Development of 153Sm-bleomycin as a possible therapeutic complex

<正>Due to interesting therapeutic properties of ~(153)Sm and antineoplastic antibiotic,bleomycin(BLM), ~(153)Sm-bleomycin(~(153)Sm-BLM) was developed as a possible therapeutic compound using ~(153)SmCl_3 and BLM.The ~(153)SmCl_3 was obtained by thermal neutron flux(5×10~(13)n·cm~(-2)·s~(-1))of an enriched ~(152)Sm_2O_3 sample,dissolved in acidic media.Under optimized conditions(room temperature,45 min,0.1 mg bleomycin for 740-3700 MBq ~(153)SmCl_3) a radiochemical purity over 98%was obtained shown by HPLC(Specific activity = 55 TBq/mM).The ~(153)SmCl_3 and ~(153)Sm-BLM were administered into wild-type rats up to 96 h followed by biodistribution.The SPECT imaging of labeled compound in wild-type rats was performed and significant image pattern was observed for a radiolabeled bleomycin compound.The ~(153)Sm-BLM is a potential therapeutic compound and our experiments on this compound have shown satisfactory quality,and stability suitable for future therapeutic studies.     

Biodistribution study of [^61Cu]pyruvaldehyde-bis （N-4-methylthiosemicarbazone） in normal rats as a PET tracer

[61Cu]-labeled pyruvaldehyde-bis (N-4-methylthiosemicarbazone) (61Cu-PTSM), a promising agent made for imaging blood perfusion, was produced via the natZn(p,x)61Cu nuclear reaction in a 30 MeV cyclotron, and separated by a two-step column chromatography method developed in our laboratory using a cation and an anion exchange resin. After 150μA irradiation for 76 min, about 6.006 Ci of 61Cu2 was obtained with a radiochemical separation yield of 95% and a radionuclidic purity of 99%. 61Cu-PTSM was prepared using an optimized method with in-house synthesized PTSM ligand for radiolabeling following quality control procedures using RTLC and HPLC. The tracer is mostly incorporated in heart, kidneys and brain compared to free copper cation as a control. These are in agreement with former reports. In conclusion, [61Cu]-PTSM was prepared at the radiopharmaceutical scales with high quality and is a potential PET tracer in the perfusion study of the heart, kidney, brain and tumors.     

Preparation, quality control and biodistribution of [^61Cu]-doxorubicin for PET imaging

This work was conducted for radiolabeling of an anticancer antibiotic, i.e. doxorubicin with 61Cu for pro-duction of possible tracer used in PET oncology. 61Cu was prepared with natural zinc target and 22 MeV150 mA pro-tons via natZn(p, xn)61Cu reaction with a yield of 123.2 MBq·μA-1·h-1. Optimization reactions were performed for pH, temperature and concentration. Biodistribution of the tracer was studied in normal and fibrosarcoma bearing mice. At the optimized conditions, ITLC showed that radiochemical purity was over 97% with a specific activity of 2.22×103MBq ·mmol-1·L-1. This was kept unchanged even with presence of human serum as well as room temperature for 5 h. Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated significant tumor uptake after 2 h. This tracer can be used in the detection of various tumors responding to doxorubicin chemotherapy using PET scan and/or determination of tumor therapy response to doxorubicin chemotherapy.     

Preparation and preliminary evaluation of [55Co](Ⅱ)vancomycin

Co-55 (t1/2=17.53 h) was produced by 150 μA irradiation of a natural nickel target using 15 MeV protons. It was separated from the irradiated target material by two ion exchange chromatography steps with a radiochemical yield of>95% and was used for the preparation of [55Co]vancomycin ([55Co]VAN). Optimization studies were per-formed using Co-57 due to its longer half-life. Cobalt-57 (t1/2=271.79 d) was produced by irradiation of a natural nickel target with 150 μA current of 22 MeV protons. The 57Co was separated from the irradiated target material using a no-carrier-added method with a radiochemical yield of>97%. Both products were controlled for radionuelide and chemical purity. The solutions of [55Co]VAN were prepared (radiochemical yield>80%) starting with 55Co acetate and vancomycin at room temperature after 30 min. A precise solid phrase extraction (SPE) method was developed using Si Sep-Pak in order to purify/reconstitute the final formulation for animal studies. [55Co]VAN showed a radiochemical purity of more than 99%. The resultant specific activity was about 1.15 TBq/mmol. It is proved that the tracer is stable in the final product and in presence of human serum at 37℃ up to 24 h. Biodistribution study of [55Co]VAN in normal rats was undertaken for up to 72 h.     

放射性标记生长抑素类似物在甲状腺癌诊治中的应用

在绝大多数分化型甲状腺癌不摄取放射性碘或对连续性放射性碘治疗不敏感的患者中,放射性标记生长抑素类似物的摄取明显,因而可以进行生长抑素受体显像和大剂量肽受体核素治疗.本文主要讨论90Y和177Lu标记的生长抑素类似物在甲状腺癌诊治中的应用,并讨论了前景较好的新型放射性标记生长抑素类似物.     

