Biological distribution of I-labeled anti-nucleus antigen monoclonal antibody chTNT in patients with pulmonary metastases from differentiated thyroid carcinoma

This work is to study the in vivo biological distribution of ¹³¹I-labeled mouse/human chimeric monoclonal antibody (¹³¹I-chTNT) in patients with pulmonary metastases from differentiated thyroid carcinoma. Ten patients with differentiated thyroid carcinoma were injected intravenously with a single dose of ¹³¹I-chTNT (5 MBq·kg⁻¹ body weight). Radioactivity of blood and urine samples was measured at different time points. The in vivo stability and the metabolic status of ¹³¹I-chTNT were detected with supersaturated trichloroacetic acid. Continuous imaging was performed to outline the region of interest (ROI) and estimate the intake level on the whole body, major organs and tumor lesions at different time points. The serum time-radioactivity curve of ¹³¹I-chTNT accorded with the two-compartment model after a single intravenous injection: T_1/2(h)=65.28±14.83, AUC_0-t(MBq-h-mL⁻¹)=8.93±1.32, AUC_0-∞(MBq·h·mL⁻¹)=10.58±2.19, and CL(mL·min⁻¹·kg⁻¹)=1635±359. The time-radioactivity percentage curve of ¹³¹I-chTNT urine excretion accorded with the one-compartment model after a single intravenous injection: T_1/2(h)=99±10, and accumulative (31±9) % radioactivity of the injected dose was excreted in urine in one week. The percentages of serum ¹³¹I-chTNT in radioactive components at 24, 48 and 72 h were over 95% and it was still (88±7) % at 168 h. As for chemical composition of radioactive substances in urine, radioactivity in urine samples originated from free ¹³¹I by 100%. Radioactivity of ¹³¹I-chTNT after intravenous administration was mainly concentrated in the lung and liver, least in the brain. Radioactivity of tumor tissues reached the maximum at 24 h and the tumor/normal tissue (T/N) ratio reached the maximum (1.28-3.83) during 3-7 d. The characteristics of in vivo biological distribution of ¹³¹I-chTNT in patients with pulmonary metastases from differentiated thyroid carcinoma are favorable for its therapeutic application for the metastasis tumors.     

Dosimetry of chimeric TNT in lung tumor patients

The purpose of this study was to assess the absorbed dose of tumor and main critical organs in 131I labeled chimeric tumor necrotic treatment (chTNT). In 9 patients, a single intravenous dose of (29.6±3.7) MBq/kg was administered. Blood samples were drawn at different time intervals, and urine was collected for up to one week. Tissue distribution of 131I -chTNT was followed for up to one week by gamma camera imaging. Absorbed doses to the whole body and to normal organs were computed according to the MIRD scheme using Mirdose-3 software. S-factors for lung tumors were estimated by comparison with lungs of similar mass and position in the body. It was found that mean serum disappearance half time values for 131I-chTNT were (4.93±9.36) h and (61.7±21.2) h for α, β respectively,while that for whole body was(99±10) h. Mean urine biological clearance half time value was (90±10) h. The absorbed dose to tumor was (8.28±2.65) Gy, and the tumor-to-nontumor dose ratio was 3.95±1.55. And the mean effective dose to patients was (1.02±0.29) mSv/MBq.     

131I-chTNT-mediated radioimmunotherapy for non-uptaking 131I pulmonary metastases from differentiated thyroid carcinoma

In this paper, the safety and efficacy of 131I-labeled mouse/human chimeric monoclonal antibody （131I-chTNT）-mediated radioimmunotherapy are evaluated because the patients have non-uptaking 131I pulmonary metastases from differentiated thyroid carcinoma （DTC）. The 16 patients were injected intravenously by 29.6±3.7 MBq＇kg 1 using 131I-chTNT. The chest computer tomography was performed before treatment, as well as 28 and 70 days after treatment. Responses and safety were assessed during the treatment. The results show that the 131I-chTNT infusion was well tolerated with the 12.5% complete response, 18.8% partial response, 25.0% progressive disease, and the 43.8% stable disease, indicating that most treatment-related adverse effects are mild transient and reversible. The 131I-chTNT is promising for patients with non-uptaking the 131I pulmonary metastases from DTC.     

