Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus

BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular carcinoma.Patients with hepatocellular carcinoma frequently experience portal vein embolism,which exacerbates the difficulty and complexity of treatment.125I particles,used in local radiotherapy,can directly act on tumor tissue and reduce damage to surrounding healthy tissue.Through retrospective analysis,this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment.AIM To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function.METHODS The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed.Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein(combination group),while 44 patients received treatment with transcatheter arterial chemoembolization alone(control group).The therapeutic effects on tumor lesions,primary liver cancer,and portal vein tumor embolisms were compared between the two groups.Changes in relevant laboratory indexes before and after treatment were evaluated.The t test was used to compare the measurement data between the two groups,and the χ^(2) test was used to compare the counting data between groups.RESULTS The tumor lesion response rate in the combination group(59.62%vs 38.64%)and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus(80.77%vs 59.09%)were significantly greater than those in the control group(χ^(2)=4.196,5.421;P=0.041,0.020).At 8 wk after surgery,the serum alpha-fetoprotein,portal vein main diameter,and platelet of the combined group were significantly lower than those of the control group,and the serum alanine aminotransferase,aspartate aminotransferase,and total bilirubin were significantly greater than those of the control group(t=3.891,3.291,2.330,3.729,3.582,4.126;P<0.05).The serum aspartate aminotransferase,alanine aminotransferase,and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery(P<0.05),and the peripheral blood platelet,alphafetoprotein,and main portal vein diameter were significantly less than those of the same group before surgery(P<0.05).CONCLUSION In patients with primary liver cancer and a thrombus in the portal vein,transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone.However,during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.

Preliminary application of 3D-printed coplanar template for iodine-125 seed implantation therapy in patients with advanced pancreatic cancer

AIM To evaluate a 3 D-printed coplanar template for iodine-125 seed implantation therapy in patients with pancreatic cancer. METHODS A retrospective analysis of our database was performed, and a total of 25 patients with pancreatic cancer who underwent iodine-125 seed implantation between January 2014 and November 2017 were analyzed. Of these, 12 implantations were assisted by a 3 D-printed coplanar template(group A), and 13 implantations performed freehand were selected as a control group(group B). A 3 D coplanar template was designed and printed according to a preoperative CT scan and treatment planning system. The iodine-125 seeds were then implanted using the template as a guide. Dosimetric verification was performed after implantation. Pre-and postoperative D90, V100, and V150 were calculated. The success rate of iodine-125 seed implantation, dosimetric parameters, and complications were analyzed and compared between the two groups.RESULTS Iodine-125 seed implantation was successfully performed in both groups. In group A, the median pre-and postoperative D90 values were 155.32 ± 8.05 Gy and 154.82 ± 16.43 Gy, respectively; the difference between these values was minimal and not statistically significant(P > 0.05). Postoperative V100 and V150 were 91.05% ± 4.06% and 64.54% ± 13.40%, respectively, which met the treatment requirement. A better dosimetric parameter was observed in group A than in group B, and the difference was statistically significant(V100: 91.05% ± 4.06% vs 72.91% ± 13.78%, P < 0.05). No major procedure-related complications were observed in either group. For group A, mild hemorrhage was observed in 1 patient with a peritoneal local hematoma due to mesenteric vein damage from the iodine-125 seed implantation needle. The hematoma resolved spontaneously without treatment. Postoperative blood amylase levels remained within the normal range for all patients.CONCLUSION A 3 D-printed coplanar template appears to be a safe and effective iodine-125 seed implantation guidance tool to improve implantation accuracy and optimize dosimetric distribution.

