关于放射免疫治疗的新思考

尽管过去十多年间放射免疫治疗（ＲＩＴ）对实体性肿瘤的临床和实验结果不理想，近年来新的方法和认识可能对ＲＩＴ的应用有进一步的促进。ＲＩＴ的改进主要体现在以微小病灶为主，多次给药，与其他技术配合，免疫调节，以及从肿瘤，机体的生物学特征和放射生物学角度进行Ｔ／ＮＴ比，ＭｃＡｂ瘤内存留时间，细胞这因素，放射剂量的空间与时间分布及肿瘤微环境和宿主体内因素利用等方面的改善和重视，ＲＩＴ的生命力体现在上述方面的     

荷人结肠癌裸鼠瘤内注射^188Re—C50放射免疫治疗实验研究

目的 评价直接法^188Re标记抗CEA单克隆抗体C50和荷人结肠癌裸鼠瘤内注射^188Re－C50放射免疫治疗效果。方法 室温条件下,取4mg维生素C还原C50,0．5h后加入氯化亚锡0．2mL和新鲜淋洗的^188Re370－740MBq,混匀后反应2h以完成整个标记过程。荷人结肠癌裸鼠瘤内分别注射不同剂量的^188Re－C50,观察其治疗作用,并与瘤内注射生理盐水组和^188Re淋洗液组进行比较。结果 标记单抗经放化纯检测,标记液中游离^188Re和胶体^188Re分别少于5％和10％。与对照组比较,瘤内注射14．06MBq以上的标记单抗,其肿生长体积或质量受到明显抑制,甚至体积缩小。结论 直接法^188Re标记C50取得预期结果;瘤内注射^188Re－C50对肿瘤生长有明显的治疗作用。     

^90Y标记单克隆抗体导向治疗肿瘤

论述了＾９０Ｙ的核性质和化学性质特点，＾９０Ｙ标记单克隆抗体的方法的选择，进行肿瘤导向治疗实验研究进展和应用效果，提出了存在的问题及其对策。     

放射免疫治疗中载体的研究进展

放射免疫治疗是应用肿瘤细胞表面表达的特异性分子的单克隆抗体进行核素靶向治疗的一种新方法。通过改进放射性核素的载体,放射免疫治疗的技术不断发展、成熟,其应用范围不断扩展,在未来的疾病定位诊断及治疗中具有很高的应用价值。     

肿瘤放射增敏药物的研究进展

放射治疗是临床肿瘤治疗的重要手段之一.肿瘤细胞的放射敏感性是影响肿瘤放疗疗效的关键因素.放射增敏药物能够增强机体的放射敏感性,通过提高肿瘤细胞的放射敏感性达到降低照射剂量、提高放疗疗效、降低正常组织损伤的目的.现有的放射增敏药物主要分为细胞毒类药物、靶向药物以及中药制剂3大类.该文将对肿瘤放射增敏药物的作用机制、现状及相关研究进展进行综述.     

^90Y在肿瘤治疗中的应用

成功的肿瘤治疗应在减慢肿瘤生长和扩散的同时，较少或不损伤正常组织，＾９０Ｙ作为一种治疗肿的放射性核素，通过标记单克隆抗体，玻璃微球等多种途径，在肿瘤的放射免疫治疗，肝癌的动脉栓塞治疗及瘤内直接注入注射性核素等治疗方法中得到了广泛的应用。     

ZevalinTM：一种放射免疫治疗新药

放射免疫治疗是放射性核素治疗的重要组成和研究的重点之一。Zevalin~(TM)第一个得到FDA批准的用于治疗复发或顽固性低度恶性非霍奇金氏淋巴瘤的放射免疫治疗制剂。本文综述了该制剂的组成、治疗方案、药理作用机制、辐射剂量和临床试验结果等方面的内容。     

131Ⅰ-rituximab治疗B细胞非霍奇金淋巴瘤

放射免疫治疗是将单克隆抗体(单抗)耦联放射性核素,在肿瘤局部产生足够的电离辐射生物学效应,达到高效、低毒的治疗效果.非霍奇金淋巴瘤(NHL)是最常见的淋巴系统恶性肿瘤之一,其绝大多数是B细胞来源,细胞分化抗原CD20是放射免疫治疗B细胞NHL的最佳靶点,用131Ⅰ标记rituximab(一种抗CD20单抗)在治疗B细胞NHL的临床研究中显示出良好的效果,但仍存在许多问题,人们正在进一步研究解决此类问题,以取得更好的治疗效果.     