甲癌患者131I治疗出院标准及时间研究进展

¹³¹I治疗是分化型甲状腺癌患者术后安全、有效、重要的辅助治疗方式,同时有可能产生辐射危害。为了减少其辐射危害,甲状腺癌患者行大剂量¹³¹I治疗后需住院隔离治疗,其体内放射性活度、周围当量剂量率的高低等因素决定了患者需住院隔离时间的长短。本文介绍甲状腺癌患者¹³¹I治疗后出院标准、体内活度估算、辐射剂量的监测、住院隔离时间以及其预测因素等研究进展,为临床工作中实施规范、合理的出院标准以及进一步开展相关研究提供参考。     

Changes in percentage of lymphocyte subsets after ^131I treatment in patients with differentiated thyroid cancer

To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic ^131I administration, the percentage of lymphocyte subsets were serially analyzed before and after ^131I treatment. In patients who received 1850 MBq of ^131I for ablation of thyroid remnants, only tor NK cells and B cells showed a significant reduction. In patients received 3700 MBq of ^131I for treatment of local lymph node metastases, NK cells, B cells and CD4＋ were found decreased. In patients received 7400 MBq of ^131I for treatment of distant metastases, NK cells, B cells and CD4＋ and CD8＋ were all affected. However, there is no significant reduction compared to the baseline in the percentage of all lymphocyte subsets three months after ^131I treatment. The results show that the sensitivity of lymphocytes to ^131I internal radiation depends upon lymphocyte phenotype and ^131I activity. The immunosuppression effects are temporary and reversible.     

Tumor angiogenesis imaging agent:biodistribution of 131I-YG5 and 131I-Boc-YG5

The cyclic peptide YG5 and the t-butyioxycarbonyl(Boc)-modified analog(Boc-YG5)were labeled with radioiodine.The radiochemical purity of 131I-YG5 or 131I-Boc-YG5 was almost 100% after purification by RP-HPLC.Biodistribution in BALB/C nude mice bearing MCF-7 tumor was measured.After t-butyloxycarbonyl(Boc)-modification,the 131I-Boc-YG5 was quite resistant to deiodination in vivo,resulting in negligible radioactivity accumulation in thyroid.The radiotracer clearance in tumor became faster,the absolute tumor uptake decreased for131I-Boc-YG5,but the tumor-to-tissue uptake ratios increased.The uptake ratios of tumor to muscle,blood,heart,and lung at 1 h post injection reached 4.73,1.70,4.09 and 1.70,respectively.It is demonstrated that Boc-group is an effective prosthetic one to prevent deiodination in vivo and improve tumor imaging for radioiodinated NGR.     

Measurement of 153Sm-EDTMP bone uptake by whole-body scintigraphy and its application to individualized treatment dosimetry of bone metastasis

1 INTRODUCTIONSamarium-153 ethylenedialninetetramethylene phosphonic acid ("'Sin-EDTMP) iselective in the palation of painful bony metastases[1]. Pain relief is seen in 60%~90%of patients treated with "'Sin-EDTMP, and the onset Of pain relief generally beginswithin 1 week of administration. The critical organ in 153Sin-EDTMP therapy is thered bone marrow and myelotoalcity can be a significant side effect of the administrationof therapeutic activities of 153Sin-EDTMP[2]. There is…     

Human sodium/iodide symporter gene induced iodine uptake in human lung adenocarcinoma via baculovirus

To investigate human sodium/iodide symporter (hNIS) induced iodine uptake in human lung adeno- carcinoma via baculovirus, a recombinant baculovirus encoding hNIS gene was constructed under the control of CMV promoter (Bac-CMV-hNIS). In vitro, baculovirus infected A549 cells accumulated about 27 times more 125I than that of noninfected cells. The 125I uptake was maximal after 30-min incubation of the cells, and efflux of the radioactivity was rapid, with 50% lost during the first 2 min after 125I-containing medium had been replaced by nonradioactive medium. Competition experiments in the presence of sodium perchlorate revealed a dose-dependent decrease of 125I uptake. Bac-CMV-hNIS infected tumor cells were selectively killed by exposure to 131I, as revealed by clonogenic assays. In nude mice, Bac-CMV-hNIS infected A549 cells accumulated more 131I than that of the control monitored by 1-h scintigraphy after 131I administration. The transduction of hNIS gene through baculovirus is sufficient to induce iodine transporting in A549 cells in vitro and in vivo, outlining the potential of this novel tumor gene imaging approach. But a rapid efflux of radioactivity from the tumor was shown in vivo and the in vivo therapy test showed no sign of effect.     

