红细胞^99Tc^m体外标记法的研究

建立了红细胞＾９９Ｔｃ＾ｍ体外标记法。研究了Ｓｎ（Ⅱ）含量，Ｓｎ（Ⅱ）温育时间，＾９９Ｔｃ＾ｍ标记时间，ＮａＣｌＯ和Ｎａ２ＥＤＴＡ用量以及＾９９Ｔｃ＾ｍ和血液体积等红细胞标记率的影响，确定了最佳标记条件并已药盒化。     

^99mTcN（DDC）2的制备及生物分布

用＾９９ｍＴｃＮ中间体制得的＾９９ｍＴｃＮ（ＤＤＣ）２经ＴＬＣ检测放化及标记率均大于９０％，标记物在ＰＨ７．４时的分配系数是１４２７。小鼠体内分布研究表明５、３０、６０ｍｉｎ时的心肌摄取分别为２．６４、１．０６、０．５９％ＩＤ，脑摄取分别为１．３０、０．５６、０．３２％ＩＤ。     

^99Tc^m标记的中枢神经系统受体放射性药物的设计方法及进展

综述了99Tc^m标记中的中枢神经系统受体放射性药物目前的进展,着重讨论了不同受体放射性药物的设计方法及存在的问题。     

新的心血池显像剂^99Tc^m—DTPA—HSA的实验研究

＾９９Ｔｃ＾ｍ－ＤＴＰＡ－ＨＳＡ心血池显像剂于２０只家兔进行实验研究，并与＾９９Ｔｃ＾ｍ－ＲＢＣ（体内法）及＾９９Ｔｃ＾ｍ－ＨＳＡ进行比较。由＾９９Ｔｃ＾ｍ＝ＤＴＰＡ－ＨＳＡ所得心血池显像的图像清晰。生物学分布研究表明，＾９９Ｔｃ＾ｍ－ＤＴＰＡ－ＨＳＡ在肝和肺的浓聚较＾９９Ｔｃ＾ｍ－ＲＢＣ及＾９９Ｔｃ＾ｍ－ＨＳＡ略低。心／肝放射性比值，＾９９Ｔｃ＾ｍ－ＤＴＰＡ－ＨＳＡ为０．８５，＾９９Ｔｃ＾ｍ－Ｒ     

C60衍生物的放射性碘标记

富勒烯C60是由60个碳原子组成的球型分子,包含12个五元环和20个六元环,直径为0.71nm.独特的结构赋予了它特殊的物理、化学和生物性质.C60是一个优良的电子接受体,通过光诱导产生单重态氧的效率高达100%,被喻为"单重态氧的发生器”.它极易与游离基反应,又被喻为"吸收游离基的海绵”.它具有30个双键,可以发生许多有机反应,连接各种化学药物,是药物设计的理想载体[1].C60仅溶于一些非极性和弱极性的有机溶剂,在水等极性溶剂中不溶.富勒烯作为药物载体,首先要制成水溶性衍生物.更为重要的是还必须了解它及其衍生物的基本药理性质,但这方面研究刚刚开始,研究结果报道甚少,其中一个原因是缺少对富勒烯及其衍生物的分析检测方法.Yamago[2]曾用14C标记C60衍生物,但由于14C核性质并不理想而且标记方法颇为复杂,其应用范围和研究结果均受限制.由于C60具有双键,可以进行碘标记.本工作制备了水溶性富勒烯衍生物C60(OH)xOy,然后采用Iodogen氧化法用125I标记了该衍生物,为今后药理研究,例如,在动物体内的吸收、分布、排泄、毒性等研究创造了条件.     

