131I-BDI-1在荷人膀胱癌裸鼠体内的生物分布研究及辐射剂量评估

目的 探讨131I-BDI-1在荷人膀胱癌裸鼠模型中的体内生物分布和对肿瘤的靶向定位性能以及其生物安全性,并由此估算131I-BDI-1在人体内主要脏器的内照射吸收剂量和人体有效剂量.方法 通过氯胺-T法用131I溶液直接标记抗人膀胱癌单克隆抗体BDI-1,制备131I-BDI-1,荷人膀胱癌EJ细胞裸鼠尾静脉注射222kBq 131I-BDI-1后,于不同时刻处死动物,取感兴趣器官和组织,称重并测量放射性计数,计算131I-BDI-1在荷瘤裸鼠中的标准摄取值和靶/非靶组织比值.利用标准的MIRD数据表计算人体的％ID/g,通过MIRDOSE3.1软件估算131 I-BDI-1对人体各个器官的辐射吸收剂量及有效剂量.结果 生物分布数据示131I-BDI-1血液清除缓慢,肿瘤部位放射性明显持续滞留,除血液外,具有较高的靶/非靶组织比值.131I-BDI-1人体内照射的有效剂量为1.46×10-2 mGy/MBq.结论 131I-BDI-1对肿瘤有良好的靶向性,有望成为一种新型的针对人膀胱癌肿瘤的诊治药物,其辐射吸收剂量较低,作为肿瘤治疗药物是安全的.     

131I致兔甲状腺功能低下模型制作的探讨

目的探讨利用放射性131I制作甲状腺功能低下动物模型的方法和可行性.方法选用纯种新西兰兔随机分为正常对照、低剂量、高剂量三组,用胃管给药法将131I引入动物体内.通过99mTc扫描、甲状腺激素动态测定及病理检查等评价动物模型的甲状腺功能及组织学改变情况.结果各实验组病理生理改变差异显著,高剂量组模型明显甲状腺功能低下改变.结论合适的放射性碘剂量能稳定地制作甲状腺功能低下动物模型.     

131I致兔甲状腺功能低下模型制作的探讨

目的探讨利用放射性131I制作甲状腺功能低下动物模型的方法和可行性.方法选用纯种新西兰兔随机分为正常对照、低剂量、高剂量三组,用胃管给药法将131I引入动物体内.通过99mTc扫描、甲状腺激素动态测定及病理检查等评价动物模型的甲状腺功能及组织学改变情况.结果各实验组病理生理改变差异显著,高剂量组模型明显甲状腺功能低下改变.结论合适的放射性碘剂量能稳定地制作甲状腺功能低下动物模型.     

中华眼镜蛇毒组份J在家兔体内的药代动力学研究

目的 探讨眼镜蛇毒（Naja naja atra venom)组份J兔体内的药代动力学过程。方法 用氯胺-T法对眼镜蛇毒组份J进行^125I标记，以放射性核表示踪动力法检测血液中的药物浓度，药-时数用3P87程序处理，结果与结论 兔静脉注射眼镜蛇毒组份J3个剂量后，药-时曲线经拟合符合三房室模型特征；快分布相半衰期T1/2α为37.4-41.6min，慢分布相半衰期T1/2β为15.3-16.9hr，消除相半衰期T1/2γ为20.9-21.8hr，三个时相的半衰期各剂量组之间无显著性差异。曲线下面积AUC与剂量成正比，表明药物在兔体内的分布和消除为一级线性动力学过程。     

131I-c(RGD)2的药代动力学及急性毒性研究

目的 用131I标记二硫键成环的RGD肽二聚体c(RGD)2,探讨其在裸鼠体内的药代动力学参数、急性毒性反应和死亡情况,评价其应用的安全性.方法 选取5只裸鼠为实验对象,每只经尾静脉注射131I-c(RGD)2(7.4 MBq/200μL),分别于注射后3、6、10、15、30、45、60、120、180及360min断尾取血5μL,测量血液的放射性计数,采用PKSolver软件进行药代动力学分析.另取裸鼠10只随机分为实验组及对照组,实验组每只经尾静脉注射131I-c(RGD)2(7.4 MB/60μL);对照组经尾静脉注射生理盐水60μL,观察注射后72 h内裸鼠的不良反应和死亡情况.结果 血液药-时曲线符合权重系数为1/CC的开放性二房室分布模型,其中分布相半衰期(t1/2α)为15.364 min,消除相半衰期(t1/2β)为123.125 min.注射131I-c(RGD)2后72 h内,裸鼠无不良反应与死亡.结论 c(RGD)2具有理想的药代动力学特点,且无明显毒性作用,这些均有利于其作为新药应用于临床.     

