中枢神经系统5—羟色胺受体显像剂WAY类似物的研究进展

阐述了WAY类似物在中枢神经系统5－羟色胺（5－HT）受体显像剂方面的研究状况,介绍了这类化合物在中枢神经系统5－HT受体显像剂方面的优越性,并对^99Tc^m标记WAY类似物受体显像剂的研究方法和进展进行了详细的阐述。     

18F标记乏氧组织显像剂的研究进展

乏氧组织显像剂是当前放射性药物研究的热点之一。随着PET显像技术的迅速发展，^18F标记的放射性药物在临床上的应用越来越广泛。^18FMIO(^18F-氟米索硝唑)是现今核医学领域研究最多的^18F标记的乏氧组织显像剂，它自身存在一些缺点，而新的乏氧组织显像剂仍在进一步的研究中。     

两种~(18)F标记多肽方法的对比研究

具有生物活性的多肽类药物是目前医用放射性诊疗药物研发的一个热点,开辟了核医学分子影像剂的一个新领域。受体特异性的活性肽具有较好的药代动力学特性,且容易进行结构修饰和放射性标记,受到受体显像和肿瘤靶向性定位领域研究人员的广泛关注。一些多肽类放射性药物已经用于临床及临床前试验,且大量的多肽正有待开发。多肽的放射性标记技术经过多年的发展,已经建立起了系统的方法。通过这些方法获得的放射性药物不会影响多肽的生理活性。本文选用了两种18F标记多肽的方法,通过标记条件、放化产率、标记物的比活度、放化纯度、稳定性及荷瘤鼠体内分布等方面对两种标记方法进行比较研究,为18F标多肽类放射性药物的研究提供借鉴。     

关于开展^123Ⅰ标记药物开发的调研

^123Ⅰ放射性核素在临床中的用量占加速器生产放射性同位素的13％，排名第3，仅位于^18F（45％）和^201T1（27％）之后。目前，用于研究和应用的^123Ⅰ标记的放射性药物主要有神经系统诊断用^123Ⅰ标记的显像剂、心血管系统诊断用^123Ⅰ标记的显像剂、^123Ⅰ标记的肿瘤显像剂和^123Ⅰ标记的肾功能显像剂等几大类。     

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.     

肿瘤受体显像剂99Tcm-octreotide的放化纯度分析

采用高压液相色谱分析(HPLC)和双层析结合银染色两种方法，对新型肿瘤受体显像剂^99Tc^m—oc—treotide的放化纯度进行分析。结果表明，双层析法结合银染色可以准确、有效地分离^99Tc^m—octreotide及其它放射性组分，可以较精确地计算出显像剂的放化纯度。为Octreotide及其它多肤类显像剂的放化纯度测定提供了一种简捷、准确的新手段。     

叶酸在放射性核素标记研究中的应用

叶酸在人体内有重要的生理功能,它能特异性结合过度表达于许多肿瘤（卵巢癌、乳腺癌、直肠癌等）细胞膜表面的叶酸受体.在肿瘤靶向药物输运体系中,包括输运放射性核素标记的叶酸螯合物显像剂,叶酸受体是一种潜在的分子靶.近年来,有关放射性核素标记的叶酸螯合物显像剂的研究越来越多.本文着重介绍了放射性核素^111In、^67Ga和99Tc^m（Re）标记叶酸的螯合物显像剂以及它们在肿瘤诊断方面的临床应用.这些资料表明,99Tc^m标记叶酸的螯合物是一种比较有发展前途的显像剂.     

c-Gluc-Lys(［Fe18F］NOTA)-TOCA的制备及初步生物学评价

生长抑素类似物与肿瘤细胞上的生长抑素受体（SSTR）能够特异性地结合。因此,用¹⁸F标记的生长抑素类似物可作为肿瘤示踪剂对生长抑素受体阳性肿瘤进行诊断、分期和疗效评价。为开发一种可用于生长抑素受体阳性肿瘤诊断、能够高效快速合成的¹⁸F标记生长抑素类似物,本文用Fe¹⁸F复合物和偶联了双功能螯合剂1,4,7-三氮环壬烷-1,4,7-三乙酸（NOTA）的糖基化生长抑素类似物c-Gluc-Lys(NOTA)-TOCA通过螯合反应制备了c-Gluc-Lys(［Fe¹⁸F］NOTA)-TOCA,放化反应合成时间为25～30 min,标记率为40%,最终产品经HLB柱纯化后放化纯大于95%。标记物亲水性良好（lg P＝-4.18±0.15）,但体外稳定性差。正常鼠体内分布实验表明：标记物主要通过肾代谢,肝中摄取很低,在生长抑素受体高表达的胰腺中有高摄取,血液和肌肉本底低,骨中摄取高。本工作为进一步研究¹⁸F金属复合物标记的生长抑素类似物作为生长抑素受体阳性肿瘤显像剂提供了实验依据。     