^99Tc^m直接标记单克隆抗体的研究：I.用^99Tc^m标记Fab（3H1…

总结了一种简便，可靠的直接标记法，并成功地运用此法对含巯基较少的Ｆａｂ片段进行了标记，得到了很好的标记率和体外稳定性以及较好的对荷瘤裸鼠的体内分布和显像结果。     

新型肾功能显像剂^99mTc—MAG3的合成及动物实验

由三甘氨肽与氯乙酰氯、苯甲硫羟酸反应得到^99mTc-MAG3的前体化合物BZ－MAG3，并用^99mTc标记，即得^99mTc-MAG3，标记率达97％。经动物实验表明：^99mTc-MAG3能以原形快速经肾排泄。     

Study of99Tcm-Annexin V Distribution in Inferior Vena Cava Thrombus Models of Rabbits

To study⁹⁹Tc^m-Annexin V distribution in inferior vena cava thrombus models of rabbits and uptake of⁹⁹Tc^m-Annexin V in fresh and old venous thrombus. Rabbits(n=15) were randomly grouped into 3 groups(the fresh thrombus group,old thrombus group,and control group). The rabbits of two thrombus groups developed inferior vena cava thrombus models by operations. The control group received sham operation. The fresh thrombus group and control group rabbits were injected⁹⁹Tc^m-Annexin V after operating 1d; the old thrombus group 14 d. After 1 h all rabbits were killed by injecting overdose pentobarbital sodium. The thrombus (or the inferior vena cava about 3cm below inferior pole of right kidney level in the control group rabbits),blood,thrombus area inferior vena cava,head lateral inferior vena cava (except the control group),thigh muscle,stomach,myocardium,pulmonary,liver,kidney,spleen,bone and small intestine were obtained from all group rabbits. The ex tissue and blood were weighed and measured by a Well-type detector. The percentage of the injected dose per gram of ex tissue (or blood) was calculated by the above data. The thrombus to blood,thrombus area inferior vena cava,head lateral inferior vena cava and thigh muscle ratios were calculated by percentage of the injected dose per gram of ex tissue (or blood) . The test was used to compare the fresh thrombus group and old thrombus group by SPSS 17.0. The percentage of the injected dose per gram of thrombi（0.018 94±0.002 16%ID/g）in the fresh thrombus group was higher than the old thrombus group (0.004 73±0.001 28%ID/g), P<0.05. The thrombus to blood,thrombus area inferior vena cava,head lateral inferior vena cava and muscle ratios (3.42±1.06,26.32±13.60,31.23±16.00,111.62±52.23) in the fresh thrombus group were higher than the old thrombus group(0.98±0.09,5.12±2.01,6.25±2.38,21.82±5.93) ,P<0.05 for all. All the thrombi of the fresh thrombus group were confirmed fresh mixed thrombi by Hematoxylin-eosin stains. All the thrombi of the old thrombus group were confirmed old mixed organized thrombi by Hematoxylin-eosin stains. ⁹⁹Tc^m-Annexin V may be used to venous thrombus imaging and discriminate fresh venous thrombus from old one by imaging.     

~(99)Tc~m(CO)_3-BPHRGD的制备及其在荷M21人黑色素瘤裸鼠体内的生物分布

制备了99 Tcm(CO)3-BPHRGD,并进行了荷M21人黑色素瘤裸鼠体内生物学评价。在pH=7、75℃条件下反应30min,99 Tcm(CO)3-BPHRGD的标记率大于80%,纯化后标记物的放化纯度大于98%。体外稳定性实验结果显示,37℃下,标记物在生理盐水、人血清中具有很好的稳定性。荷M21人黑色素瘤裸鼠体内分布显示,注射99 Tcm(CO)3-BPHRGD后0.5、1、2、4h,标记物的瘤/血比分别为0.70±0.45、0.87±0.05、1.10±0.19、1.68±0.04。随着时间的延长,靶与非靶的放射性摄取比(T/NT)增大,表明该标记物在肿瘤细胞中的清除速度慢于其他组织。通过进一步结构修饰,改变其体内代谢途径及药代动力学性质,99 Tcm(CO)3-BPHRGD非常有希望成为一种新型肿瘤显像剂。     