Stents combined with iodine-125 implantation to treat main portal vein tumor thrombus

AIM To evaluate the efficacy of main portal vein stents combined with iodine-125(^(125)Ⅰ) to treat main portal vein tumor thrombus.METHODS From January 1, 2010 to January 1, 2015, 111 patients were diagnosed with liver cancer combined with main portal vein tumor thrombus. They were non-randomly assigned to undergo treatment with transarterial chemoembolization(TACE)/transarterial embolization(TAE) + portal vein stents combined with ^(125)Ⅰ implantation(Group A) and TACE/TAE + portal vein stents only(Group B). After the operation, scheduled follow-up was performed at 6, 12 and 24 mo. The recorded information included clinical manifestations, survival rate, and stent restenosis rate. Kaplan–Meier curves, log-rank test and Cox regression were used for data analyses. RESULTS From January 1, 2010 to January 1, 2015, 54 and 57 patients were allocated to Groups A and B, respectively. The survival rates at 6, 12 and 24 mo were 85.2%, 42.6% and 22.2% in Group A and 50.9%, 10.5% and 0% in Group B. The differences were significant [log rank P < 0.05, hazard ratio(HR): 0.37, 95%CI: 0.24-0.56]. The rates of stent restenosis were 18.5%, 55.6% and 83.3% in Group A and 43.9%, 82.5% and 96.5% in Group B. The differences were significant(log rank P < 0.05, HR: 0.42, 95%CI: 0.27-0.63). Cox regression identified that treatment was the only factor affecting survival rate in this study.CONCLUSION Main portal vein stents combined with ^(125)Ⅰ can significantly improve survival rate and reduce the rate of stent restenosis.

Radical treatment of stage Ⅳ pancreatic cancer by the combination of cryosurgery and iodine-125 seed implantation

AIM:To investigate the therapeutic effect of radical treatment and palliative treatment in stage Ⅳ pancreatic cancer patients.METHODS:81 patients were enrolled in the study.Radical treatment was performed on 51 patients,while 30 patients were put under palliative treatment.The procedural safety and interval survival for stage Ⅳ pancreatic cancer(IS-Ⅳ) was assessed by almost 2.5 years of follow-ups.The IS-Ⅳ of patients under the two kinds of treatment,and the effects of treatment timing and frequency on IS-Ⅳ,were compared.RESULTS:The IS-Ⅳ of patients who received radical treatment was significantly longer than those who received palliative treatment(P < 0.001).The IS-Ⅳ of patients who received delayed radical or palliative treatment was longer than those who received accordingly timely treatment(P = 0.0034 and 0.0415,respectively).Multiple treatments can play an important role in improving the IS-Ⅳ of patients who received radical treatment(P = 0.0389),but not for those who received palliative treatment(P = 0.99).CONCLUSION:The effect of radical treatment was significantly more obvious than that of palliative treatment,and multiple radical treatments may contribute more to patients than a single radical treatment.

Iodine-125 implantation with transjugular intrahepatic portosystemic shunt for main portal vein tumor thrombus

BACKGROUND Main portal vein tumor thrombus(MPVTT), which has a high incidence, is the major complication of terminal liver cancer. The occurrence of MPVTT is always a negative prognostic factor for patients with hepatocellular carcinoma(HCC).Therefore, attention should be paid to the treatment of MPVTT and its complications.AIM To evaluate the efficacy of transarterial chemoembolization/transarterial embolization(TACE/TAE)+^(125)I seeds implantation with transjugular intrahepatic portosystemic shunt(TIPS) in treating MPVTT and its complications.METHODS From January 2007 to March 2015, 85 consecutive patients with MPVTT were nonrandomly assigned to undergo treatment with TACE/TAE + TIPS and ^(125)I implantation(TIPS-^(125)I group) or TACE/TAE + TIPS only(TIPS only group) in Beijing Shijitan Hospital, and all clinical data were collected. During 24 mo follow-up, the incidence of overall survival, stent stenosis and symptom recurrence was analyzed to evaluate the efficacy of TIPS-^(125)I.RESULTS During 24 mo follow-up of all patients, we collected data at 6, 12 and 24 mo. The rates of survival were 80%, 45%, and 20%, respectively, in the TIPS-^(125)I group,whereas those in the TIPS only group were 64.4%, 24.4%, and 4.4%, respectively(P < 0.05). The rates of symptom recurrence were 7.5%, 22.5%, and 35%,respectively, in the TIPS-^(125)I group, whereas those in the TIPS only group were31.1%, 62.2%, and 82.2%(P < 0.05). The rates of stent restenosis were 12.5%,27.5%, and 42.5%, respectively, in the TIPS-^(125)I group, and 42.2%, 68.9%, and84.4%, respectively, in the TIPS only group(P < 0.05). TIPS-^(125)I was found to be significantly favorable in treating MPVTT and its complications in patients with HCC.CONCLUSION TACE/TAE+^(125)I combined with TIPS is effective in treating MPVTT and its complications, improving quality of life of patients and reducing mortality.

