Pharmacological studies of dopamine transporter imaging agent 125／131I－β－CIT

To prepare ^125/131I-β-CIT(2β-carbomethoxy-3β-(4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT),the labeling method from tributylstannyl precursor with peracetic acid has been reported in this article.The radiochemical purity(RCP) of the labeled compound was over 95% determined by HPLC and TLC.The stability,partition coefficients were also determined.The pharmacological studies of the imaging agent were performed in rats,mice,rabbits and normal monkey.The ligand showed preferable uptake in rats,mice,rabbits and normal monkey.The ligand showed preferable uptake in brain (1.9%ID/organ in rats and 4.5%ID/organ in mice at 5min).The ratios of striatum/cerebellum,hippocampus/cerebellum and cortex/cerebellum were 29.8,3.97and 4.75 at 6h in rats,and 8.52,2.99 and 3.06 at 6h in mice,respectively.In monkey brain imaging the ratios of striatum/frontal cortex(ST/FC)and striatum/occipital cortex(ST/OC) were 5.14 and 5.97 at 4h.respectively,All of above showed the high affinity of the ligand to DAT,The compound was primarily metabolized in liver because the hepatic uptake was much higher than other organs(75.4%ID/organ at 18h).The half-life of blood elimination was 5min.The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity,which evaluated the safety of the agent.All the results suggest that β-CIT can be used as a potential DAT imaging agent.     

Effect of ^188Re on chromosome aberration in human peripheral blood lymphyocytes

Human peripheral blood exposed with ^188ReO4^- at various radioac-tivities for 54h was examined to observe the chromosome and chromatin aberrations at metaphases in the mitosis of lymphocytes ,The findings indicate that there is an increasing tendency of the aberration yields of both types with incereasing ^188ReO4^- concentration and a dose dependency could be obtained .The aberration yield was best fitted by a quadratic model.Chromatin aberrations,aberration cells and chromosome fragments were fitted into a linear-regression model.     

A study on indirect radiolabeling of IgG with carrier free ~(188)Re

188Re labeled monoclonal antibodies are potential candidates for use in radioimmunotherapy. S-Bz-MAG3 as a bifunctional chelating agent was used for labeling of IgG with carrier free 188Re by pre-radiolabel-ing of the chelating approach. The conjugation conditions were optimized. The stability of 188Re-MAG3-IgG in vitro was high. The results may be useful to the studies of 188Re labeled MAbs for radioimmunotherapy.     

^188Re—labeled McAb 3H11 used as preventive for the peritoneal micrometasis of gastric cancer

In advancing gastric cancer, especially when the serous is invaded, the plantation of cancer cells in peritoneal is common and it affects patients' survival time severely. Based on successfully labeled McAb (monoclonal antibody) 3H11 with ~(188)Re, we investigated the effect of RIT (Radioimmuno-Therapy) with ~(188)Re-3H11 on preventing the peritoneal micrometastasis of gastric cancer cells in nude micc to increase the survival time. After 1×10~6 BGC-823 gastric cancer cells were injected into the peritoneal cavity of each mouse, 45BABL/C nude mice were divided into 9 groups. Each group received different doses of ~(188)Re-3H11 or ~(188)Re-IgG, or saline I.P.16 hours postoperation. The injected volume of each mouse was 1.0mL. The results showed that the survival time depended on the injected doses during 0 to 37 MBq. The survival time was 170±25.3d after 37MBq ~(188)Re-3H11 were treated. It was over 5 times more than that for the saline group and about 3 times more than that for 37 MBq ~(188)-Re IgG gro     

METABOLIC KINETICS OF BRAIN MUSCARINIC CHOLINERGIC RECEPTORS IN NORMAL AND HYPOTHYROID MICE

A technique for studying in vivo the production rate and turnover rate constant of mouse brain M-receptors was established. A single injection of 25 mg / kg of Benzilylcholine Mustard to living mice resulted in 90 % irreversible block of brain M-receptors. The time course of the receptor density was then monitored by 3H-QNB binding assay and the production rate and turnover rate constant were calculated from the time course curve with a computer program. It was found that in normal mice the turnover rate constant was about 0.035 h-1 (half-life was about 20 h) and the production rate was 30-42 fmol / (h ·mg protein). Parallel experiments revealed a significant slow down of the turnover of brain M-receptors in hypothyroid mice (turnover rate constant was 0.0257±0.0012 h-1 in hypothyroid vs. 0.0356±0.0021 h-1 in normal) while the production rate was not changed significantly. The results suggest that thyroid hormones have a regulatory action on the turnover of brain M-receptors and the elevation of brain M-receptor density together with slow down of the turnover of brain M- receptors is probably one of the important mechanisms relevant to the brain dysfunction in hypothyroidism.     