Synthesis, radiolabeling and animal studies of [131I]MPPI: A 5-HT1A imaging agent

The synthesis and biological evaluation of serotonin (5-HT1A) imaging agent [131I]-4-iodo-N-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-N-pridin-2-yl-benzamide ([131I]MPPI) are reported. The chemical structure of aimed compound and intermediates were confirmed by IR, 1HNMR, and MS. Radiochemical purity was above 99% determined by TLC. Biodistribution of [131I]MPPI in rats displayed high uptake in hippocampus and low uptake in cerebellum. The ratio of the uptake of [131I]MPPI in hippocampus to that in cerebellum was 2.90 at 30 min post injection. The radioactivity in thyroid was 0.069 and 0.128% ID/g organ at 5 min and 120 min,respectively, and it was increased with time, which suggests that in vivo deiodination may be the major route of metabolism. Ex vivo autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when pretreated with 8-OH-DPAT, a selective 5HT1A agonist, compared with control. These findings strongly suggested that 131I-MPPI could be used as an in vivo marker for studies of pharmacology of the 5-HT1A receptor system in animals.     

分化型甲状腺癌患者行131I治疗辐射防护的知信行现状调查

为了解分化型甲状腺癌患者¹³¹I治疗辐射防护知信行现状及其相关影响因素,我们采用自行设计的辐射防护知信行问卷对某三甲医院核医学科2018年3—6月期间行¹³¹I治疗的330名甲状腺癌患者进行现场调查。结果提示,分化型甲状腺癌患者¹³¹I治疗辐射防护知识、态度、行为百分制平均得分分别为(58±17.88)分、(90.28±7.48)分、(72.13±7.83)分,三者两两正相关,学历是影响患者辐射防护知识水平的主要因素。甲状腺癌患者¹³¹I治疗辐射防护态度积极,但防护知识水平和行为不足,应注重出院后的防护措施指导,并重点关注低学历患者。     

^125I—抗Tg—McAb与甲状腺癌细胞结合的体外实验研究

选用自制的１８Ａ１和１８Ａ１１两株ＭｃＡｂ进行体外活细胞结合实验,定量观察＾１２５Ｉ标记的１８Ａ１和１８Ａ１１与正常甲状腺组织细胞及某些肿瘤细胞膜结合的反应性。实验结果显示,＾１２５Ｉ－抗Ｔｇ－ＭｃＡｂ与高分化甲癌细胞的结合率均〉３０％;与髓样癌结合率为８％－１２％;与正常甲状腺和甲状腺良性瘤细胞结合率〈１０％;其他细胞均〈４％。碘标记ＭｃＡｂ与正常甲状腺和甲状腺良性瘤细胞的结合率显著低于高分化甲     

分化型甲状腺癌患者的131I有效半衰期

通过测量分化型甲状腺癌患者在全甲状腺切除术后,接受131I治疗后对周围环境的辐射剂量率,采用单指数曲线拟合方法处理测量数据,计算出分化型甲状腺癌患者的131I平均有效半衰期为（14.6±6.5）h,该结果与国外文献报道均值接近,说明131I有效半衰期不存在人种差异性。对患者有效半衰期进行的统计学检验表明,患者有效半衰期与服药次数和年龄有负相关关系,与患者性别和服药量没有显著关系。     

131 Ⅰ治疗分化型甲状腺癌的辐射防护

分化型甲状腺癌(DTC)患者甲状腺全切或近全切术后常需要对患者行¹³¹I治疗,¹³¹I单次治疗剂量超过400 MBq时,需住院隔离。随着DTC患者的不断增加,¹³¹I应用越来越广泛,应用量越来越大,辐射防护问题受到人们的广泛关注。本文从病房环境防护、患者自身防护、医护人员防护及周围人群防护等几方面介绍了¹³¹I治疗后患者住院期间及出院后应该采取的防护措施及应注意的一些事项,可以更好地保护患者、医护人员及公众的健康。     

Synthesis, radiolabeling and animal studies of [~(131)I]MPPI: A 5-HTB_(1A) imaging agent