生长抑素类似物^99Tc^m-EDDA／HYNIC-Lys^0-TOCA的标记及动物实验

本工作设计合成了新的生长抑素类似物^99Tc^m-EDDA／HYNIC-Lys^0-TOCA，并对其进行正常小鼠及荷瘤裸鼠体内分布和显像的初步研究，以探讨^99Tc^m-EDDA／HYNIC-Lys^0-TOCA作为生长抑素受体阳性肿瘤显像药物的可能性。     

糖基化生长抑素的125I标记及生物分布

以天然生长抑素、葡聚糖和酪胺为原料，合成了糖基化生长抑素（生长抑素-葡聚糖-酪胺）；以^125I-奥曲肽（^125I-Tyr^3-Octreotide）为放射配基，进行受体竞争结合实验，测定了糖基化生长抑素的IC50；并观察了^125I标记的糖基化生长抑素在正常SD大鼠体内的分布和血液清除状况。结果表明：糖基化的生长抑素保持了对生长抑素2型受体的高亲和力；其IC50与Octreotide相近，^125I标记的糖基化生长抑素血液半减期为6．7h，主要浓聚肝、脾脏并经肾排泄，肾上腺具有较高的放射性摄取，且24h内基本保持不变^125I标记的糖基化生长抑素对生长抑素受体阳性组织具有靶向性。     

~(68)Ga标记放射性药物的制备及应用研究进展

<正>电子发射计算机断层显像(positron emission tomography,PET)为核医学领域的显像方法之一,广泛应用于肿瘤研究,灵敏度高,分辨率佳。近年来,~(68)Ge/~(68)Ga发生器的开发促进了~(68)Ga标记的PET显像药物的研究和应用。~(68)Ga放射性药物主要应用于肿瘤显像,如生长抑素受体、人表皮生长因子受体、叶酸等受体分子的靶向显像;也可用于心肌灌注、肺灌注和通气、炎症和感染显像等。本文主要介绍~(68)Ga标记放射性药物相关的生产,标记涉及的受体及衍生物,以及显像研究等应用进展。     

Preparation of 18F Labeled Octreotide Derivatives18F-Ta-Gluc-TOCA byClick Chemistry and its Biological Evaluation

The preparation of ¹⁸F labeled peptides usually needmany reaction steps, long time, harsh reaction conditions, which greatly limitsthe application of ¹⁸Flabeled PET probe. Using click chemistry for the synthesis of ¹⁸F labeled peptides make thereaction conditions more reliable, efficient and selective. The reactionconditions are mild, low cost, and fast. The purpose of this research was tosynthetize the glycosylated octreotide derivative quickly and easily, todevelop a method of ¹⁸Flabeled peptides by click chemistry. We also discussed the exploration of thefeasibility with ¹⁸Flabeled glycosylated octreotide derivatives as a somatostatin receptor positivetumor probe. This work prepared 2-¹⁸F-azide ethane precursor compounds by nucleophilic substitution and then labeledPr-Gluc-TOCA by click chemistry, finally we got the product ¹⁸F-Ta-Gluc-TOCA by purification.In addition, the in vitro stability and octanol water partition coefficient of ¹⁸F-Ta-Gluc-TOCA were measured.The biodistribution studies of ¹⁸F-Ta-Gluc-TOCAin normal mice and tumor bearing nude mice were investigated. The radiochemicalpurity of ¹⁸F-Ta-Gluc-TOCAwas 91%. The vitro stability was good. The octanol-water partition coefficientwas -0.43±0.05.The results of biodistribution in normal mice showed rapid clearance fromblood, and excreted mainly through the hepatobiliary metabolism, and also throughthe renal metabolism. The results of the biodistribution in tumor bearing nudemice showed high uptake in the tumor (4.34±0.47%ID/g, 60 min). The findings suggest that ¹⁸F-Ta-Gluc-TOCA is a potentialradiotracer for PET imaging of somatostatin receptor positive tumors.     