Investigation on oxidation states of rhenium in Re-HEDP

The oxidation states of rhenium in Re-HEDP (hydroxyethylidene diphosphonate) were measured by the methods of extraction and potentiometric titration. The oxidation state of rhenium in Re-HEDP was mostly +4 valence, and the Re(IV)-HEDP was oxidized to Re( V)-HEDP when it was titrated by 1, at pH 2.0. In the reduction system of Vc+Sn2+, ReO4- was only reduced by Sn2+, but Vc was oxidized earlier than Sn2+ when it was titrated by     

Study on technetium-99m labeling of graphene oxide nanosheets through click chemistry–~(99m)Tc labeling of graphene oxide nanosheets

Graphene oxide(GO)nanosheets possess several advantages,such as a large surface,outstanding biocompatibility,and straightforward chemical modification capability.They also have great potential as a drugcarrier.In this article,we radiolabeled GO nanosheets with99mTc,which satisfies the potential needs of microSPECT imaging probes in pre-clinical and clinical research.GO nanosheets were synthesized through the modified Hummers’method,then GO nanosheets with azide group covalently functionalized in two steps were conjugated to DOTA(1,4,7,10-tetraazacyclododecane-N,N,N,N-tetraacetic acid)and functionalized with an alkynyl group by means of click chemistry.Then through the addition and reduction of technetium-99m,the99mTc-DOTA-GO were attained.DOTA-conjugated GOs with lateral dimensions of 500–600 nm were synthesized.Both atomic force microscopy(AFM)and FT-IR were performed to characterize the GO-DOTA.Labeling efficiency of GO-DOTA with99mTc was90%and radiochemical purities were96%with purification.We successfully synthesized graphene oxide derivatives,DOTA-conjugated GOs,via Click Chemistry,and it was labeled with99mTc for SPECT imaging.High radiolabeling efficiency makes GO nanosheets suitable platforms for future molecular imaging research.     

The Influence of Iron on Ammonium Ion Generation from Nitrate Ion in Liquid Phase

Flue gas cleaning in discharge plasma process has been Studied intensively and we have tried to remove the NOx and S02 using the wet-type plasma reactor. In this system, NO is oxidized to NO2 and absorbed as NO3^-, and SO2 is absorbed as SO3^2- and oxidized in the liquid to SO4^2-. But the concentration of NO3^- was saturated and the absorption of NOx and SO2 was inhibited. Then, the reduction of NO3^- in the liquid is required. We examined the reductive reaction of NO3^- to NH4^ using discharge above the liquid surface then the pH value of the liquid was changed to alkaline slightly. When the Fe plate was used as a ground electrode in the liquid, NH4^ was generated. Then, the relation between the generation of NH4^ and Fe ions (Fe^2 and Fe^3 ) was studied. When Fe^2 was presented in the liquid, NH4^ was generated and Fe^2 was oxidized to Fe^3 . Fe^2 is required to generate NH4^ from NO3^-. When NH4^ was generated from NO3^-, both the calculated pH value from NH4^ concentration and the measured pH value indicated a similar value. From these results, the discharge above the liquid surface was effective to convert NO3^- to NH4^ and the reductive reaction leads to more absorption of NO3^-. These results showed that the wet-type plasma reactor is effective for NOx and SO2 removal system.     

Preparation of liposome-coated oligonucleotide labeled with 99mTc and its uptake in vascular smooth muscle cells

To explore the preparation method of liposome-coated 99mTc-labeled antisense oligonucleotide (ASON),targeteing the proliferating cell nuclear antigen (PCNA), and to explore the biological characteristics and the uptake kinetics of a radiolabeled probe in vascular smooth muscle cells, an 18-base single-stranded antisense oligonucleotide targeting PCNA mRNA and the complementary strand (sense oligonucleotide, SON) were synthesized. The ASON (SON) was labeled with 99mTc, by conjugating the bifunctional chelator (hydrazino nicotinamide, HYNIC), and purified through a gel filtration column of Sephadex G-25. The product was then encapsulated in cationic liposome (oligofectamineTM). The radiolabeling efficiency, radiochemical purity, stability of the liposome-coated 99mTc-HYNIC-ASON in a phosphate buffered solution (PBS), and fresh human serum and its uptake rate were studied. There was no significant difference between the 99mTc radiolabeling efficiencies of HYNIC-ASON and HYNIC-SON, which were 60.04% ± 1.92% and 59.60% ± 2.53%, respectively (P ＞ 0.05, n = 5). The radiochemical purity of the liposome-coated 99mTc-HYNIC-ASON was 94.70% ± 1.90% (n = 5). And after incubation with PBS and fresh human seAt 90 min after transfection, the uptake rate of the liposome-coated 99mTc-HYNIC-ASON reached its peak of 83.8% ±5.92% in vascular smooth muscle cells (VSMCs) and was much higher than that of the nonliposome-coated 99mTc-HYNIC-ASON, which was 11.16% ± 0.54% (P ＜ 0.01, n = 4). The labeling method of PCNA ASON (SON) conjugated by HYNIC has been proved successful. The liposome was able to enhance the ASON (SON) uptake in VSMCs,and could be widely used as a safe, convenient, effective gene transfer carrier.     