经典Wnt通路与肿瘤放射抗性关系的研究进展

放疗是治疗恶性肿瘤的重要手段,放射抗性是影响放疗疗效的重要因素,也是放疗失败的主要原因之一。近年来经典Wnt信号通路与肿瘤放射抗性的关系,逐渐受到学者的关注。本文检索了近10年来有关经典Wnt信号通路与肿瘤放射抗性的相关研究,并进行综述,对经典Wnt信号通路参与放射抗性形成的分子机制及功能进行系统分析和梳理,力求寻找某些规律和不同作用途径的内在联系,为进一步深入研究寻找有价值的线索。     

肿瘤乏氧与放射基因治疗

氧效应决定了乏氧细胞的辐射抗性，人的实体肿瘤都有不同程度的乏氧现象，从而成为影响放疗效果的重要因素之一。为改善肿瘤放疗效果，放射增敏剂成为放射生物学的重要研究课题之一。但半个世纪以来，所研发的有效制剂，多止步于或处于临床试验阶段，尚无一药物应用于临床。在此历程中，放射增敏研究在哲学思考和研究策略上也发生变     

188Re-C50对结肠癌细胞的凋亡诱导作用

目的　观察1 88Re 抗癌胚抗原 (CEA)单克隆抗体 (简称单抗 )C5 0放射免疫治疗 (RIT)对结肠癌细胞的凋亡诱导作用。方法　BALB c小鼠结肠癌模型分为治疗与对照组 ,每组 8只。治疗组每只瘤内注射 18 5MBq1 88Re C5 0 ,对照组每只瘤体内局部注射 0 16mgC5 0。 6h后取新鲜肿瘤组织制备肿瘤单细胞悬液 ,采用流式细胞仪 (FCM)行倍体与S期细胞比例检测 ;取肿瘤组织固定后行透射电镜观察与原位末端标记法 (TUNEL)检测。结果　RIT治疗后 6hC2 6结肠癌细胞在用碘化丙啶 (PI)染色的FCM直方图上出现典型凋亡峰 ,C2 6细胞凋亡百分比为 (16 6 4± 0 12 ) % ,对照组为 0 %。肿瘤S期细胞占 (10 4 1± 1 31) % ,对照组为 (33 14± 2 0 1) %。肿瘤G0 G1 期细胞占 (6 8 6 0± 4 82 ) % ,对照组为 (35 12± 2 6 3) % ,治疗后G1 期细胞呈明显阻滞现象。TUNEL检测肿瘤细胞出现凋亡改变 ,凋亡指数 (AI)为 (2 6 4± 0 97) % ,对照组无凋亡改变发生。电镜下癌细胞出现典型的凋亡细胞形态学改变。结论　诱导结肠癌细胞凋亡是1 88Re C5 0抗肿瘤效应的重要作用机理。     

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.     

荷人结肠癌裸鼠瘤内注射~(188)Re-C50放射免疫治疗实验研究

目的　评价直接法188Re标记抗CEA单克隆抗体C5 0和荷人结肠癌裸鼠瘤内注射188Re C5 0放射免疫治疗效果。方法　室温条件下 ,取 4mg维生素C还原C5 0 ,0 5h后加入氯化亚锡 0 2mL和新鲜淋洗的188Re 370～ 740MBq ,混匀后反应 2h以完成整个标记过程。荷人结肠癌裸鼠瘤内分别注射不同剂量的188Re C5 0 ,观察其治疗作用 ,并与瘤内注射生理盐水组和188Re淋洗液组进行比较。结果　标记单抗经放化纯检测 ,标记液中游离188Re和胶体188Re分别少于 5 %和 10 %。与对照组比较 ,瘤内注射 14 0 6MBq以上的标记单抗 ,其肿瘤生长体积或质量受到明显抑制 ,甚至体积缩小。结论　直接法188Re标记C5 0取得预期结果 ;瘤内注射188Re C5 0对肿瘤生长有明显的治疗作用     

Monte Carlo simulations of dose distributions with necrotic tumor targeted radioimmunotherapy

Radio-resistant hypoxic tumor cells are significant contributors to the locoregional recurrences and distant metastases that mark failure of radiotherapy. Due to restricted tissue oxygenation, chronically hypoxic tumor cells frequently become necrotic and thus there is often an association between chronically hypoxic and necrotic tumor regions. This simulation study is the first in a series to determine the feasibility of hypoxic cell killing after first targeting adjacent areas of necrosis with either an α- or β-emitting radioimmunoconjugate.     