SPARFLOXACIN正常人体耐受性及药代动力学研究

本研究对日产sparfloxacin进行了100mg、200mg、300mg和400mg四个剂量的耐受性试验,100mg、200mg、400mg三个剂量的药代动力学试验。耐受性试验结果表明直至400mg试验结束不论是受试者主观感觉,还是血、尿生化指标均无改变。证明单次口服sparfloxacin 400mg以下可以耐受。药代动力学试验结果表明分别口服100mg、200mg、400mg三个剂量sparfloxacin片剂以后用HPLC法测定血尿药物浓度,计算所得主要药代动力学参数分别为:C_(max)=0.38±0.     

导向药代动力学研究

本文用~(125)I标记导向药物测定其药时曲线和体内分布,提出初步数学模型,计算出其药代动力学参数,并与柔红霉素(DNR)在白血病患者的药代动力学参数进行比较,以评估导向药物在临床应用中的价值。与此同时建立了测定导向药物HI30-PAD-DNR中柔红霉素的水解产物柔红酮(daunomycinone,DNRO)非同位素测定导向药物血药浓度方法。为将来导向药物Ⅰ期和Ⅱ期临床     

氧化苦参碱的药代动力学研究(摘要)

我们给大鼠静脉或肌肉注射13(n)_-~3H—氧化苦参碱。给药后不同时间测定血药浓度并用电子计算机计算不同途径给药时的药代动力学参数。实验用Wisar雄性大鼠,每组4只,体重242.1±17.2克13(n)H—氧化苦参碱比放射性15.6ci/毫克分,子放化纯度99％。临用前加非放射性载体(20mg/ml)配成放射性浓度为100uci/ml的注射液。尾静脉或右后肢肌肉注射。放射性剂量均为25uci/100克体重。静脉注射后5、10、15、20、25、30、40、50、60、70、80、90分钟尾尖取血10ul。肌注后5、10,     

某医院核医学科不同区域不同形态131I的分布研究

目的131I是核医学中使用量较大的人工放射性核素,挥发性强,在人体剂量学中,微粒碘与气态碘对内照射剂量的影响不同,因此研究应用过程中不同形态131I在环境中分布对内照射剂量估算具有重要的意义。方法使用活性炭盒加滤膜分别采集某医院核医学科不同区域内空气中的气态131I和微粒态131I,利用HPGeγ谱仪对采集样品进行测量,获得了不同区域中气态碘和微粒碘的浓度分布。结果给药量为400mCi时核医学科区域中的气态131I浓度范围为5.6×10-1~1.2×102Bq/m3,微粒态131I的浓度范围1.0×10-1~8.9Bq/m3,给药室和病房中微粒与气态131I的比值在0.053~0.659之间,其比值都小于1。结论气态131I相对微粒态131I来说浓度较高,且在核医学科不同区域,该比值差异较大。     

~(131)I-CEA单克隆抗体免疫显像诊断结、直肠癌的研究

本文报道应用~(131)I-CEA McAb在23例结、直肠癌和2例多发性良性结肠息肉病人的免疫显像结果及标记单抗在体内的血液动力学特性。两组单抗C14-17和C50均由卫生部北京生物制品研究所研制,用氯胺T法标记。静注剂量5～8mCi/2mg IgG。血液中放射性的第一半清时C14-17和C50分别为21.6h和26.4h,第二半清时分别为29.6h和40.8h。血液放射性主要存在于血浆中(96％),蛋白结合放射性占95.5％,游离放射性占0.5％,红细胞、白细胞放射     