Synchrotron radiation X-ray fluorescence analysis of Fe,Zn and Cu in mice brain associated with Parkinson’s disease

The contents and distributions of metal elements in the brain are closely related to neurodegenerative diseases.In this study, we examined Fe, Cu and Zn contents in the brain section associated with Parkinson‘s disease(PD)using synchrotron radiation X-ray fluorescence(SRXRF). PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-terahydropyridine(MPTP) was used for the elemental analysis(e.g., Fe, Cu and Zn) in the substantia nigra pars compacta(SNpc) region of mice brain tissue samples. We found that mice in the MPTP group had higher contents of Fe, Cu and Zn in the SNpc than the control group. After treating the PD mice with rapamycin, the contents of Fe, Cu and Zn were reduced, the dopamine neurons and motor function were rescued correspondingly. The results prompted that the SRXRF provided an ideal method for tracing and analyzing the metal elements in the brain section to assess the pathological changes of PD model and the therapeutic effect of drugs.     

186Re对抗人脑胶质瘤单克隆抗体的标记条件及其体外稳定性研究

用＾１８６Ｒｅ对抗人脑胶质瘤单克隆抗体（ＭＡｂ ＳＺ３９）进行了标记。研究了影响标记率的多种因素：如不同转移螯合剂、不同反应时间、ｐＨ及不同的ＳＺ３９还原剂等,最终找到了最佳反应条件,选用低ｐＨ的葡萄糖酸钠－盐酸缓冲溶液,标记率高达９６．２％。通过测量相同反应条件下标记率,发现＾１８６Ｒｅ比活度太阳明显降低标记率。标记物进行了高效液相分离与纯化,并对纯化物作了体个稳定性测试,测定了不同条件下放化纯     

ReO4^—在葡萄糖酸钠介质中还原后的氧化态分布研究

用电位滴定法和萃取法研究了 Ｒｅ Ｏ４－ 在葡萄糖酸钠介质中还原后铼的氧化态分布。实验结果表明,铼氧化态分布主要与酸度和还原剂浓度有关。在 ｐ Ｈ 为 ２０ 的葡萄糖酸钠介质中, Ｒｅ Ｏ４－ 首先被亚锡还原为＋ ５ 价,进一步还原至＋ ４ 价和＋ ３ 价;反应介质的 ｐ Ｈ 值越低, Ｒｅ Ｏ４－ 可被还原至更低价态。     

~(188)Re诱发人离体外周血淋巴细胞染色体畸变的初步研究

将人离体外周血在不同剂量的188ReO- 4中培养 5 4h ,观察淋巴细胞有丝分裂中期的染色体型和单体型畸变 ,这两种类型的畸变均有随188Re活度的增高而增加的趋势 ,并与活度存在一定的依赖关系 ,染色体畸变以二次多项式的模式为佳。单体型畸变、畸变细胞、染色体断片也可配以直线回归。     

放射性药物~(188)Re标记DTPA的制备和在大鼠体内的分布

球囊导管内充盈β放射性核素防治经皮冠状动脉成形术(PTCA)后再狭窄是一种崭新的技术, 其中,188Re是一种常用的放射性核素。为了尽可能降低在万一球囊破裂的情况下高剂量放射性对人体的损害,利用二乙三胺五醋酸(DTPA)迅速从泌尿系统排出的特点,通过探索188Re标记DTPA的方法和条件,成功地制备了188Re-DTPA化合物,并研究出最佳的标记条件从而使标记产率达到90%以上。188Re-DTPA和188ReO4-在大鼠体内分布的研究结果显示,甲状腺和胃肠道的放射性水平188Re-DTPA组明显低于188ReO4-组,188Re-DTPA经肾脏排泄明显快于188ReO4-,用MIRDOSE 3.0软件估算体内重要脏器的吸收剂量同样也显示了这一结果。188Re-DTPA组和188ReO4-组甲状腺的吸收剂量分别为0.041 nGy/Bq和0.563 nGy/Bq,胃的吸收剂量分别为0.043 nGy/Bq和0.118 nGy/Bq。因此,实验结果认为在血管内照射治疗中188Re-DTPA明显优于188ReO4-。     