Iodine-125 interstitial brachytherapy for experimental liver cancer

Objective：To study the effect of iodine-125 interstitial brachytherapy on liver cancer. Methods： Animal model of human liver cancer was established by injecting SMMC-7721 cells cultivated in vitro subcutaneously into the flank of BALB/c nude mice. Nude mice with tumor of 5 mm in diameter were randomly divided into 2 groups （n = 10）. One iodine-125 seed of apparent activity 0.8 mCi was implanted into the center of tumor in treatment group, whereas an inactive seed was implanted in control group. The other 20 nude mice with tumor reaching 10 mm in diameter were also treated as above. The size of tumor was determined weekly after implantation, and pathological examination and blood routine were taken on the 28th day. Results： Tumor growth was obviously inhibited in treatment group of tumor of 5 mm in diameter, and there was statistically significant difference in tumor volume between treatment and control groups （P〈0.01）. Around iodine-125 seed, apparent necrosis of tumor was shown in treatment group, accompanied by karyopyknosis and reduced plasma in residual tumor cells microscopically. Tumor growth was not inhibited in either treatment or control group of tumor of 10 mm in diameter. There was no obvious adverse effect except for decreased white blood cells in treatment groups. Conclusion： There is certain effect of iodine-125 interstitial braehytherapy on liver cancer, which is associated with the size of tumor.

To explore the curative effect of CT-guided Iodine-125 radioactive seed implantation in the treatment of stage Ⅳprimary hepatocellular carcinoma

Objectives: To explore the clinical efficacy and survival of CT-guided Iodine-125 radioactive seed implantation in the treatment of stage Ⅳ primary hepatocellular carcinoma.Methods: A retrospective study of 62 patients with primary hepatocellular carcinoma in our hospital from January2017 to December 2018 [60 males, 2 females, age(52.76 ± 10.82) years old], All patients were implanted with Iodine-125 radioactive seeds under CT guidance, followed up regularly after operation to observe the clinical efficacy, including comparison of changes in cancer size before and after treatment, tumor marker AFP, and improvement in complications such as abdominal pain and ascites. Follow-up 3–36 months to assess patient survival.Results: Among the 62 patients, 3 months after Iodine-125 radioactive seed implantation, 5 cases(8.1%) had complete remission of cancer, 33 cases(53.2%) had partial remission, 12 cases(19.4%) had stable lesions, and 12 cases(19.4%) had disease progression. The effective rate was 61.3%. The tumor volume(31.44 ± 14.51 cm3) was significantly smaller than before(50.96 ± 30.13 cm3)(t=5.303, p < 0.05). The tumor marker AFP(69.28 ±50.99) ug/L of 3 months after implantation was significantly lower than that before treatment(90.63 ± 68.58)ug/L(t=3.702, P < 0.05). The average survival time of Iodine-125 seed implantation for stageⅣhepatocellular carcinoma is 11.47 ± 0.85 months, and the median survival time is 9 months. The survival time of the group with better pathological differentiation(grade Ⅰ+ⅡⅠ) was significantly better than that of the group with poor differentiation(grade Ⅲ+Ⅳ)(x2=6.869 p < 0.05). Among the 38 patients with different degrees of abdominal pain,22 patients improved better than before;15 of 28 patients with different degrees of ascites were better than before. All patients had no serious complications related to treatment.Conclusions: Iodine-125 radioactive seed implantation therapy can safely and effectively treat hepatocellular carcinoma, and relieve the clinical symptoms of abdominal pain and ascites.