Preparation and preliminary evaluation of [^55Co]（II）vancomycin

Co-55 (t1/2=17.53 h) was produced by 150 μA irradiation of a natural nickel target using 15 MeV protons. It was separated from the irradiated target material by two ion exchange chromatography steps with a radiochemical yield of >95% and was used for the preparation of [55Co]vancomycin ([55Co]VAN). Optimization studies were per- formed using Co-57 due to its longer half-life. Cobalt-57 (t1/2=271.79 d) was produced by irradiation of a natural nickel target with 150 μA current of 22 MeV protons. The 57Co was ...     

Screening tumor-targeting bacteriophage particles by pre-clearing phage display

Phage display technique provides a powerful approach for the discovery of new tumor-specific peptides.However,the peptides isolated through this technique usually did not possess high tumor-specific property.A pre-clearing step was introduced to increase the efficiency of biopanning by removal of particles that could interact with ubiquitously expressed cellular receptors in the non-target organs.The randomized Ph.D-CX7C phage library (Phage III) was first pre-cleared in normal mice to reduce vasculatureor organ-targeting phages to get the pre-cleared phage library,and then the tumor-targeting bacteriophage particles (Phage I) were screened from pre-clearing phage library in S180 tumor-bearing mice.The biodistribution results of 99mTc-labeled phages in mice bearing S180 tumor show that the uptake of 99mTc-labeled Phage I in tumor is high but low in normal organs,and the tumor-to-liver and tumor-to-spleen ratios of 99mTc-labeled Phage I are higher than those of 99mTc-labeled Phage II (tumor-specific phages screened from the original CX7C library) and Phage III (unscreened phages from the original CX7C library).It indicates that the yield of tumor-targeting bacteriophage particles could be improved and the non-specific binding in organs becomes weak.Consequently,the pre-clearing phage display method could improve the yield of positive hits by reducing the non-target organ accumulation of bacteriophage particles.     

~（99m）Tc－植酸钠示踪法测定脾切除后网状内皮系统功能的变化

用９９ｍＴｃ－植酸钠示踪法测定Ｗｉｓｔａｒ大鼠脾切除后伴有或不伴有脓毒症情况下网状内皮系统（ＲＥＳ）的功能，同时观察了血浆纤维连接蛋白（ＰＦｎ）和透明质酸（ＨＡ）的变化。结果发现脾切除后，尤其合并感染时，血中清除半衰期延长，吞噬指数Ｋ值、肝脏吞噬功能降低，ＰＦｎ减少，ＨＡ浓度升高；这些均与ＲＥＳ功能受抑及脾切后感染的发生有密切关系。     

亲和素-生物素系统的153Sm标记及其生物学分布动力学的研究

选用＾１５３Ｓｍ对生物素进行放射性标记,然后利用亲和素和链霉亲和素与生物素的高亲合力特性,再对亲和素和链霉亲和素进行＾１５３Ｓｍ的标记,观察到大鼠和小鼠体内的血清除率和生物学分布,并与＾１５３ＳｍＣｌ３和＾１５３Ｓｍ－ＤＴＰＡ的生物学分布进行比较。结果表明,＾１５３Ｓｍ标记的亲和素血素除迅速,肝肾放射性摄取高;＾１５３Ｓｍ标记的链霉亲和素血清除缓慢,肝、脾、肾等脏器和血液中滞留量高;而＾１５３Ｓｍ     

Nanographene oxide labeling with 188Re

Nanographene oxide (NGO) is currently being explored for various biomedical applications. However, little information is known about its biological behaviors in vitro and in vivo. For further studying its pharmacokinetics and related biological behaviors in living systems, an effective and convenient tracing method is particularly demanded. In this work, NGO was labeled with radionuclide 188Re (188Re-NGO). To obtain high labeling yield and purity, a number of labeling conditions, including concentration of SnCl2 and ascorbic acid, reaction time and temperature, and pH were optimized, and stability of the 188Re-NGO in vitro and in vivo was evaluated. The results showed that NGO could be effectively labeled with high yield. The purified 188Re-NGO showed high stability in vitro and in vivo. A pretest of NGO biodistribution with single photon emission computed tomography showed that the 188Re-NGO was rapidly taken by organs such as lungs, liver, and spleen. The biodistribution of 188Re-NGO differs significantly from the free radionuclide, indicating that the labeling procedure is highly suitable for investigating its biological behavior in living systems.     

