In vivo molecular targeted radiotherapy

Unsealed radionuclides have been in clinical therapeutic use for well over half a century. Following the early inappropriate clinical administrations of radium salts in the early 20th century, the first real clinical benefits became evident with the use of (131)I-sodium iodide for the treatment of hypothyroidism and differentiated thyroid carcinoma and (32)P-sodium phosphate for the treatment of polycythaemia vera. In recent years the use of bone seeking agents (89)Sr, (153)Sm and (186)Re for the palliation of bone pain have become widespread and considerable progress has been evident with the use of (131)I-MIBG and (90)Y-somatostatin receptor binding agents. Although the use of monoclonal antibody based therapeutic products has been slow to evolve, the start of the 21st century has witnessed the first licensed therapeutic antibody conjugates based on (90)Y and (131)I for the treatment of non-Hodgkin's lymphoma. The future clinical utility of this form of therapy will depend upon the development of radiopharmaceutical conjugates capable of selective binding to molecular targets. The availability of some therapeutic radionuclides such as (188)Re produced from the tungsten generator system which can produce activity as required over many months, may make this type of therapy more widely available in some remote and developing countries.Future products will involve cytotoxic radionuclides with appropriate potency, but with physical characteristics that will enable the administration of therapeutic doses with the minimal need for patient isolation. Further developments are likely to involve molecular constructs such as aptamers arising from new developments in biotechnology.Patient trials are still underway and are now examining new methods of administration, dose fractionation and the clinical introduction of alpha emitting radiopharmaceutical conjugates. This review outlines the history, development and future potential of these forms of therapy.     

Measurement of left-ventricular volumes using an internal standard

When performing equilibrium radionuclide angiocardiography with two successive acquisition views, absolute left-ventricular volumes can be calculated using an internal standard generated by a computer in the left-ventricular cavity. The method is based on the computed ratio of maximum to global activity in the 40°-left-anterior-oblique view after background correction and on the measured depth of the left ventricle in almost-orthogonal, 30°-left-posterior-oblique Fourier first-harmonic images. The method does not require blood sampling or correction for self attenuation. The intra- and interobserver reproducibility is excellent, even in patients with severe impairment of the ventricular-contractility pattern. When compared with a classical method requiring venous-blood counting and an attenuation correction factor, the accuracy of the internalstandard method was fairly good, with a regression coefficient of 0.90.     

2018—2020年参加全国放射性核素γ能谱考核结果分析

目的 保证γ放射性核素实验室活动和结果的有效性,提高实验室γ放射性核素检测的能力。方法 对影响全国γ放射性核素考核结果的相对偏差、准确度、精确度、相对合成不确定度进行统计分析。结果 本实验室2018—2020年全国γ放射性核素考核上报结果均满足合格要求,其中2019年被评为优秀,2018—2020年11个测量结果相对偏差最大为18.01%,2018年|Z_检验|≤1、U_检验≤2.58,2019年|Z_检验|≤1、U_检验≤1,2020年U_检验≤1、U_rel≤20%。结论 本实验室采用的放射性核素γ能谱分析方法正确,检测数据准确、可靠。     

核素三相骨显像在骨缺损移植修复中的价值

目的评价放射性核素三相骨显像在骨缺缺损移植修复过程中的价值.方法试验动物前肢分为骨形态形成蛋白(BMP)和纤维蛋白粘和剂(FS)复和物组(A)、FS组(B)和空白组(C),于术后1、2、4、8周分别行99mTc-MDP三相骨显像和组织学检查,并把所得结果进行比较.结果三相骨显像A组呈持续高灌注、高摄取,B、C组则在第1、2周为高灌注,而后渐下降.各时间段摄取比组间比较AvsB、AvsC P＜0.001,BvsC术后2周P＜0.05,术后第4、8周P＞0.05.组织学检查与骨显像结果吻合良好.结论三相骨显像是骨缺损修复过程中的一种理想监测方法.     