Na188ReO4溶液活度测量的标准化研究

摘要：治疗用放射性药品活度与其用药安全性和有效直接相关。为了确保含188Re放射性药品用药安全有效,本工作利用Na188ReO4溶液,对使用活度计测量Na188ReO4 溶液活度的方法进行了标准化研究。利用4π液闪、4πβ-γ符合方法,通过三家单位4套装置测量,确定Na188ReO4溶液标准源的活度量值;再利用已知活度的标准源,对使用活度计测量Na188ReO4 溶液活度的方法进行了标准化研究,确定了测量条件;最后在三个地区的10台不同活度计上进行了活度测量比对试验,结果表明,利用CRC系列活度计测量Na188ReO4溶液活度,各测定值均在标准值的±3%以内。因此,进行标准化标定后,活度计适于测量Na188ReO4溶液的活度。     

Na188ReO4、188Re-DTPA和188Re-MAG3的生物分布及排泄比较

为比较Na^188ReO4、^188Re-DTPA和^188Re-MAG3在冠状动脉再狭窄防治中的优劣,将这三种放射性药物注入到ICR小鼠和SD大鼠体内,观察其在小鼠体内的分布及在大鼠体内的排泄动力学.结果显示,^188Re-MAG3在小鼠体内的血液清除明显快于^188Re-DTPA和Na^188ReO4,并且在各主要组织脏器的吸收也明显低于^188Re-DTPA和Na^188ReO4.注射后2 h,77.28%的^188Re-MAG3经尿液排出体外,而此时^188Re-DTPA 和Na^188ReO4的尿液排出量不到注射剂量的50%.188Re-MAG3在动物体内的行为明显优于^188Re-DTPA和Na^188ReO4,更适于冠状动脉再狭窄的防治.     

Effect of ~(188)Re on chromosome aberration in humanperipheral blood lymphocytes

1 INTRODUCTIONAlong with the recent development on r a di op harma c e ut ic al s ) th e r a di onu oh d e s ofrheniUm are widely used for cure of tumor and pain-reducing of cancer patients withbone metastases. Because of its excellent nuclear property, rhenium-188 have been takeninto accoUnt much more in nuclear medicine and were used for treatmellt of cancel. Thehajf-life of lssRe is 16.9h. Its beta ray energy is suitable for tumor therapy with arange in tissue Of 4rum. Its small amoU…     

用反符合方法测量131I和133Ba的比活度

¹³¹I是核医学应用中较为重要的核素之一;¹³³Ba是1种电子俘获核素,对HPGeγ谱仪能量刻度和效率校准具有重要意义。利用4πβ(PPC)-γ(HPGe)反符合测量装置对上述两种核素的活度进行了反符合测量方法研究,所得到的比活度测量结果分别为1794.8（1±0.6%）kBq•g^-1（k=1）和502.8•（1±0.6%）kBq•g^-1（k=1）,与归一到相同参考时刻4πβ(PC)-γ(NaI(Tl))符合效率外推法的测量结果1797.6（1±0.5%）kBq•g^-1（k=1）和504.9（1±0.6%）kBq•g^-1（k=1）均在不确定度范围内一致。     

NaI(Tl)探测器的源几何特性对峰总比影响模拟研究

利用蒙特卡罗工具Geant4模拟了~(137)Cs和~(60)Co这两种放射源的几何形状以及探测距离这两个因素对γ射线在NaI(Tl)闪烁体探测器内能量沉积的影响。研究结果表明,当放射源的几何形状不一样时,不同的核素在峰总比达到最大时的探测距离不一样,模拟结果为放射性测量提供了参考。     

CEA、CA19-9、CA72-4、MG-Ag单项及联合检测对诊断胃癌的临床价值

选用CEA，CA19－9，CA72－4，MG－Ag四项肿瘤标志物，应用IRMA进行单项及联合检测，从而为胃癌的早期诊断提供依据，检测结果表明：单项检测阳性率均＞70％，但以MG－Ag阳性率最高（90．4％），次为CA72－4（84．2％），两两组合进行双项联合检测，按双阳性分析，结果显示MG＋CA72－4组合阳性率最高（70．6％），MG＋CA19－9组合次之（64．6％），因此，单项筛选检测，首先MG－Ag；双项组合检测首选MG＋CA72-4为宜，随访可按组织学类型选用适宜的双项组合检测法。