肿瘤反义显像技术中的若干问题

反义显像是用放射性核素标记人工合成的反义寡核苷酸，经体内核酸杂交而显示特异基因表达或过度表达的组织。反义显像具有不引起免疫反应、探针分子小、易进入瘤组织等优点。反义显像要求标记的反义核酸易于透过细胞膜、在细胞内稳定、不易分解、并能特异性聚集于靶组织。因此，须对反义寡核苷酸进行化学修饰，增强其细胞通透性和膜内稳定性；利用受体或脂质体介导使反义寡核苷酸定向导入靶细胞；选择合适的放射性核素采用标记简单、标记率高、非特异性结合低且不影响反义寡核苷酸生物活性的标记方法，使其合乎显像要求。成功的反义显像对肿瘤的诊断具有重要意义。     

反义显像技术的研究

反义显像是利用放射性核素标记的反义寡核苷酸,通过体内核酸杂交而显示目的基因表达的一种显像方法,具有设计简便,合成简易,安全性高,免疫原性低等特点,成功的反义显像要求反义寡核苷酸易被细胞摄取,耐酸酶,杂交稳定,标记简单,脂质体,受体等介导的反义RNA转移,反义寡核苷酸的化学修饰以及标记方法的改进将大大加快反义显像的临床应用。     

反义显像技术的研究进展

反义显像是利用放射性核素标记的反义寡核苷酸 ,通过体内核酸杂交而显示目的基因表达的一种显像方法 ,具有设计简便、合成简易、安全性高、免疫原性低等特点。成功的反义显像要求反义寡核苷酸易被细胞摄取、耐核酸酶、杂交稳定、标记简单。脂质体、受体等介导的反义 RNA转移 ,反义寡核苷酸的化学修饰以及标记方法的改进将大大加快反义显像的临床应用。     

肿瘤反义显像技术中的若干问题

反义显像是用放射性核素标记人工合成的反义寡核苷酸、经体内核酸杂交而显示特异基因表达或过度表达的组织。反义显像具有不引起免疫反应、探针分子小，易进入瘤细胞等优点。反义是要求标记的反义核酸易于透过细胞膜、在细胞内稳定、不易分解、并能特异性聚集于靶组织。因此，须对反义寡核苷酸进行化学修饰，增强其通透性和膜内稳定性；利用受体或脂质体介导使反义寡核苷酸定向导入靶细胞；选择合适的放射性核素采用标记简单、标记率     

碘标记c-myc反义寡核苷酸乳腺癌显像的实验研究

用反义核酸为示踪剂 ,靶组织必须具有特异的或高表达的靶分子 ,即ＤＮＡ/ＲＮＡ。在正常组织中 ,一般基因都是单拷贝的 ,而肿瘤组织中绝大部分细胞都有某种或几种癌基因的扩增和高表达。因此 ,利用反义核酸进行肿瘤显像在理论上是可行的。 1994年 ,Ｄｅｗａｎｊｅｅ等[1]首先报道利用111Ｉｎ标记的ｃ ｍｙｃ反义寡核苷酸探针进行ＢＡＬＢ/ｃ乳腺癌动物模型显像 ,实验结果证实了该方法的准确性和灵敏性。参照该实验和131Ｉ标记反义寡核苷酸的方法[2 ] ,我们研究了12 5Ｉ标记的反义和正义寡核苷酸在正常津白Ⅱ号小鼠和乳腺癌自发瘤模型中的分…     

脂质体介导的99Tcm-反义寡聚核苷酸在荷瘤裸鼠体内分布及显像研究

目的：研究脂质体介导的^99Tc^m-反义寡聚核苷酸在荷瘤裸鼠体内的分布及反义显像诊断结肠癌的可能性,为反义显像和反义治疗的临床应用提供实验依据。方法：制作荷瘤裸鼠模型,每只小鼠尾静脉注射约0.30MBq脂质体包裹的^99Tc^m-反义寡聚核苷酸,于不同时间眼眶静脉采血后处死小, 测定不同组织中及标准源的放射性计数。荷瘤裸鼠尾静脉注入脂质体介导的^99Tc^m-反义寡聚核苷酸（30－90mg),于注射后不同时间显像,观察其在肿瘤组织的浓聚情况,并以脂质体介导的^99Tc^m标记的正义和无义寡聚核苷酸为对照。结果：胃、网状内皮系统和肿瘤组织放射性浓聚较高,其次为心和血,余组织中放射性分布较少。肿瘤组织中放射性在2h时达到高峰,以后迅速降低。在2h时,脂质体介导的^99Tc^m-反义寡聚核苷酸能清晰显示肿瘤部位,而对照组则不能。结论：脂质体介导的^99Tc^m-反义寡聚核苷酸可用于结肠癌的诊断,但临床应用前还需进行大量的研究。     