1 Introduction In the last two decades, considerable progress has been made in the understanding of the central nervous system (CNS) serotonin system. It is an important neurotransmission network that regulates various physiological functions and behavior, including anxi-ety and affective states.P[1-3]P The family of receptors activated by the neurotransmitter serotonin has been divided into at least seven classes (5-HTB1-7B), some of them further subdivided into different subtypesP[4, 5]P…     

甲癌患者131I治疗后手及颈部剂量当量率的监测与临床意义

为监测分化型甲癌(differentiated thyroid carcinoma,DTC)患者¹³¹I治疗后手及颈部近距离剂量当量率变化情况,指导患者如何进行最优化的辐射防护。以100例DTC患者按治疗次数分为两组,每组各50例,组1为首次行¹³¹I清甲治疗患者(服用¹³¹I剂量3 700～4 440 MBq),组2为再次行¹³¹I清灶治疗患者(服用¹³¹I剂量6 660～8 140 MBq),采用Inspector Alert γ射线检测仪分别对两组患者于¹³¹I治疗后出院时、出院后1周、2周、1个月及2个月进行双手及颈前部剂量当量率测量,测量距离包括颈前部、手掌部30 cm处及紧贴皮肤处。结果表明,(1)随着时间的延后,各监测时间点剂量当量率逐渐降低。患者出院后1个月距患者颈部、手掌部30 cm处剂量当量率、出院后2个月各监测部位剂量当量率均值均在天然本底范围内( 0.25 μSv/h) 。(2)¹³¹I治疗出院时,患者颈部剂量当量率均值均大于手掌部位,但出院后1周、2周及1个月,患者手掌部位剂量当量率均大于颈部。(3)出院后1个月内,一疗程患者颈部各时间点剂量当量率均值均大于二疗程(p＜ 0.05),二疗程患者紧贴手部各时间点剂量当量率均值明显大于一疗程(p＜ 0.05)。¹³¹I治疗患者刚出院时,各监测部位剂量当量率均较高(＞20 μSv/h),建议患者出院后1周内避免与他人亲密接触,2周内避免长时间超亲密接触,避免与特殊人群(如婴幼儿、孕妇等)零距离接触(如拥抱、亲吻等),出院后1个月距离患者≥30 cm的社交活动和出院后2个月的社交活动可完全不受限制。患者手部容易被污染导致剂量当量率较高,尤其是二疗程患者,应做好辐射防护隔离措施。     

~(125)I-rAncrod在大鼠体内的组织分布与代谢

为研究125I-rAncrod(1.59μg·kg-1)在Wistar大鼠器官和组织分布以及粪尿和胆汁的代谢情况,采用放射性125I标记重组安克洛酶(125I-rAncrod)结合分子排阻色谱法(size exclusion chromatography,SEC)及γ-计数法测定不同时间组织及体液样品中125I-rAncrod的含量。结果显示,放射性药物浓度主要累积在甲状腺和胃肠道内,肝肾次之,而脑、脊髓、脂肪、肌肉中药物浓度一直处于较低的水平。Wistar大鼠尾静脉注射125I-rAncrod后,SEC色谱图显示到48h粪尿和胆汁中均检测不到原形药物。结果表明,大鼠尾静脉注射125I-rAncrod后在全身各器官和组织分布广泛,代谢较完全。     