^99Tc^m—MIBI肿瘤阳性显像的临床应用

探讨了^99Tc^m-MIBI肿瘤阳性显像在多种恶性肿瘤临床诊断中的应用价值。静脉注射^99Tc^m-MIBI 15～30min后,用美国GE公司SPX-6型SPECT行病变局部平面和断层显像,计算肿瘤与本底比值（T/B）,当T/B≥1.5时判定显像结果为阳性;肝脏肿瘤诊断则比较胶体显像和阳性显像时肿瘤部位是否有填充,若有填充则为阳性。21例受检者中病理诊断为恶性肿瘤17例,良性肿瘤4例。17例恶性肿瘤^99Tc^m-MIBI阳性显像15例阳性,2例阴性;4例良性肿瘤患者显像结果均为阴性。本组病例^99Tc^m-MIBI阳性显像的敏感性为88%,特异性为100%,阳性预测值为100%,阴性预测值为66.7%,准确率为90%。结果表明^99Tc^m-MIBI阳性显像诊断和鉴别诊断良恶性肿瘤具有良好的临床应用前景。     

~(99)Tc~m(CO)_3-BPHRGD的制备及正常鼠体内生物分布

制备了99 Tc m(CO)3-BPHRGD,并进行体内外生物学评价。在pH=7、75℃条件下反应30min,99 Tc m(CO)3-BPHRGD的标记率均大于80%,纯化后标记物的放射化学纯度大于98%;体外稳定性实验显示,在37℃时,标记物在生理盐水、胎牛血清及半胱氨酸溶液中具有很好的稳定性;正常小鼠体内生物分布数据显示,99 Tc m(CO)3-BPHRGD在血液中清除较快,主要通过肝肾代谢。     

^99Tc^m标记5—HT1A脑受体显像剂的研制及其生物分布

为了寻找99Tcm标记中枢神经系统5-HT1A协同受体显像药物,合成了单齿受体配基1-(2-甲氧基苯基)-4-(2-巯基乙基)哌嗪(简称MPMEP)、三齿配体N,N-二(2-巯基乙基)-N',N'-二乙基乙二胺(简称BMPDEEDA)和N,N-二(2-巯基乙基)卞胺(简称BMPBA),其结构经IR、NMR及元素分析表征;以“3+1”混合配体进行了99Tcm标记,并确定了标记反应的最佳条件pH=6.0～7.0,60～70℃下,反应20～30min,经CH2Cl2萃取脂溶性部分后,99TcmO(MPMEP)(BMPDEEDA)和99TcmO(MPMEP)(BMPBA)的标记率分别达到95%和90%以上.采用HPLC对标记产物进行了分离和纯化,纯化后的标记物放化纯度均>98%.小鼠体内的生物分布结果表明99TcmO(MPMEP)(BMPDEEDA)和99TcmO(MPMEP)(BMPBA)配合物可以通过血脑屏障,在脑中有一定的摄取和滞留;99TcmO(MPMEP)(BMPBA)在血液中清除较快,静脉注射后2、30、60min时,脑与血摄取比分别为0.31、0.33、0.32,但血液中放射性活度仍然较高.     

O NMR study in (Pu0.91Am0.09)O2

In order to investigate the magnetic properties of Am⁴⁺ ions in the cubic fluorite structure, we have performed ¹⁷O NMR measurements on (Pu_0.91Am_0.09)O₂. We have observed a temperature-dependent ¹⁷O NMR line broadening induced by classical dipolar hyperfine fields from the Am 5f moments. From NMR line simulations, the effective moment of the Am moments has been estimated to be μ_eff=1.38μ_B/Am. This value is comparable with μ_eff=1.32 or 1.53μ_B/Am reported for AmO₂. We have also carried out nuclear relaxation measurements for ¹⁷O nuclei. The magnetization recovery has been found to exhibit a nonexponential time dependence with an exponent β∼0.5. This result is well understood in terms of the nuclear relaxation mechanism induced by the Am 5f moment fluctuations via dipolar hyperfine fields.     

