胰腺癌的放射免疫治疗进展

胰腺癌是常见的肿瘤，但预后很差，传统治疗的结果令人失望，放射免疫治疗提供了一个新的治疗途径。单克隆抗体具有高度的特异性，放射性核素在肿瘤部位积聚高而达到杀伤瘤细胞的目的。完整的单抗因其分子质量较大而难于达到肿瘤内部，且易诱发人抗鼠抗体反应。基因工程抗体因具有更高的亲和力和更容易进入肿瘤内部，已成为放射免疫治疗的热点及突破胰腺癌临床治疗的关键所在，将在胰腺癌的治疗中发挥重要作用。     

放射免疫治疗的应用基础研究

放射免疫治疗（RIT）是肿瘤免疫靶向治疗的一种,以特异性抗体为载体,用放射性核素标记,将放射性药物导向肿瘤区,浓聚在靶器官,放射性核素衰变释放出大量射线,从而选择性杀伤癌细胞,其实质上是一种连续低剂量的体内照射治疗,通过诱导肿瘤细胞凋亡和引起细胞凋亡调控基因表达的改变而达到治疗目的。其优点：（1）对肿瘤细胞具有特异性杀伤;     

肿瘤放射免疫疗法研究进展

放射免疫治疗是将针对肿瘤特异抗原的单克隆抗体用核素标记后,对肿瘤细胞进行的靶向治疗。在非霍奇金淋巴瘤的临床治疗中,放射免疫治疗已经成为一种常规的治疗手段。在实体瘤中,因为核素标记的单克隆抗体的定位很有限,所以限制了该疗法的使用。虽然如此,放射性核素标记的抗体在治疗微小病灶中的应用前景看好。     

用于放免治疗的核素研究进展

放射免疫治疗肿瘤具有独特优势,许多新的核素被用于制备肿瘤放免治疗药物.高能α、β粒子及抗肿瘤导向载体的应用促进了放免治疗药物的发展.本文介绍了用于放射免疫治疗的核素最新研究进展,归纳了用于放射免治疗的常用放射性核素,并比较了各自的优缺点,指出了放射性核素用于放射免疫治疗过程中存在的问题、可能的解决方法及今后的发展趋势.     

用于放免治疗的核素研究进展

放射免疫治疗肿瘤具有独特优势，许多新的核素被用于制备肿瘤放免治疗药物。高能α、β粒子及抗肿瘤导向载体的应用促进了放免治疗药物的发展。本文介绍了用于放射免疫治疗的核素最新研究进展，归纳了用于放射免治疗的常用放射性核素，并比较了各自的优缺点，指出了放射性核素用于放射免疫治疗过程中存在的问题、可能的解决方法及今后的发展趋势。     

抗体-链霉亲和素和~(90)Y-DOTA-生物素预定位放射免疫治疗的临床最佳化

目的 :通过初步临床研究 ,了解抗体 -链霉亲和素和 90 Y-DOTA (双功能联结剂 ) -生物素预定位放射免疫治疗方法治疗肿瘤病人的可行性 ,同时获得用于临床治疗肿瘤病人的最佳方案。方法 :43例患有能与 NR- L U- 10鼠源性单抗反应的腺癌病人 ,分别在不同时间接受不同剂量的抗体 -链霉亲和素联结剂 (接有链霉亲和素的 NR- L U - 10鼠源性单克隆抗体 )、清除剂 (生物素化的半乳糖人血清白蛋白 ,为减少循环中的抗体联结剂 )和 90 Y- DOTA-生物素预定位放射免疫治疗 ;对其安全性、肿瘤靶向性、生物学分布、药代动力学、剂量学和免疫源性开…     

PKC抑制剂对人胰腺癌细胞的放射增敏效应

胰腺癌是一种常见的消化系统恶性肿瘤，放射治疗已成为其主要的治疗方法之一。但由于胰腺癌放射敏感性低，严重影响了放射治疗在胰腺癌l临床治疗中的应用。如何提高胰腺癌的放射敏感性，成为胰腺癌放射治疗研究的重点之一。蛋白激酶C（Protein Kinase C，PKC）是重要的细胞内信号传导分子，其过度活化在肿瘤的发生、发展中起着十分重要的作用，已成为肿瘤治疗的靶点。据文献报道白屈菜红碱（Chelerythrine，CH）具有选择性抑制PKCα、β亚型的作用。     