8192点分辨核能谱显示系统

本文描述用于“基于微型机的高分辨率核能谱分析系统”的具有8192显示点的高分辨核能谱显示系统。介绍其工作原理,主要功能,给出总体框图与实验结果。     

铼[188Re]标记人血清白蛋白的新方法研究

以含吡啶环的化合物[二(2-吡啶甲基)-氨基-乙酸(H2L)为双功能螯合剂,使用fac-[188Re(CO)3(H2O)3] 间接标记人血清白蛋白(IgG),为fac-[188Re(CO)3(H2O)3] 标记蛋白或单抗寻找新方法.fac-[188Re(CO)3(H2O)3] 标记条件研究表明,以活泼酯188Re(CO)3-L2H-TFPTFP,2,3,5,6-四氟酚)间接标记lgG时,标记率大于82%.在生理盐水和小牛血清中,48 h后产物的放化纯度均大于90%;以fac-[188Re(CO)3(H2O)3] 直接标记IgG作对比,标记率仅60%.在生理盐水和小牛血清中,48 h后产物的放化纯度＜60%.总的说来,使用fac-[188Re(CO)3(H2O)3] 间接标记生物分子时,具有对称结构的含吡啶环的化合物H2L是潜在的双功能螫合剂.     

经Avidin—Biotin系统^99mTc标记单抗及其在荷瘤裸鼠体内分布研究

采用Ａｖｉｄｉｎ－Ｂｉｔｉｎ系统进行了抗人黑色素瘤单抗Ｎｇ７３的＾９９ｍＴｃ标记、研究了标记条件，方法和标记抗体在荷裸鼠活体内的生物学分布１。结果表明，ｐＨ＝８和ＳｎＣｌ２适量时标记效果最好；两步法Ｂ的Ｔ／ＮＴ和ＩＤ％／ｇ值均明显优于两步法Ａ。经Ａｖｉｄｉｎ－Ｂｉｏｔｉｎ系统＾９９ｍＴｃ标记单抗可用于放射免疫显像。     

NPTC-11数字显示智能控制仪表研制

过程控制仪表准确与否,直接影响核电厂安伞运行,因此,对此类仪表的国产化更新改造,经验的积累十分必要。本文遵循核级仪表设计标准,充分考虑电站实际使用需求、技术冗余等因素,研制了NPTC-11数字显示智能控制仪表。经过近一年的核电站实用检验表明,该仪表符合研制目标,满足预期的研制要求。     

三羰基锝([99mTc(CO)3(OH2)3]+)标记 Morpholino寡核苷酸

采用三羰基锝药盒制备三羰基锝([99mTc(CO)3(OH2)3]+),并以DTPA作为双功能螯合剂,标记人工合成的Morpholino寡核苷酸.高效液相色谱(HPLC)证实,此方法三羰基锝产率大于90%,且产率稳定;Morpholino 寡核苷酸的标记率为(63±7)%,纯化后比活度为(9.62±1.26)GBq/μg;标记的Morpholino寡核苷酸在生理盐水及新鲜人血清中经过48 h仍保持其稳定性(＞90%),并保持与其互补链的杂交特性.总之,药盒法制备三羰基锝是一种简单而可靠的方法.Morpholino可以被三羰基锝成功标记并保持其生物活性.     

核电站安全参数显示系统的研究与设计

简要介绍了核电厂安全参数显示系统（ＳＰＤＳ）的设计特点和系统功能特点,包括设计准则、系统结构、多级显示、人因原则、自动诊断以及对ＳＰＤＳ的检验手段等。     

基于VME总线的触发硬件测试系统设计

介绍了VME手动机箱控制器与VME通道显示板的设计.在设计中充分利用FPGA的特点,因而该系统具有简单,可靠性高,以及灵活可变的特点.     

Peptides radiolabeled with Re-186/188 and Tc-99m as potential diagnostic and therapeutic agents

Small peptide-based compounds have attracted an enormous interest as carrier molecules to selectively deliver radionuclides to target tissues, sparing critical normal organs. When looking for ＂matched pairs＂ of radionuclides, suitable for radiolabeling of peptides for diagnosis and therapy, technetium and rhenium represent an almost ideal constellation. The important role of technetium-99m and Re-186/188 is based on the decay characteristics, suitable for tumor diagnosis and therapy. Tc-99m and Re-188 are readily available by either a ^99Mo/^99mTc or the ^188w/^188Re radionuclide generator system Furthermore, technetium and rhenium are chemically related and share structural as well as reactive similarities, which prompt an attractive ＂matched-pair＂ situation. This article shows an overview of ^99mTc- and ^186/188Re-radiolabeled peptides that have been tested for their potential use as imaging and therapeutic agents in oncological diseases.     

基于AD7888的嵌入式便携测量仪的设计与实现

传统的测试仪器只能对数据进行采集存储,并不能对获得的数据进行显示,文章介绍了一种以arm为控制核心的具有液晶显示屏的便携式测试系统,该系统能将采集到的数据实时地在界面上显示出来,系统采用S3C2440处理器和AD7888做为硬件平台,并在Linux操作系统上开发出了相应的应用程序,能够实现数据的采集存储、处理、波形显示等功能。为了功能上的完备性,外扩了USB接口。     

RS-485在核电站硼表系统就地显示中的设计与实现

介绍了核电站硼表系统中基于RS-485串口通讯的就地显示箱的研制,并重点对就地显示箱通讯协议、通讯内容和主要功能的约定进行了阐述.