Experimental study of triplex-forming oligonucleotide targeted to the initiator of S gene of HBV labeled with ^(125)I

This study is used to investigate the feasibility of employing the Iodogen method to label triplex-forming oligonucleotide (TFO) targeted to the initiator of the S gene of HBV with 125I. A 17-mer oligonucleotides sequence was synthesized and grafted at the 5′ terminal with a tyramine group. Radioiodination of the tyramine-TFO with 125I was then performed using the Iodogen method. After TFO was labeled with 125I using the Iodogen method, the label- ing rate, the radiochemical purity, stability and bioactivity were determined, respectively. The results show that the radiolabeling rate and the radiochemical purity were 93% and 99%, respectively; and the radiochemical purity is more than 90% in vitro at -20°C on the 5th day after labeling; and the rate of 125I-tyramine-TFO binding to HepG2.2.15 cells was (37.2 ± 1.4)% and statistically different from the rate of HepG2 (p < 0.5). Hence, it is concluded that the labeling of oligonucleotides conjugated with tyramine using the Iodogen method is successful and is characterized with a high labeling rate, high stability, and a low loss of bioactivity of the labeled agent.

Expression and radiolabeling of Cas9 protein

As a robust platform for genome editing,CRISPR/Cas9 is currently being explored for engineering biology or therapeutics,yet means for quantitative detection of Cas9 proteins remain to be fully realized.Here,we expressed Cas9 proteins and developed a novel detection method that traced Cas9 based on radiolabeled iodine.Through optimizing the reaction conditions of reaction time,temperature and cycles,we obtained ^(125)I-Cas9 of high labeling yield.The prepared ^(125)I-Cas9 was stable in various media and preserved excellent genome editing efficiency.Thus,our strategy provides a convenient and efficient tool for further tracing biological behaviors of Cas9 proteins in living systems.

Implanting iodine-125 seeds into rat dorsal root ganglion for neuropathic pain: neuronal microdamage without impacting hind limb motion

The use of iodine-125 （L251） in cancer treatment has been shown to relieve patients＇ pain. Consid- ering dorsal root ganglia are critical for neural transmission between the peripheral and central nervous systems, we assumed that 125I could be implanted into rat dorsal root ganglia to provide relief for neuropathic pain. 125I seeds with different radioactivity （0, 14.8, 29.6 MBq） were im- planted separately through L4-5 and L5-6 intervertebral foramen into the vicinity of the L5 dorsal root ganglion, von Frey hair results demonstrated the mechanical pain threshold was elevated after implanting 125I seeds from the high radioactivity group. Transmission electron microscopy revealed that nuclear membrane shrinkage, nucleolar margination, widespread mitochondrial swelling, partial vacuolization, lysosome increase, and partial endoplasmic reticulum dilation were visible at 1,440 hours in the low radioactivity group and at 336 hours in the high radio- activity group. Abundant nuclear membrane shrinkage, partial fuzzy nuclear membrane and endoplasmic reticulum necrosis were observed at 1,440 hours in the high radioactivity group. No significant difference in combined behavioral scores was detected between preoperation and postoperation in the low and high radioactivity groups. These results suggested that the mechan- ical pain threshold was elevated after implanting 125I seeds without influencing motor functions of the hind limb, although cell injury was present.

Study of the Positioning Influence in the Water Activity Measurement during Leak Test of Iodine-125 Seeds

In the prostate cancer treatment, brachytherapy with iodine-125 seeds has been used. lodine-125 seeds are sealed radioactive sources, made by a titanium capsule containing the radioisotope inside. In the final phase of the seeds production, it is necessary to ensure that there is no leakage of the radioactive material. A leakage test is performed, immersing the seeds in water during 24 h and measuring the resulting activity in the water. This measurement is made in a sodium iodide detector. The immersion water is transferred to a plastic tube with a cap. The tube is placed by an automated positioning system, in the detector chamber. This study aims to determine the best positioning of the tube for the detection. It is also important to determine the influence of the positioning variation intrinsic of the automated positioning system during the iodine-125 seeds production. The results obtained will be used as a reference to adjust the equipment and process control system, in the production of the iodine-125 seeds.