非霍奇金B细胞淋巴瘤的放射免疫治疗进展

单克隆抗体的成功应用 ,使肿瘤的放射免疫治疗 (ｒａｄｉｏｉｍ ｍｕｎｏｔｈｅｒａｐｙ,ＲＩＴ)成为可能。由于大多数非霍奇金淋巴瘤 (ＮＨＬ)是ＣＤ2 0阳性的Ｂ细胞淋巴瘤 ,将具有细胞毒性的放射性核素标记的特异性抗ＣＤ2 0单克隆抗体 ,注入体内后可实现对肿瘤细胞的大剂量内照射 ,而正常组织损伤较小 ,大大提高了治疗的缓解率 ,延长了缓解期。1　概　述放射免疫治疗即利用特异性抗体作载体 ,与能释放β或α射线的放射性核素偶合 ,注入体内与肿瘤细胞特异性结合 ,实现对瘤体的内照射治疗。这种治疗多为静脉给药 ,也可局部给药。放射免疫…     

免疫PET显像在肿瘤诊疗中的研究进展

免疫PET显像是一种新型分子影像模式,其有机结合了单克隆抗体的高特异性与PET显像的高灵敏度。近年来,免疫PET显像探针的临床转化应用日渐增多,其可实现对多种肿瘤的早期无创诊断、抗体治疗患者分层以及放射免疫治疗的精准剂量评估。该文对免疫PET显像在肿瘤诊疗方面的研究进展进行了总结。     

放射免疫显像及其在胰腺癌研究中的应用

肿瘤的放射免疫显像是基于肿瘤抗原与抗体特异性结合的原理,将放射性标记抗体用于肿瘤诊断的显像方法。基因工程技术促进了抗体的发展,产生了多种抗体及其衍生物,推动了放射免疫显像的深入研究。胰腺癌是一种恶性程度较高的肿瘤,其发病隐匿、进展迅速、治疗困难,随着单克隆抗体的研究进展、预定位技术和放射免疫导向手术的应用,胰腺癌放射免疫显像有望成为胰腺癌诊断的重要手段。     

Radioimmunoscintigraphy of pancreatic cancer in tumor-bearing athymic nude mice using (99m)technetium-labeled anti-KL-6/MUC1 antibody

Purpose KL-6 is an extracellular epitope of MUC1, a membrane-penetrating glycoprotein, and its overexpression has been reported in pancreatic cancer. The aim of this study was to examine whether radiolabeled anti-KL-6/MUC1 antibody could be used for molecular imaging of pancreatic cancer in vivo. Materials and methods Anti-KL-6/MUC1 antibody was labeled with ^99mTc by the stannous reduction method. Immunoreactivity of the ^99mTc-labeled anti-KL-6/MUC1 antibody was evaluated by a whole-cell binding study. In vivo experiments were performed by injecting the ^99mTc-labeled anti-KL-6/MUC1 antibody into athymic nude mice bearing the KP-1NL pancreatic cancer cell line. Results A whole-cell binding study showed that the radiolabeled antibody retained its immunoreactivity. On scintigrams, the density of the tumors remained unchanged during the 16–32 h after injection, whereas that of the kidneys decreased time-dependently. The radioactivity levels of the kidneys and tumors were measured densitometrically, and we found that the intensity in the tumors relative to that in the kidneys increased time-dependently. Radioactivity levels were the highest in the blood 32 h after injection, and those in the liver, kidney, lung, and tumor were also rather high. Conclusion ^99mTc-labeled anti-KL-6/MUC1 antibody appears to be a promising agent as a tumor-specific radiotracer for pancreatic cancer.     