粉防己碱对兔瘢痕组织作用的实验研究

目的 :研究粉防己碱对兔病理性瘢痕的组织学作用 ,为瘢痕治疗提供一种新方法。方法 :采用兔耳腹侧瘢痕模型 ,用粉防己碱 5 0mg /ml、粉防己碱 10mg /ml、去炎松 40mg /ml及生理盐水分别注入瘢痕组织 ,图像分析瘢痕组织中成纤维细胞数量和胶原含量的变化。结果 :粉防己碱治疗组瘢痕组织中成纤维细胞数量与胶原含量均明显减少 ,呈剂量效应关系 ;与生理盐水对照组比较 ,有极显著差异 (P <0 .0 1) ;与去炎松对照组比较无显著差别 (P >0 .0 5 )。结论 :粉防己碱抑制瘢痕组织中成纤维细胞增殖 ,并使胶原合成减少 ,从而抑制瘢痕组织生长 ,有望成为防治病理性瘢痕的新药物     

The continuing important role of radionuclide generator systems for nuclear medicine

In this review, the continuing importance and status of development of radionuclide generator systems for nuclear medicine are discussed. Radioisotope costs and availability are two important factors, and both nuclear reactors and accelerator facilities are required for production of the parent radioisotopes. Radionuclide generator research is currently focused on the development of generators which provide radioisotopes for positron emission tomography (PET) applications and daughter radioisotopes for various therapeutic applications which decay primarily by particle emission. Generator research continues to be influenced by developments and requirements of complementary technologies, such as the increasing availability of PET. In addition, the availability of a wide spectrum of tumor-specific antibodies, fragments, and peptides for radio-immunodiagnosis and radioimmunotherapy has stimulated the need for generator-derived radioisotopes. The advantages of treatment of arthritis of the synovial joints with radioactive particles (radiation synovectomy) may be expected to be of increasing importance as the elderly population increases, and many of these agents are prepared using generator-derived radioisotopes such as yttrium-90 and rhenium-188. Therapeutic use of the in vivo generator is a new approach, where the less radio-toxic parent radioisotope is used to prepare tissue-speciic therapeutic agents. Following in vivo site localization, decay of the parent provides the daughter for therapy at the target site. The principal foundation of most diagnostic agents will continue to require technetium-99m from the molybdenum-99/technetium-99m (Moly) generator. With the limited availability of nuclear reactors and facilities necessary for production and processing of fission ^99mTc and the significant issues and problems associated with radioactive waste processing, however, the possibility of utilizing lower specific activity ⁹⁹Mo produced from neutron activation of enriched ⁹⁸Mo may become practical in the future. Correspondence to: RE Knapp, Jr.     

Assessment of left ventricular function: comparison between radionuclide angiography and semiquantitative two-dimensional echocardiographic analysis

Measurement of global left ventricular function is important in the follow-up of cardiac patients and is a good prognostic indicator in acute cardiac situations. We compared quantitative measurements of global left ventricular function made with radionuclide angiography (RNA) and contrast cardiac ventriculography (CVG) to visual semiquantitative estimates from two-dimensional echocardiographic images (2D-echo). Three hundred and thirty-nine consecutive patients who underwent RNA were assessed with 2D-echo within 3 months. In addition, 92 of these patients also underwent CVG (correlation of ejection fraction between CVG and RNA:r=0.82;P<0.0001). The RNA mean ejection fractions in the four 2D-echo groups (0=normal, 1=slightly, 2=moderate, or 3=severe reduced left ventricular function) differed markedly (P<0.0001); however, there was overlapping among the groups (2D-echo score/RNA ejection fraction: 0=57.3%±12.8%; 1=46.0%±12.9%; 2=29.6%±12.2%; and 3=24.6%±11.5%) and the difference between 2D-echo scores 2 and 3 was not significant. 2D-echo showed a good concordance in RNA classes (0=505; 1=35%–49%; 2=21%–34%; and 3=520% ejection fraction) 0 (133/166; 80%) and 3 (18/30; 60%) but low concordance in classes 1 (27/82; 33%) and 2 (21/61; 34%). For accurate assessment of global left ventricular ejection fraction, visual semiquantitative judgement of a 2D echocardiographic image is limited in comparison to CVG or RNA, especially in patients with a slight or moderate reduction in left ventricular ejection fraction.     

Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

Using single-photon emission tomography (SPET), the radiopharmaceuticall,-3-iodine-123--methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.     

Value of a radionuclide limb blood flow technique in the assessment of percutaneous balloon and dynamic angioplasty

In a prospective study, a radionuclide technique was used to evaluate the limb blood flow (LBF) changes in 30 patients undergoing dynamic (n=15) or balloon (n=15) angioplasty for arterial occlusions or stenoses, respectively. The results were compared with Doppler Ankle Brachial Index (DABI) and treadmill exercise tests. Whilst LBF values (ml of blood flow per 100 ml of limb volume per min) were significantly lower in limbs with arterial occlusion than stenosis (4.5±0.46 and 6.4±0.74, respectively; P<0.05), DABI provided no discrimination. Immediately after balloon angioplasty, there was a fall in DABI, from 0.60±0.05 to 0.47±0.04 (P<0.05), which rose 24 h later to 0.73±0.02 (P<0.01). Following dynamic angioplasty, DABI improved from 0.60±0.05 to 0.66±0.02 (P<0.05). At 3 weeks, the LBF improved from 4.6±0.66 to 11.1±0.53 (P<0.001) following dynamic angioplasty and from 6.2±0.68 to 8.53±0.81 (P<0.001) following balloon angioplasty. Normal LBF (> 10 ml/100 ml per min) was achieved in 80% of patients who underwent successful dynamic angioplasty but in only 36% of the balloon group (P<0.05, ²-test). Reproducibility of repeated LBF measurements in control limbs was superior to that of DABI. This was indicated by a lower coefficient of variation, 13.8% compared with 25.2%, and a higher correlation coefficient, r=0.79 compared with 0.27. Treadmill exercise tests were invalid or impossible in 30% of all occasions. There was a good correlation between the improvement in maximum walking distance on the treadmill and that in LBF (r=0.84, P<0.05). In conclusion, measurement of LBF using radionuclide technique is a potentially valuable method for the assessment of patients undergoing percutaneous angioplasty. LBF results are reproducible and correlate well with the improvement in walking ability, which cannot always be assessed objectively. Offprint requests to: A.A. Gehani     

The clinical utility of provocative radionuclide oesophageal transit in the evaluation of non-cardiac chest pain

We combined edrophonium provocative testing with the technique of radionuclide oesophageal transit (RET) in 30 consecutive patients with non-cardiac chest pain (NCCP) and 12 controls. The oesophageal transit time of aqueous technetium-99m sulfur colloid was determined before and after intravenous infusion of 80 g/kg edrophonium chloride (ED). Patient symptoms during provocative RET (P-RET) were recorded. Thirteen (43%) of the patients had abnormal study results, whereas all control subjects had normal results. Three groups considered abnormal were observed: (a) in two patients (6%), the pain was reproduced and transit pre- and post-ED administration was prolonged (>15 s); (b) in six patients (20%), the pain was reproduced, but transit was normal pre- and post-ED; (c) in five patients (17%), transit pre- and post-ED was prolonged, but no pain was reproduced. In five patients (17%), ED prolonged the transit time > 15 s without pain, but the baseline transit was normal. Transit time was measurable in 23 patients. Mean pre-ED transit time was 10.2 ± 7.4 s (mean ± SD) and post-ED, 12.4 ± 8.0 s (P=0.3). We conclude that ED has no significant effect on transit time, and the pain induced by ED rarely correlates with an abnormal transit; P-RET provides additional information to baseline RET, increasing sensitivity, and may be a useful screening method in the evaluation of patients with NCCP.