Radiation dose to patients from radiopharmaceuticals (addendum 2 to ICRP publication 53)

A joint Task Group of ICRP Committees 2 (Doses from Radiation Exposures) and 3 (Protection in Medicine; lead Committee for this report) has prepared a compilation of data on radiation dose to patients from radiopharmaceuticals. The report provides biokinetic models, absorbed doses, and effective doses, using ICRP Publication 60 dosimetry, for 10 new radiopharmaceuticals: [Methyl-11C]thymidine; [2-11C]thymidine; 14C urea (incl. carbon dioxide and bicarbonate); 15O water; 99mTc HIG, Pertechnegas, Technegas, and tetrofosmin; and 111In HIG and octreotide. It also provides recalculated dose data for the 19 most frequently used radiopharmaceuticals from ICRP Publication 53, using ICRP Publication 60 dosimetry, viz. 18F FDG; 51Cr EDTA; 67Ga citrate; 75Se SeHCAT; 99mTc DMSA, DTPA, RBC, IDA, large colloids, WBC, MAA, non-absorbable markers, pertechnetate, and phosphates and phosphonates; 123I Hippuran and MIBG; 131I Hippuran and NP59; and 201Tl thallous ion. Printing errors detected in ICRP Publication 53 are also listed. Furthermore, the report reproduces with minor corrections and updates, and therefore supersedes, the information on 6 radiopharmaceuticals given in Addendum 1 to ICRP Publication 53: 3H neutral fat and fatty acids; 14C neutral fat and fatty acids; 68Ga EDTA; and 99mTc HM-PAO, MAG3, and MIBI. There is an integrated index to all radiopharmaceuticals treated in ICRP publications so far, including a listing of effective doses per unit activity administered to adults. This issue of the Annals of the ICRP also includes an Addendum to ICRP Publication 72 concerning age-dependent doses to members of the public from intakes of radionuclides.     

Comparative assessment of application of low melting metals with capillary pore systems in a tokamak

Capillary-pore systems (CPS) with liquid metals are considered as advanced plasma facing material for application in DEMO-type fusion reactor. The estimation of opportunity of liquid Li, Ga and Sn application is carried out on the basis of its physical, chemical and technological properties, and with respect to prospective design of the tokamak in-vessel elements and technology.It has been shown that Li now is the most attractive and most investigated liquid metal for fusion devices application with CPS. The temperature limit for normal operation is about 550 °C and determined by appropriate Li flux to plasma due to evaporation. Wide range of structural materials is appropriate for Li based in-vessel elements.Ga and Sn are very corrosive and embrittlement inducing metals. As a result the temperature limit of these application is determined by compatibility with structural materials of CPS and in-vessel element. Only W can be used with Ga and Sn up to 500 °C. Moreover these metals have lower thermal properties comparing to Li.Surface temperature analysis for possible in-vessel element design (1 mm thick of porous W based CPS) has shown the similar power flux limit ∼21 MW/m² for Li, Ga and Sn application at normal operation. Taking into account the latent heat of vaporization and screening effect with re-radiation the CPS with Li has a priority at ELM and disruption conditions.     

Surface Ionization Ion Sources

Recent achievements with iridium surface ionization ion sources are discussed. These sources can be used to produce ion beams of elements with ionization potentials from 5-1/2 to 6 V, e. g., the IILA metals (Al, Ga, In and Tl), the rare earths, the heavier alkaline earths, and Li, in addition to the usual heavier alkalis. Ion beams of Li, Al, Ga, and In have been produced here. Ionization efficiencies, critical temperatures, current densities, and beam purities as measured by magnetic mass separation are discussed. An ion source design being employed for the IIIA metals is described briefly.     

氮杂大环化合物在放射性金属标记中的应用研究进展

氮杂大环化合物可作为双功能螯合剂标记生物分子(一般为小肽,蛋白质或单克隆抗体等),这些放射性金属标记的生物分子为核医学提供了具有广阔应用前景的放射性诊断和放射性治疗药物。综述了氮杂大环化合物在放射性金属标记中的应用研究最新进展,介绍了用于标记的氮杂大环化合物,用于标记的放射性核素,以及标记物的生物学特性。并指出了氮杂大环化合物在不同核素标记中的优缺点。     

Peptides radiolabelled 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.     

生长抑素-葡聚糖的99Tcm标记及体外结合分析

采用还原氨化方法，将天然生长抑素（SMS）与葡聚糖(Dx20)偶联，并以125I－奥曲肽（125I-Tyr3-Octreotide)为放射配基，进行受体竞争结合实验，测定了SMS-Dx50的IC50；以SnCl2为还原剂对SMS-Dx50进行99Tcm标记，并进行99Tcm- SMS-Dx50受体结合分析，考察其对生长抑素受体的亲合能力。结果表明：SMS-Dx50保持了对SMS 2型受体的高亲和力；其IC50与奥曲肽的IC50（0.79 nmol/L）相近,为5.95 nmol/L；99Tcm- SMS-Dx50标记率>85％, 经PD-10柱分离纯化，其放化纯度>98%；99Tcm- SMS-Dx50对生长抑素2型受体特异性结合为25%～40％，保持了较高的亲和力；SMS-Dx50适合于99Tcm标记，可用于生长抑素受体阳性肿瘤诊断的进一步研究