免疫光敏剂抗癌作用的动物实验研究

将血卟啉与抗结肠癌单克隆抗体偶联构成免疫光敏剂,静脉注入荷人结肠癌裸鼠体内,同时以注射单纯血卟啉鼠为对照,经激光照射,初步实验结果显示注射免疫光敏剂鼠不仅肿瘤光敏坏死面积大于注射单纯血卟啉鼠,而且坏死程度亦严重而广泛。表明单克隆抗体在动物体内有可能起到将血卟啉导向肿瘤部位的作用,从而较单独应用血卟啉疗效提高。     

EPO单克隆抗体的制备

目的：制备EPO单克隆抗体,为高原红细胞增多症的治疗研究提供材料。方法：用细胞融合技术制备能稳定分泌EPO单克隆抗体的细胞株,对该细胞株扩增培养,注射入BALB小鼠腹腔内,（7～10）天后搜集腹水并进行腹水抗体效价测定,提纯,浓缩,进行抗体浓度测定。结果：得到一株能稳定分泌EPO单克隆抗体的细胞株,并制备出高效价的EPO单克隆抗体。结论：该EPO单克隆抗体的制备成功为高原红细胞增多症的治疗的基础研究提供了原料。     

Multimodal and three-dimensional imaging of prostate cancer.

Accurate characterization of prostate cancer is crucial for treatment planning and patient management. Non-invasive SPECT imaging using a radiolabeled monoclonal antibody, 111In-labeled capromab pendetide, offers advantage over existing means for prostate cancer diagnosis and staging. However, there are difficulties associated with the interpretation of these SPECT images. In this study, we developed a 3D surface-volume hybrid rendering method that utilizes multi-modality image data to facilitate diagnosis of prostate cancer. SPECT and CT or MRI (or both) images were aligned either manually or automatically. 3D hybrid rendering was implemented to blend prostate tumor distribution from SPECT in pelvis with anatomic structures from CT/MRI. Feature extraction technique was also implemented within the hybrid rendering for tumor uptake enhancement. Autoradiographic imaging and histological evaluation were performed to correlate with the in-vivo SPECT images. Warping registration of histological sections was carried out to compensate the deformation of histology slices during fixation to help the alignment between histology and in-vivo images. Overall, the rendered volumetric evaluation of prostate cancer has the potential to greatly increase the confidence in the reading of radiolabeled monoclonal antibody scans, especially in patients where there is a high suspicion of prostate tumor metastasis.     

单克隆抗体人源化技术研究进展

随着分子生物学技术的发展,应用DNA重组技术、抗体库技术及转基因技术对鼠源性单抗进行人源化改造,先后出现了嵌合抗体、互补决定区移植抗体和全人源抗体,它们从不同角度克服了鼠源性单抗临床应用的不足,为单克隆抗体在临床诊断及治疗中的应用带来了新的曙光,该文对单克隆抗体人源化技术的研究进展作一综述。     

EPO单克隆抗体抑制CFU-E研究

目的 探讨EPO单克隆抗体是否具有抑制红系集落形成单位（CFU-E）形成的功能.方法 对大鼠骨髓进行定向体外CFU-E培养,按以下条件进行分组培养：空白对照组（不加EPO）、常规组（加EPO,不加EPO单克隆抗体）、EPO单克隆抗体干预组（EPO＋EPO单克隆抗体）.培养168 h后,观察各组CFU-E数量.结果 空白对照组、常规组、EPO单克隆抗体干预组的CFU-E集数落分别为0.0±0.0、151.8±23.3和10.7±3.9.EPO单克隆抗体干预组与常规组比较,CFU-E集落数存在非常显著性差异（P＜0.01）.结论 该EPO单克隆抗体可明显抑制CFU-E形成,即抑制红细胞系的增殖,是治疗高原红细胞增多症的可能药物.     