反义显像技术在肿瘤诊断中的应用

反义显像技术以放射性核素标记的人工合成的寡核苷酸为显像剂，通过体内核酸杂交而显示特异性癌基因过度表达的癌组织。肿瘤癌基因的特异性、放射性核素的选择以及标记化合物的稳定性、比放射性等诸参数均影响显像效果。成功的反义显像要求寡核苷酸探针具有容易大量合成、体内稳定、能与靶序列结合并且不发生非序列性特异性结合等特点。反义显像以癌基因为基础，使肿瘤显像进入基因水平     

反义显像技术在肿瘤诊断中的应用

反义显像技术以射性核素标记的人工合成的寡核苷酸为显像剂，通过体内核酸交而显示特异性癌基因过度表达的癌组织。     

脂质体介导的99Tcm-反义寡聚核苷酸在荷瘤裸鼠体内分布及显像研究

目的研究脂质体介导的99Tcm-反义寡聚核苷酸在荷瘤裸鼠体内的分布及反义显像诊断结肠癌的可能性,为反义显像和反义治疗的临床应用提供实验依据.方法制作荷瘤裸鼠模型,每只小鼠尾静脉注射约0.30MBq脂质体包裹的99Tcm-反义寡聚核苷酸,于不同时间眼眶静脉采血后处死小鼠,测定不同组织中及标准源的放射性计数.荷瘤裸鼠尾静脉注入脂质体介导的99Tcm-反义寡聚核苷酸(30～90mg),于注射后不同时间显像,观察其在肿瘤组织的浓聚情况,并以脂质体介导的99Tcm标记的正义和无义寡聚核苷酸为对照.结果胃、网状内皮系统和肿瘤组织放射性浓聚较高,其次为心和血,余组织中放射性分布较少.肿瘤组织中放射性在2h时达到高峰,以后迅速降低.在2h时,脂质体介导的99Tcm-反义寡聚核苷酸能清晰显示肿瘤部位,而对照组则不能.结论脂质体介导的99Tcm-反义寡聚核苷酸可用于结肠癌的诊断,但临床应用前还需进行大量的研究.     

核酸及其类似物的常见放射性核素标记及显像

放射性核素标记的核酸及其类似物在基因标记显像和基因治疗药物开发等多方面具有重要意义.该文对常见的放射性核素标记核酸及其类似物的方法和动物显像进行综述,并评述其应用前景.     

The particular usefulness of radioisotope methods in some benign bone diseases.

The authors have performed radioisotope examinations in 271 patients with various non-neoplastic bone diseases. According to their opinion, early diagnosis and follow-up of therapeutic results are the main characteristics which allow radioisotopes to play an important and irreplaceable role. They particularly emphasize the usefulness of radioisotope methods in femoral aseptic necrosis and Paget's disease.     

The particular usefulness of radioisotope methods in some benign bone diseases

The authors have performed radioisotope examinations in 271 patients with various non-neoplastic bone diseases.According to their opinion, early diagnosis and follow-up of therapeutic results are the main characteristics which allow radioisotopes to play an important and irreplaceable role.They particularly emphasize the usefulness of radioisotope methods in femoral aseptic necrosis and Paget's disease.     

A simple and selective method for the separation of Cu radioisotopes from nickel

Separation of copper radioisotopes from a nickel target is normally performed using solvent extraction or anion exchange rather than using cationic exchange. A commonly held opinion is that cationic exchangers have very similar thermodynamic complexation constants for metallic ions with identical charges, therefore making the separation very difficult or impossible. The results presented in this article indicate that the selectivity of Chelex-100 (a cationic ion exchanger) for Cu radioisotope and Ni ions not only depends on the thermodynamic complexation constant in the resin but also markedly varies with the concentration of mobile H+. In our developed method, separation of copper radioisotopes from a nickel target was fulfilled in a column filled with Chelex-100 via controlling the HNO3 concentration of the eluent, and the separation is much more effective, simple and economical in comparison with the common method of anion exchange. For an irradiated nickel target with 650 mg Ni, after separation, the loss of Cu radioisotopes in the nickel portion was reduced from 30% to 0.33% of the total initial radioactivity and the nickel mixed into the radioactive products was reduced from 9.5 to 0.5 mg. This significant improvement will make subsequent labeling much easier and reduce consumption of chelating agents and other chemicals during labeling. If the labeled agent is used in human medical applications, the developed method will significantly decrease the uptake of Ni and chelating agents by patients, therefore reducing both the stress on human body associated with clearing the chemicals from blood and tissue and the risk of various types of acute and chronic disorder due to exposure to Ni.     

Radioactive sputter cathodes for 32P plasma-based ion implantation.