Na99TcmO4示踪显像监测家兔断肢再植术后血管危象的对比研究

将40只家兔施行断肢再植术后20min随机分为A(25只)、B(15只)两组,A组伤口局部冷敷(＜5℃)、B组热敷(40-45℃)10min,C组(5只正常对照家兔)置于室温(20-25℃).所有家兔耳缘静脉注射Na99TcmO4 74 MBq后行动态和静态显像,计算并分析再植部分和正常肢对应部分的放射性摄取比值(T/NT).手术探查再植肢是否并发血管危象(VC).根据术肢远端放射性聚集程度将显像结果分为O、Ⅰ、Ⅱ三级,结果显示T/NT分别为0.142±0.061、0.472±0.055、0.843±0.184(t=7.23、13.65、2.71,P＜0.01),将O级(T/NT＜0.25)作为VC的定性和半定量诊断标准.手术探查证实A、B、C三组分别有25只、3只、0只家兔并发VC,局部冷敷制备VC动物模型的成功率100%;Na99TcmO4示踪显像(Na99TcmO4 trace imaging,TTI)诊断VC的灵敏度(96.4%),明显高于临床常规方法(Clinical routine method,CRM)(39.3%)(χ2=20.9,P＜0.01).表明TTI较CRM更能直观而准确地反映再植末端的血供状况,能早期无创地监测断肢(指)再植术后VC的发生.     

The pre-dose effect in natural white mica (H2KAl3(SiO4)3)

A comprehensive study of the pre-dose effect was carried out for natural white mica. A pre-dose of 1 kGy of γ-radiation followed by thermal activation to 550 °C of fired mica (heated at 800 °C for 10 h) leads to a large increase in the TL sensitivity. The TL response to γ-rays of sensitized aliquots was found to be linear-sublinear while that of unsensitized aliquots was linear-superlinear referring specifically to graphs drawn on a linear-linear scale. The change in the TL sensitivity of mica was explained by using the recombination during heating model. This study is of importance in dating and retrospective dosimetry.     

Preparation and BiologicalEvaluation of Re/99Tcm(CO)3+-diphenyldiazeneDerivative as Candidates for Imaging Aβ Plaques in the Brain

To develop the non-invasiveand diagnostic agents for Alzheimer’s disease (AD), ⁹⁹Tc^m(CO)₃⁺-L(L: (E)-2-(4-((4-(dimethylamino)phenyl)diazenyl)phenylamino)acetic acid, adiphenyldiazene derivative) was prepared,radiochemical purity was above 95%. Initialautoradiography results suggested that ⁹⁹Tc^m(CO)₃⁺-Lshowed selective binding to the Aβ plaque-like structures in the brain section from theAD transgenic mice (Tg C57, APP, PS1 12-month-old), further, ⁹⁹Tc^m(CO)₃⁺-Lshowed the same binding sites with fluorescence stained by Re(CO)₃⁺-L.Biodistribution of ⁹⁹Tc^m(CO)₃⁺-L innormal mice demonstrated low uptake in brain (5 min: （0.52 ±0.11)% ID/g）whilst slow clearance from the brain tissues at 120 min post-injection (0.28 ± 0.04)%ID/g. The corresponding Re analogue was alsosynthesized, and the nature of its lowest electronically excited state wasdetermined by studies of the UV-vis absorption and fluorescence emissionproperties at room temperature. In addition, the fluorescent staining of the Re-complexwas performed in comparison to Thioflavin-T and autoradiography results of ⁹⁹Tc^m(CO)₃⁺-L.In conclusion, these results are encouraging for further exploration of ⁹⁹Tc^m(CO)₃⁺-Las a SPECT imaging agent for Aβplaques in the AD brain.