肝癌单克隆抗体HAb18及其F（ab′）_2、Fab片段在小鼠体内的药代动力学研究

作者对１３１Ｉ标记的抗人肝细胞癌单克隆抗体ＨＡｂ１８及Ｆ（ａｂ′）２、Ｆａｂ片段在小鼠体内的药代动力学进行研究。结果表明：（１）３种标记物的药代动力学模式有很大差异，完整抗体ＨＡｂ１８的清除过程符合开放一空模型，清除速率与注射剂量有关。按照剂量从高至低，其Ｔ１／２（整体排泄）分别为４８．０８ｈ、４２．６５ｈ、４０．５４ｈ；Ｔ１／２（血液清除）依次为６１．４２ｈ、４８．０７ｈ、４１．０３ｈ。（２）抗体片段的清除速率明显快于完整抗体，清除过程呈双相下降，符合二室模型。Ｆ（ａｂ′）。整体排泄的Ｔ１／２ａ为５．２９ｈ，Ｔ１／２β为３９．３７ｈ；血液清除的Ｔ１／２ａ为４．２０ｈ，Ｔ１／２β为３４．６１ｈ。Ｆａｂ片段整体排泄的Ｔ１／２ａ为３．５１ｈ，Ｔ１／２β为２０．２２ｈ；血液清除的Ｔ１／２ａ为１．３９ｈ，Ｔ１／２β为２４．３９ｈ。提示：完整抗体适用于肿瘤导向治疗，显像诊断则以抗体片段为佳。     

Evaluation of biological response modifiers in the enhancement of tumor uptake of technetium-99m labeled macromolecules. A preliminary report.

Imaging tumors with radioactive monoclonal antibodies remains attractive but continues to be challenging. With the hypothesis that the use of biological response modifiers (BRMs) may augment the tumor uptake, technetium-99m(99mTc)-labeled tumor necrosis factor (TNF) and nuclear histone specific TNT-1-F(ab')2 were evaluated in tumor bearing mice given a single dose of interferon (IFN). Ukrain or pokeweed mitogen as BRMs. As early as 1.5 h post injection (p.i.) of the radioactive macromolecules, the absolute tumor uptake (% administered dose/g) of each agent was enhanced (e.g., TNF, control = 1.8 +/- 0.4, Ukrain = 3.2 +/- 0.5, P = 0.006) and tumor to muscle ratios were elevated (e.g., TNF, control a 4.1 +/- 2.2, interferon 8.3 +/- 2.7, P = 0.01). The absolute tumor uptake remained practically unchanged at 4 h p.i. Generally with BRMs, the blood clearance was rapid and tumor/blood ratios and tumor/muscle ratios were higher than in the control group, increasing to greater than 200% for IFN as a BRM. The early enhancement in tumor uptake of macromolecules, leading to excellent delineation of tumors by scintigraphy is highly encouraging and warrants further studies to explore the full potential of BRMs.     

抗人结肠癌单克隆抗体SC3A在荷瘤裸鼠体内的放射免疫定位研究

本文用~(131)I标记自制的抗人结肠癌单克隆抗体SC3A,进行荷人结肠癌裸鼠体内生物学分布和肿瘤的放射免疫显像研究。结果在注射~(131)I饲—SC3A后24～120h,肿瘤部位的放射性均显示出选择性浓聚,以72～120h的影像最为清晰;而注射~(131)I—鼠IgG则呈全身均匀性分布,无肿瘤部位选择性波聚影像。在72h,13种器官的T/NT均大于2,肿瘤LI为6.94,与扫描显像结果吻合。这些都表明SC3A在生物体内对结肠癌具有良好的选择性和导向作用,抗体可对其供临床体内进一步应用提供了依据。     