Synthesis and radioiodinated labeling of p-iodophenylpentadecanoic acid

A new method for tile preparation of p-iodophenyl pentadecanoic acid (IPPA)has been developed. The synthesis are described, and physical properties of IPPA are characterized by IR, 1HNMR, elementary analysis and MS. 125I-IPPA can be easily prepared bytwo methods: direct labeling and solid-phase iodo-exchange labeling, and the yields of labelingare 80% and 65%, respectively. The radiochcnrical purities are higher than 98% after beingextracted with chloroform and he-cane.

Automation System for Quality Control in Manufacture of Iodine-125 Sealed Sources Used in Brachytherapy

The objective of this work is to develop an automation system for quality control （QC） in the production of Iodine-125 sealed sources, after undergoing the process of laser beam welding （LBW）. These sources, also known as Iodine-125 seeds are used, successfully, in the treatment of cancer by brachytherapy, with low-dose rates. Each small seed is composed of a welded titanium capsule with 0.8 mm diameter and 4.5 mm in length, containing Iodine-125 adsorbed on an internal silver wire. The seeds are implanted in the human prostate to irradiate the tumor and treat the cancerous cells. The technology to automate the quality control system in the manufacture of lodine-125 seeds consists in developing and associate mechanical parts, electronic components and pneumatic circuits to control machines and processes. The automation technology for Iodine-125 seed production developed in this work employs programmable logic controller （PLC）, step motors, drivers of control, electrical-electronic interfaces, photoelectric sensors, interfaces of communication and software development. Industrial automation plays an important role in the production of Iodine-125 seeds, with higher productivity and high standard of quality, facilitating the implementation and operation of processes with good manufacturing practices （GMP）. Nowadays, the Radiation Technology Centre at IPEN-CNEN/SP imports and distributes 36,000 lodine-125 seeds per year for clinics and hospitals in the whole country. However, the Brazilian potential market is of 8,000 lodine-125 seeds per month. Therefore, the local production of these radioactive seeds has become a priority for the Institute, aiming to reduce the price and increase the supply to the population in Brazil.

^(125)I-RGD-4CY肿瘤α_vβ_3受体显像的实验研究

目的 探讨放射性核素标记小分子环形多肽RGD 4CY实现肿瘤αvβ3 受体显像的可行性。方法 采用Iodogen法标记、SEP PAKC18柱分离纯化制备12 5I RGD 4CY。测定12 5I RGD 4CY在正常小鼠与荷人QBC93 9胆管癌裸鼠体内的放射性分布 ,计算肿瘤(T)与非肿瘤组织 (TN)放射性比值。进行12 5I RGD 4CY荷瘤动物全身放射自显影。结果 正常小鼠血液放射性清除和肝脏放射性下降迅速 ,肠道无明显增加 ,主要通过肾脏排泄 ,肌肉和肺的放射性 12 0min时分别仅为肝脏的 3 2 %与 44 % (P <0 0 5 )。荷瘤裸鼠各时相肿瘤的放射性均高于肌肉、肠道与肺 (P <0 0 5 ) ,2 40min时T/NT值分别为 2 6.0、8 7与 2 6.0。放射自显影示肿瘤放射性浓聚影最强 ,肺、颈部及其它软组织呈低水平分布。结论 放射性标记RGD 4CY可望成为一有效的肿瘤αvβ3