单克隆抗体标载的~(131)Ⅰ脑胶质瘤瘤内放免治疗

目的探讨131I-chTNT(131I-肿瘤细胞核人鼠嵌合单抗)通过局部化疗囊注入胶质瘤瘤腔内,行瘤内放免治疗的价值。方法选择全部经手术病理证实的脑胶质瘤56例,其中胶质母细胞瘤34例,星形细胞瘤22例。第1次手术者20例,余为复发性手术。术中瘤腔内置入化疗囊,手术后7d囊内注131I-chTNT1.1×103Bq,15d后重复注入1次。结果于末次注药后2个月复查CT或MRI,随访期6个月～2年2个月,完全缓解21例(37.5%),部分缓解24例(42.8%),临床症状减轻,病情稳定7例(12.5%),病情恶化4例(7.1%)。结论单克隆抗体与131I交联后靶向于肿瘤细胞核,与瘤体特异性结合,并将其荷载的放射性核素输送到肿瘤细胞内,由内向外摧毁肿瘤。临床疗效满意,优于其他类型的瘤内近距离放疗。     

Immunoscintigraphy of human tumors transplanted in nude mice with radiolabeled anti-ras p21 monoclonal antibodies

Anti-ras p21 monoclonal antibody (RASK-3) was used for immunoscintigraphy of human cancer cell lines in nude mice. Iodine-125-labeled RASK-3 was injected into nude mice with either human colon cancers (FCC-1 or BM-314) or lung cancer (KNS-62). Clear images were obtained in all three cancers 7 days after the injection of antibody. No localization of 125I-labeled control monoclonal antibody was observed. The ratio of tissue/blood radioactivity and % ID/g in the tumor were significantly higher than other organs by Day 8. The specific localization index examined by 131I-RASK-3 and 125I-control monoclonal antibody was also higher in the tumor than in other tissues. In the in vitro study, binding of RASK-3 to tumor cells increased significantly by treatment of cells with either lysolecithin or periodate-lysine-paraformaldehyde, which confirmed the intracellular localization of ras p21. The mechanism by which anti-ras p21 antibodies accumulate in tumor sites could be the necrotic changes in tumor cells or changes in membrane permeability of non-necrotic cells. These results provide a strong rationale for the utilization of ras p21 as a target antigen in the imaging of a variety of human cancers.     

Scintigraphic imaging of P-glycoprotein expression with a radiolabelled antibody

Purpose P-glycoprotein (P-gp) is a membrane efflux pump protein that is involved in multidrug resistance (MDR). Tumour cells with high P-gp expression show poor response to cancer treatment with several chemotherapeutics. In vivo targeting and visualisation of P-gp expression would allow MDR to be evaluated non-invasively prior to treatment. The aim of this study was to investigate the feasibility of visualising P-gp expression in tumours using a monoclonal anti-P-gp antibody, 15D3.Methods Nude BALB/c mice with subcutaneously growing human uterine sarcoma cell tumours with either high (MES-SA/D×5 1977) or low (MES-SA 1976) P-gp expression were used. When tumours were 0.2–0.4 g, mice received ¹³¹I-15D3 or ¹¹¹In-DTPA-15D3 monoclonal anti-P-gp antibody intravenously. Images were acquired up to 3 days p.i. and radioactivity concentration in various tissues was determined after euthanisation of the animals.Results The images demonstrated that radioactivity accumulated to a higher concentration in high P-gp expressing tumours than in the low P-gp expressing MES-SA 1976 tumour. Furthermore, visualisation of the P-gp expressing tumours was superior with ¹¹¹In-DTPA-15D3 than with ¹³¹I-15D3. After injection of ¹¹¹In-DTPA-15D3, the high P-gp expressing MES-SA/D×5 1977 tumours were clearly visualised at 3 days p.i. The biodistribution data indicated that radioactivity concentration in the high P-gp expressing tumours was higher than in the tumours with low P-gp expression (20.78±1.42 %ID/g for MES-SA/Dx5 1977 tumours and 8.39±3.78 %ID/g for MES-SA 1976 tumours for ¹¹¹In-DTPA-15D3).Conclusion The ¹¹¹In-labelled monoclonal anti-P-gp antibody clearly visualised P-gp expression in a human uterine sarcoma tumour in nude mice.