Kinetics of administered aggregated IgG in rats with passive Heymann's nephritis

The kinetics of radiolabeled heat-aggregated human IgG (AHIgG125I) were studied in rats with passive Heymann's nephritis (PHN) induced 72 hr previously with decomplemented rabbit antiserum to rat FX1A. Control rats were injected with decomplemented normal rabbit serum (NRS). Following administration of AHIgG125I (40 mg per 100 g of body wt) control and FX1A animals were sacrificed in groups of five each at 2, 4, 8, 16, and 24 hr and kidney, liver, spleen, lung, plasma, and blood cells obtained. 131I-Labeled human serum albumin (HSA131I) was administered prior to sacrifice as a plasma marker. In FX1A rats the following observations were made in comparison with control rats: (1) A decrease in the concentration of AHIgG125I in glomeruli was observed at 2, 4, and 8 hr after administration; (2) a significant increase in clearance reflected by a decrease in the concentration of plasma trichloroacetic acid (TCA)-precipitable radioactivity, and AHIgG125I (greater than 7 S) was present; (3) a significant increase in non-TCA-precipitable radioactivity in plasma and blood cells at most time periods; and (4) decreased concentrations of AHIgG125I in liver and spleen but not lung. The specificity of these observations was supported in separate experiments by the lack of any difference in the plasma levels of TCA-precipitable radioactivity after administration of radiolabeled albumin to FX1A and control rats. Studies in FX1A and control rats revealed no differences in body weight, kidney weight, hematocrit, blood volume, urine output, glomerular filtration rate, renal blood flow, or renal vascular resistance. A slight increase in urinary rat albumin excretion was observed in FX1A rats. The lower values of AHIgG125I observed in plasma, liver, and spleen associated with increased levels of non-TCA-precipitable radioactivity in plasma and blood cells suggest enhanced catabolism of AHIgG125I in FX1A rats, leading to decreased localization within the mesangium.     

Radioimmunolocation of a heterotransplanted human choriocarcinoma (BeWo) using monoclonal anti-SSEA-1: pharmacokinetics

Stage-Specific Embryonic Antigen-1 (SSEA-1), originally discovered on mouse teratocarcinomas, has since been found on some human non-seminomatous germ-cell tumors and adenocarcinomas, as well as on some adult mouse and human tissues. A monoclonal antibody to this antigen (anti-SSEA-1; IgM, kappa) was used for radioimmunolocation. Nude mice bearing the human choriocarcinoma BeWo, which is SSEA-1 positive, were injected using a mixture of [131I]anti-SSEA-1 and [125I]MOPC 104E, an unselected myeloma protein of the same heavy-chain isotype. Animals were sacrificed at 24 hour intervals; the radioactive deposition due to both antibodies was determined for both tumors and normal organs. Accumulation of anti-SSEA-1 in the tumor was consistantly rapid and specific, while little accumulation of the unselected myeloma protein occurred. At five days after injection, an average of 3% of the initial dose of specific antibody was retained per gram of tumor; the tumor/blood ratio was 11, tumor/muscle was 80. Gamma-camera imaging allowed ready location of the tumors. Tumors could also be imaged using F(ab')2 antibody fragments.     

Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning.

To determine whether tumors containing carcinoembryonic antigen could be detected by administration of a radiolabeled, affinity-purified, goat lgG having 70 per cent immunoreactivity against carcinoembryonic antigen, 18 patients with a history of cancer of diverse histopathology received an average total dose of 1.0 mCi of 131l-labeled lgG. Total-body photoscans were performed with a gamma scintillation camera at various intervals after administration of the radioactive antibody. Ordinary photoscans proved difficult to interpret because of blood-pool background radioactivity, thus necessitating the computer subtraction of radioactive blood-pool agents from the antibody's 131l activity. Tumor location could be demonstrated at 48 hours after injection in almost all cases studied. The scans were negative in patients without demonstrable tumors or with tumors apparently devoid of carcinoembryonic antigen. Circulating antigen levels of up to 350 ng per milliliter did not prevent successful tumor imaging after injection of the radioantibody.     

I131 in blood samples: management in the laboratory

OBJECTIVES: Patients treated by (131)I may require blood sampling in the days following its administration. We investigated the safety of such samples in terms of radioactivity and the possible disturbance of the analyses by these "131I-spiked" samples. METHOD: 1) The radioactivity of blood samples from 131I-treated patients was measured (dose rate, surface activity, total activity) ; 2) The risk for the personnel was subsequently evaluated and ; 3) The interference of this 131I-generated radioactivity on the results of routine automated and IRMA assays was investigated. RESULTS: 1) All RA measures but two were found below the European limits ; 2) Irradiation of personnel was negligible ; 3) The faint radioactivity did not disturb any analyses. CONCLUSION: These data demonstrate the safety that results from the negligible radioactivity in these blood samples.     