分化型甲状腺癌患者术后碘-131治疗前甲状腺功能减退对肝功能的影响

为探讨分化型甲状腺癌患者术后¹³¹I治疗前甲状腺功能减退对肝功能的影响，本研究回顾性分析经本院内分泌乳腺外科行甲状腺癌根治术后行¹³¹I治疗的258例分化型甲状腺癌患者，分别对术前与术后¹³¹I治疗前的肝功能指标及不同促甲状腺激素(thyroid stimulating hormone, TSH)分组下的相关参数进行比较，并进行肝功能指标与血清甲状腺功能检测指标相关性分析。结果表明，分化型甲状腺癌患者术后¹³¹I治疗前的各项肝功能指标均较术前升高，两组之间差异有统计学意义（P＜0.001）；不同TSH分组下，患者的年龄、血清白蛋白(albumin, Alb)、总胆红素(total bilirubin, TBil)、丙氨酸氨基转移酶(alanine transaminase, ALT)、天门冬氨酸氨基转移酶(aspartate transaminase, AST)、谷酰转移酶(lutamyl transferase, GGT)、空腹血糖在三组之间差异均无统计学意义（P＞0.05），仅直接胆红素(direct bilirubin, DBil)、碱性磷酸酶(alkaline phosphatase, ALP)在三组之间差异有统计学意义（P=0.022，0.016），且ALP随TSH的升高而升高；相关性分析结果显示，肝功能指标与血清甲状腺功能检测指标之间无显著相关性。分化型甲状腺癌患者术后¹³¹I治疗前甲状腺功能减退可导致肝功能轻度异常，但肝功能指标与血清甲状腺功能指标之间无明显线性相关，肝功能不会随着甲状腺功能减退程度的增加而进一步加重。     

Therapeutic safety evaluation of sodium glycididazole combined with ^131^I radiotherapy for differentiated thyroid carcinoma

To evaluate safety and therapeutic efficacy of sodium glycididazole (CMNa) combined with 131I radiotherapy for differentiated thyroid carcinoma (DTC),the 60 patients of DTC therapeutic protocols were selected and divided into 3 groups of the DTC 4.44 GBq 131I,DTC 3.70 GBq 131I,and combination of DTC 3.70 GBq 131I with CMNa,and the 20 patients of Graves’ Disease were selected as the control group.Peripheral blood was sampled at 131I pre-treatment of 1 day,and 131I post-treatment of 7,91,and 182 days,thus analyzing lymphocyte micronucleus scores and karyotyping profiles.Compared with the control group,the lymphocyte micronucleus and chromosome mutation rates in 131I treated DTC increased after post-treatment of 7 days,recovered after post-treatment of 91 days,and did not bounce after post-treatment of 182 days.The micronucleus and chromosome mutation rates in the combination of DTC 3.70 GBq 131I with CMNa showed less significant variation than other treated DTC groups.Our results demonstrate that micronucleus assay and karyotyping analysis are favorable to evaluate 131I radiotherapy for DTC.The combination of the CMNa with 131I radiotherapy was safe for DTC patients without affecting the long-term therapeutic outcomes.     

~(131)I标记新型小分子肽VP2

本文通过双功能偶联剂5-(三正丁基锡)-3-吡啶甲酸-N-琥珀酰亚胺酯(SPC)将131I标记到小分子融合多肽VP2上,研究了131I标记多肽VP2的体内外稳定性及在正常小鼠体内的代谢与分布。结果表明,该标记药物室温下放置48h后放化纯度仍可达97%,其在小鼠体内可通过胃肠道快速代谢,在甲状腺的摄取较低。用间接标记法得到的131I-SPC-VP2在体内外有良好的稳定性。     

血管抑素的131I标记及其对小鼠A549移植瘤治疗作用的观察

目的：从人血浆中分离血管抑素（ Angiostatin, AS），并用131I标记，观察131I- AS对荷A549移植瘤小鼠的治疗效果。方法：采用一步法从人血浆中分离AS，并用L-Lysine Sepharose 4B亲和层析柱作亲和层析纯化，将提纯的AS用Iodogen固相法进行131I标记，分析131I-AS 的标记率、比活度，并对其体外稳定性进行评价。32只荷A549肺癌移植瘤的裸鼠随机分为4组，腹腔注射131I- AS（含131I 11.1MBq，AS12.5mg/Kg）、131I（11.1MBq）、AS（12.5mg/Kg）和生理盐水0.3mL，1次/周，治疗四周，观察28天内肿瘤体积的变化。结果：131I- AS标记率为77.8~86.7 %，比活度为1.28~3.96MBq/ug。标记产物体外-20℃存放7天，放化纯度降至原来的72%。治疗28天后，131I- AS组、131I组、AS组和生理盐水组小鼠肿瘤的体积分别是（1956±98mm3）、（5284±123mm3）、（3948±115mm3）、（7350±153mm3）。结论： Iodogen法标记获得的131I-AG 标记率、比活度和稳定性较高。131I- AS能较强地抑制小鼠体内移植肿瘤的生长，其抑制作用优于单纯应用等浓度的AS及131I，131I- AS在治疗肿瘤中有潜在的应用前景。