抗人CD40 mAb 5H6的^125I标记及其与卵巢癌细胞株HO8910体外结合的生物学特性

目的:研究抗人CD40单克隆抗体(mAb)5H6的125I标记及与卵巢癌细胞株HO8910体外结合的生物学特性。方法:氯氨-T法125I标记mAb5H6(125I-5H6),纸层析法测定125I-5H6的标记率和放射化学纯度,三氯醋酸沉淀法分析125I-5H6体外稳定性,细胞结合饱和实验进行Scatchard分析,lindmo法及其改良方法计算125I-5H6的免疫活性分数,细胞结合实验分析125I-5H6同HO8910细胞的内化和滞留。结果:(1)mAb5H6的125I标记率为(85.4±5.2)%,放射化学纯度为(99.2±0.5)%。(2)125I-5H6存放于4℃磷酸缓冲液中7d后其放射化学纯度为(80.3±4.7)%,在37℃血浆中存放24h后其放射化学纯度为(95.3±0.8)%。(3)125I-5H6与HO8910细胞亲和力Kd=(0.711±0.06)nmol/L,最大结合位点数(Bmax)=(2.17±0.08)×105个/细胞。(4)125I-5H6免疫活性分数达(38.6±5.4)%。(5)4℃2h125I-5H6同HO8910细胞滞留率为(89.8±6.0)%,37℃2h125I-5H6同HO8910细胞内化率达(54.9±2.6)%。结论:氯氨-T法进行125I-5H6标记具有良好的标记率和放射化学纯度,以及良好的体外稳定性和较高的免疫活性分数,且125I-5H6与HO8910细胞具有很高的亲和力,可用于动物体内实验。

^(125)I标记免疫球蛋白重链V1家族框架区反义寡核苷酸

用DNA合成仪将含酪胺的单体连接在18聚体寡核苷酸的5′端,并用氯胺-T法进行125I标记。该标记方法的标记率为80.7%,标记物放化纯度为98.7%,体外放置24h放化纯度仍高于90%。聚丙烯酰胺凝胶电泳(PAGE)显示各时间点的条带与未保温的对照组平行,均未见异常条带。

高纯度^(125)I-蛇毒神经生长因子的制备

介绍了１２５Ｉ－蛇毒神经生长因子（ＮＧＦ）的制备及鉴定。标记前纯品在ＷａｔｅｒｓＳＰ磺酸型阳离子交换高效液相（ＨＰＩＥＣ）中表现为单一峰，但１２５Ｉ标记后Ｓｅｐｈａｃｒｙ１Ｓ－２００ＨＲ凝胶标记蛋白部分的ＨＰＩＥＣ谱，除１２５Ｉ－蛇毒ＮＧＦ外，出现了分子量较大、与凝胶柱不结合的未知组分，提示可能发生聚合和表面电荷变化。结合蛇毒ＮＧＦ性质选用Ｓｅｐｈａｒｏｓｅ－ＳＰ阳离子交换柱去除上述未知组分。放化纯度和生物鉴定证明：两步纯化标记产物得到了放化纯度为９７％、有生物活性的１２５Ｉ－蛇毒ＮＧＦ。提示根据多肽特点选择纯化和鉴定方法是制备高纯度有活性标记多肽的重要环节。

NCI-H446细胞的^(125)Ⅰ-[Tyr^3]octreotide受体分析

目的 :探讨小细胞肺癌与 [Tyr3 ]octreotide (TOC)的亲和力。方法 :用氯胺T方法标记的12 5I-TOC作为配基 ,检测小细胞肺癌细胞株NCl-H4 4 6与其结合的受体位点数及亲和常数。结果 :氯胺T法标记的12 5I-TOC经SephadexG - 10纯化后放化纯大于 95 % ;受体分析显示NCI-H4 4 6表达的生长抑素受体多 (Bmax =1 17× 10 5受体位点 /细胞 ) ,与12 5I-TOC亲和力强 (Kd =0 5 8nM)。结论 :TOC的标记物可用于小细胞肺癌肿瘤的受体显像及放射治疗。

BMIPP的合成与^(125)I标记

报道了由ω溴十一烷酸制备β甲基对碘苯代十五烷酸(BMIPP)的合成方法。终产物经红外、核磁共振、元素分析和质谱等方法确证。同时报道了BMIPP的125I标记方法,经TLC检测,标记率和放化纯度分别大于80%和98%。

侧链脂肪酸 BMIPP 的 ^(125)I 标记和动物体内分布

在乙醇和水的混合溶液中，通过新生态Ｃｕ（Ｉ）催化碘同位素交换反应制得１２５Ｉ－ＢＭＩＰＰ，经乙醚提取纯化后，其放射化学纯度＞９５％，制备过程中总放射性得率＞４０％。小白鼠体内分布显示２％左右的注射剂量存在于心肌组织，且长时间保持稳定。