest in 24 patients referred for myocardial perfusion imaging [17 males and seven females with a mean age of 58 years, nine of whom had had a previous myocardial infarction (MI)]. Scores were assigned to each of nine myocardial segments for wall motion and for thickening. Cine MRI was analysed in an identical fashion. Four out of 216 (2%) segments were uninterpretable by gated tomography because of inadequate tracer uptake. In eight patients without coronary artery disease (CAD), wall motion and thickening were normal by both methods. Gated tomography showed abnormal wall motion or thickening in all patients with previous MI and in five of seven patients with CAD but no prior MI. Association between wall motion and thickening was good (r _s=0.86). Overall, there was good agreement between gated tomography and MRI for both wall motion (178/212 segments, =0.66) and wall thickening (184/212 segments, =0.69). In segments with severely reduced perfusion, however, there was poorer agreement (=0.31). Interobserver and intraobserver agreement was high ( from 0.61 to 0.78). Thus, in patients investigated for CAD, there is good overall agreement between gated tomography and MRI but the agreement is lower in segments with severe perfusion defects.     

Comparative study of rest technetium-99m sestamibi SPET and low-dose dobutamine stress echocardiography for the early assessment of myocardial viability after acute myocardial infarction: importance of the severity of the infarct-related stenosis

Rest technetium-99m sestamibi single-photon emission tomography (SPET) has been shown to under-estimate viability in some patients with chronic ischaemic myocardial dysfunction. The present study was designed to appraise the value of^99mTc-sestamibi as a viability tracer in patients with a recent myocardial infarction and to determine factors that might influence its accuracy in assessing infarct size. Therefore, rest^99mTc-sestamibi SPET, low-dose dobutamines stress echocardiography and quantitative coronary angiography were performed in 51 patients with a recent myocardial infarction. Perfusion activity and regional wall motion were scored semi-quantitatively using the same segmental division of the left ventricle. Assessment of^99mTc-sestamibi uptake as a marker of viability was performed by comparing a binary uptake score (viable=>50% vs necrotic =50% of the maximal tracer activity) with a binary wall motion classification during low-dose dobutamine infusion (viable=normal/hypokinetic vs necrotic=akinetic/dyskinetic). Infarct size, expressed as the number of segments with evidence of necrotic tissue, was significantly greater in the scintigraphic study than in the echocardiographic study (2.8±1.5 vs 2.2±1.3,P=0.006). This overestimation of infarct size by^99mTc-sestamibi was present only in patients with a severe infarct-related stenosis (% diameter stenosis 65%–100%) and particularly those with late reperfusion therapy (time delay 180 min). In patients without a severe infarct-related stenosis,^99mTc-sestamibi was able to accurately distinguish viable from necrotic segments. Thus, rest^99mTc-sestamibi scintigraphy early after acute myocardial infarction may underestimate residual viability within the infarct region, particularly in patients with low flow state coronary anatomy, as a result of a severe infarct-related stenosis and/or late reperfusion therapy.This paper was presented in part at the European Nuclear Medicine Congress, Brussels, Belgium, August 1995     

Quantitative exercise technetium-99m tetrofosmin myocardial tomography for the identification and localization of coronary artery disease

The aim of this study was to evaluate the accuracy of quantitative 1-day exercise-rest technetium-99m tetrofosmin tomography in the identification of patients with coronary artery disease (CAD) and in the detection of individual stenosed coronary vessels. Sixty-one patients with suspected CAD who underwent coronary angiography and 13 normal volunteers were studied. All patients were submitted to two i.v. injections of^99mTc-tetrofosmin, one at peak exercise (370 MBq) and the other (1110 MBq) at rest 3 h after exercise (images 15–30 min after injection for both studies). All patients with CAD (0% luminal stenosis) (n=50) had an abnormal^99mTc-tetrofosmin tomogram. Only one patient without significant coronary narrowing showed abnormal findings. Overall sensitivity, specificity and diagnostic accuracy in the detection of individual stenosed vessels were 77%, 93% and 85%, respectively. Sensitivity and diagnostic accuracy in the identification of individuals stenosed coronary vessels were significantly higher (P<0.05) in patients with single-vessel disease (n=21) than in those with multivessel disease (n=29). Sensitivity, specificity and accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=26) and in those with previous myocardial infarction (n=35). In myocardial territories related to non-infarcted areas (n=128), sensitivity and specificity in the detection of stenosed vessels were 70% and 95%, respectively. In infarcted areas (n=55), sensitivity and specificity in the detection of stenosed vessels were 85% (P=NS vs non-infarcted areas) and 75% (P<0.05 vs non-infarcted areas), respectively. Finally, sensitivity was significantly lower (P<0.05) in vascular territories supplied by vessels with moderate stenosis (50%–75%) than in those supplied by vessels with severe stenosis (>75%). The results of this study demonstrate that quantitative 1-day exercise-rest^99mTc-tetrofosmin single-photon emission tomographic imaging is a suitable and accurate technique to identify patients with CAD and to detect individual stenosed coronary vessels.     

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。