Perspectives of molecular imaging and radioimmunotherapy in lymphoma

Successful treatment of Hodgkin lymphomas and non-Hodgkin lymphomas depends on accurate staging and prognostic estimations, as well as evaluation of response to therapy as early after initiation as possible. We focus on several aspects of molecular imaging and therapy that affect the management of patients who have lymphoma. First, we review prior use of gallium-67 citrate for evaluation of lymphoma patients, mainly from a historical perspective, since it was the mainstream lymphoma functional imaging tracer for decades. Next, we review current clinical uses of 18F Fluoro-2-Deoxyglucose (18F FDG) PET and PET/CT for evaluation of lymphoma patients and use of radioimmunotherapy in lymphoma. Finally, we discuss advances in molecular imaging that may herald the next generation of PET radiotracers after 18F FDG.     

Cancer radioimmunotherapy with alpha-emitting nuclides

In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with -emitters for the treatment of refractory cases. The development of novel RIT with -emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of -particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with -emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of -emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an -emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with -emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of -emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.     

Application of the linear-quadratic model to myelotoxicity associated with radioimmunotherapy

The purposes of this study were: (1) to use the linear-quadratic model to determine time-dependent biologically effective doses (BEDS) that were delivered to the bone marrow by multiple infusions of radiolabeled antibodies, and (2) to determine whether granulocyte and platelet counts correlate better with BED than administered radioactivity, which does not take stem cell repopulation, i.e., time, into consideration. Twenty patients with B-cell malignancies that had progressed despite intensive chemotherapy and who had a significant number of malignant cells in their bone marrow were treated with multiple 0.7–3.7 GBq/m² (18–100 mCi/m²) intravenous infusions of Lym-1, a murine monoclonal antibody that binds to a tumour-associated antigen, labeled with iodine-131. Granulocyte and platelet counts were measured in order to assess bone marrow toxicity. BEDs were calculated according to the formula: BED=D(1+gD/(,/))–0.693(T _n–T _k/T _p, whereD represents the absorbed dose of radiation delivered to the red marrow by penetrating emissions of¹³¹I throughout the whole body and nonpenetrating emissions of¹³¹I in the blood and bone marrow,g is a factor that depends on the duration of irradiation relative to the repair half-life of human bone marrow, is the coefficient of nonrepairable damage per Gy, is the coefficient of repairable damage per Gy²,T _n is the time required to reach the granulocyte or platelet count nadir after an¹³¹I-Lym-1 infusion,T _k is the time at which bone marrow proliferation begins after the start of treatment andT _p is the doubling time of the bone marrow after the granulocyte or platelet count nadir has been reached. The cumulative¹³¹I-Lym-1 radioactivity administered to each patient was calculated. Biologically effective doses from multiple¹³¹I-Lym-1 infusions were summated in order to arrive at a total BED for each patient. There was a weak association between granulocyte and platelet counts and radioactivity (the correlation coefficients were –0.23 and –0.60, respectively). Likewise, there was a weak association between granulocyte and platelet counts and BED (the correlation coefficients were –0.27 and –0.40, respectively). The attempt to take bone marrow absorbed doses and overall treatment time into consideration with the linear-quadratic model did not produce a stronger association than was observed between peripheral blood counts and administered radioactivity. The association between granulocyte and platelet counts and BED may have been weakened by several factors, including variable bone marrow reserve at the start of¹³¹I-Lym-1 therapy and the delivery of heterogeneous absorbed doses of radiation to the bone marrow.     

放射免疫治疗中的α核素微剂量研究

微剂量研究在临床α核素放免治疗的计划设计和疗效评价中起重要作用。设计一整套既能准确描述α粒子在细胞、亚细胞水平上剂量的不均匀分布,又适于临床使用的微剂量估算模型,一直是该领域的重要研究内容。本文介绍了α核素微剂量计算的几种常用方法以及最新发现的显著影响其结果精确度的因素。     

放射免疫导向治疗真菌感染灶的研究

由于广谱抗生素、皮质类同醇和免疫抑制剂的广泛应用,可能会导致机体免疫力低下,使致病真菌感染的机会增大,寻找更好的抗真菌疗法是医学研究方向之一。电离辐射可以快速有效的杀死微生物,也可以抗真菌。研究表明,通过特异性抗体标记的靶向放射免疫治疗方法将可能成为抗真菌的一种有效治疗途径。