Luminal and basolateral uptake and degradation of insulin in the proximal tubules of the dog kidney.

In order to determine the major routes of insulin degradation in the body, insulin was labelled with a 'trapped' or 'residualizing' label: [125I]tyramine-cellobiose ([125I]TC) and injected intravenously in dogs. In contrast to conventional iodine-labelled insulin (131I-insulin), the [125I]TC-insulin allows measurements of total uptake in specific organs in vivo because the radioactive degradation products do not leave the cells. One h after the injection of trace doses, the amount of radioactivity recovered in the kidney from [125I]TC-insulin was nine times higher than when conventional [131I]insulin was used. In the blood, the amount of acid-precipitable radioactivity was the same for both labelled preparations, indicating similar clearance rates. A comparison of the uptake of insulin in filtering vs. non-filtering (ureter-occluded) kidneys indicated that the uptake of insulin is twice as high through the luminal than through the basolateral cell membrane; after 60 min, 8.9 +/- 0.8% of the injected [125I]TC-insulin dose remained in the filtering kidney and 3.2 +/- 0.2% of the dose was accumulated in the contralateral kidney, with occluded ureter but normal blood perfusion. In both filtering and non-filtering (ureter-occluded) kidneys, the subcellular distributions of [125I]TC-insulin were studied after various times by isopycnic sedimentation in sucrose gradients. No difference between peritubular and tubular uptake was discernible. The intracellular transport was rapid, leading to accumulation of radioactive label in dense lysosomes within 10 min.     

Radioimmunoimaging of human small cell lung carcinoma with I-131 tumor specific monoclonal antibody

In this study, an IgM monoclonal antibody (MAb600D11) directed against human small cell lung cancer (NCI-H69) was radiolabeled with iodine-131, and the biodistribution and image quality of the radiolabeled antibody was evaluated. Radiolabeling was achieved in a solid-phase system consisting of 1,3,4,6-tetrachloro-3a,6a-diphenylglycoluril. Labeling efficiencies and protein purification were accomplished using gel exclusion chromatography while radioimmunoreactivity was determined using a solid-phase radioimmunoassay procedure. The biodistribution of I-131-labeled MAbs was determined in Sprague-Dawley rats up to 7 days after injection. Highest organ concentrations were observed in liver (3.91 +/- 0.47 (SD) and 0.17 +/- 0.04 (SD) mean percent injected dose at 1-7 days after injections) and in thyroid (5.33 +/- 0.71 (SD) and 5.32 +/- 2.01 (SD) mean percent injected dose at 1-7 days after injection). Nude mice, bearing either a small cell lung tumor (NCI-H69) or a nonspecific tumor (adenocarcinoma), were injected with 400-800 microCi of I-131 labeled monoclonal antibody. Optimum tumor visualization was observed 2-4 days after injection with tumor concentrations as high as 10.4% of the initial injected dose. The results demonstrated that radioimmunoimaging of human small cell lung carcinoma was feasible with the tumor-specific IgM I-131-labeled MAb.     

Reduced red blood cell destruction by antibody fragments

Antibodies to blood group antigens can cause immune RBC destruction directly (extravascular destruction) or indirectly through subsequent complement activation (intravascular hemolysis). The Fc portion of the IgG antibody is responsible for the effector functions of immune RBC destruction. We hypothesized that sensitization of RBCs with blood group antigen-specific IgG antibodies lacking their Fc portion would escape from the recipient's immune system, allowing for a longer survival period of the RBCs in the circulation. Direct injection of mouse RBC-specific Ter-119 monoclonal antibody into mice resulted in a more severe anemia compared with that in mice injected with the Ter-119 F(ab')2 fragment. We found that mouse RBCs coated in vitro with the Ter-119 F(ab')2 fragment, when transfused into mice, survived longer in circulation compared with RBCs coated with whole Ter-119 IgG molecule. The data support the conclusion that antibodies can be rendered less pathogenic through removal of their Fc portion.