The development of clinical treatments involving the use of beta-emitting millimetric and sub-millimetric devices has been a continuing trend in nuclear medicine. Implanted a few nanometers below the surface of endovascular implants, seeds or beads, beta-emitting radioisotopes can be used in a variety of biomedical applications. Recently, new technologies have emerged to enable the rapid and efficient activation of such devices. A pulsed, coaxial electron cyclotron resonance plasma reactor was designed and tested to demonstrate the feasibility of plasma-based radioactive ion implantation (PBRII). It has been shown that such plasma reactors allow for the implantation of radioisotopes (32P) into biomedical devices with higher efficiencies than those obtained with conventional ion beams. Fragments containing radioactive atoms are produced in the implanter by means of a negatively biased solid sputter cathode that is inserted into an argon plasma. Dilute orthophosphoric acid solutions (H3(32)PO4) are used for the fabrication of flat sputter targets, since they offer a high radioisotope content. However, the aggregation of the radioactive solute into highly hygroscopic ring-like deposits rather than flat, thin radioactive films is observed on certain substrates. This article describes the effect of this nonuniform distribution of the radioisotopes on the efficiency of PBRII, and presents a technique which enables a better distribution of 32P by coating the substrates with iron. The iron coating is shown to enable optimal radioisotope sputtering rates, which are essential in 32P-PBRII for the efficient activation of millimetric biomedical devices such as stents or coils.     

Analysis of metal radioisotope impurities generated in [(18)O]H(2)O during the cyclotron production of fluorine-18.

We show the separation of metal radioisotope impurities using capillary electrophoresis (CE). The methodology used is an improvement of existent protocols for separation of stable metal ions. Production of fluorine-18 using [(18)O]H(2)O-enriched water encased in a titanium target body results in the production of several metal radioisotope impurities. Optimisation of the conditions for CE separation of the metal radioisotope impurities incorporated the use of 6 mM 18-Crown-6 in combination with 12 mM glycolic acid as complexing agents within the running buffer (10 mM pyridine, pH 4.0). Using this optimised procedure, we were able to separate and detect a number of metal radioisotopes, including chromium, cobalt, manganese, vanadium and berillium, within the fM concentration range.     

受体介导的反义治疗研究

受体介导的反义治疗是利用受体与配体高特异性、高亲和力结合的特点,通过受体介导的内吞作用,将配体与反义寡核苷酸(ASON)形成的转运复合物靶向运送到特定的细胞,使细胞内的ASON达到足够高的浓度,从而有效发挥反义抑制作用。本文简要综述对受体介导的反义治疗日前常用的受体、转运复合物的形成、内吞过程中需要解决的问题及实验研究进展。     

Recent developments in the radiolabeling of antibodies with iodine, indium, and technetium

The use of radiolabeled antibodies for tumor detection and therapy has provided some striking successes despite unfavorable tumor-to-normal tissue radioactivity ratios due, in part, to the accumulation of the label in normal tissues. One approach, which has been and is still under consideration to reduce unwanted background levels, is the improvement of ways in which radiolabels are attached to antibody, especially with the goal of increasing in vivo stability. Although these improvements have occurred throughout the history of this field, important developments have recently been reported in the labeling of antibodies with three radiolabels, namely radioiodine, 111In, and 99mTc. Thus, antibodies may now be labeled with radioisotopes of iodine in ways that minimize the extent of in vivo dehalogenation leading to thyroid, stomach, and gut radioactivity uptake. Newer and stronger chelates for 111In have been developed in the hope that their use would result in lower radioactivity levels in the liver. Finally, newer methods, both direct and indirect, for the attachment of 99mTc to antibodies have been developed and are now being clinically tested. Although these developments have taken place only recently and the in vivo behavior of labels attached in these ways have not yet been fully characterized, it is possible to make tentative conclusions regarding their impact. Thus, the use of stably radioiodinated antibodies appears to have resulted in modest improvements in patient images. In contrast, the use of stable chelates for labeling antibodies with 111In may have had no appreciable effect on liver radioactivity levels. The use of antibodies radiolabeled with 99mTc, especially via the newer direct labeling methods, are providing superior images in patients with low radioactivity levels in organs such as liver. However, it must still be established whether the short physical half-life of 99mTc lowers sensitivities and specificities of detection relative to other labels.     

反义技术及其在医药领域中应用的最新进展

反义技术是基因疗法的一种，它为疾病的治疗提供了一条崭新的途径。现已有六种反义制剂进入了临床实验。作者简述了反义技术的原理、在基础研究及医药领域中的应用及寡聚核苷酸真正付诸于应用所需满足的条件。     

A new radioiodine exchange labeling technique

A new technique of radioiodine exchange labeling is presented. The method was developed with respect to the short physical half lives of ¹²³I and ¹²¹I, the altered activity concentrations and varying impurities, which hamper the previously introduced labeling methods. The described “one step reaction” is applicable to a series of organic compounds with different physicochemical and physiological behaviour as well as to all radioisotopes of iodine.