生长抑素及其类似物的标记技术的发展

生长抑素受体显像剂是临床上应用最为普遍的放射性多肽类受体显像剂。用多种放射性同位素^111In、^90Y、^6Ga、^68Ga、^64Cu或是用^99Tc^m、^188Re以及卤族同位素^123I、^18F等对奥曲肽及其类似物进行标记得到的放射性多肽药物，已广泛用于临床显像。介绍了生长抑素类似物及标记技术的发展，对目前临床上比较成熟的生长抑素类显像剂做了综述和比较。同时介绍了目前在SST类似物开发领域及生物行为研究领域中的最新发展动态。     

Radiosynthesis and biodistribution of [^18F]-tetracosactide using a semi-automated [^18F]SFB production module

In order to prepare a specific melanocortin type 2 receptor (MC2R) ligand, b1-24-corticotrophin was pre-pared in one-step reaction with [18F] SFB and b-1-24-corticotrophin pharmaceutical solution (1 mg/mL, pH=6.5). [18F]SFB was prepared in a semi-automated module in two steps with an overall radiochemical yield of 47% to EOB (not-decay corrected) in 90 min. The 18F-labeled intermediates and 18F-labeled peptide was checked by RTLC and HPLC. The results show that the radiochemical purity is >95% and the yield to EOB (not-decay corrected) is 29% for final 18F-labeled peptide at optimized conditions. Preliminary in vivo studies in normal mice were performed to deter-mine biodistribution of the 18F-labeled peptide for 150 min. The results show that the major tracer uptake is consistent with the natural distribution of MC2R receptors in mammals. Testes/blood and testes/muscle ratios for 18F-labeled peptide at 150 min were 184 and 1.56, respectively, and adipocyte/blood and adipocyte/muscle ratios at 120 min were 221 and 142, respectively. The data support the specific receptor binding of the radiolabeled peptide as reported for MC2R receptor accumulation in adipocytes and testes and demonstrates the retention of biological activity of the pep-tide. This tracer can be used in detection of MC2R distribution in malignancies and sex organ diseases.     

^212Pb,^212Bi标记金属硫蛋白

研究了用２１２Ｐｂ、２１２Ｂｉ和２１２Ｐｂ－２１２Ｂｉ平衡混合物分别标记金属硫蛋白Ｃｄ－ＭＴ２及这些标记物在ＳｅｐｈａｄｅｘＧ－１００柱上的淋洗行为和衰变趋向。实验结果表明，在生理ｐＨ条件下，Ｃｄ－ＭＴ２首先与２１２Ｂｉ结合，其标记率接近１００％。     

188Re-MAG3的制备及动物体内评价

本工作着重研究了可用于PTCA(Percutaneous transluminal coronary angioplasty)后冠状动脉再狭窄防治的放射性标记化合物^188Re-MAG3的制备,并与Na^188ReO4的小鼠体内生物分布加以比较。结果表明,在 TechneScan MAG3锝药盒中加入酒石酸亚锡,控制标记条件,^188Re-MAG3的标记率可大于98％。^188Re-MAG3在小鼠体内的血液清除明显快于Na^188ReO4,甲状腺和胃肠道吸收明显低于Na^188ReO4,标记物主要经肾脏通过尿液排出体外。为降低PTCA后冠脉再狭窄的发生率,与Na^188ReO4相比,^188Re-MAG3更适于临床应用。     

125I-interleukin-8 radiolabelling and in vivo distribution

1 Introduction Interleukin-8(IL-8) is expressed as a 99 aminoacid protein by monocytes, endothelial cells, fibro-blasts and many cell types of epithelial origin. Fol-lowing cleavage of a signal peptide and further prote-olytic processing at the ami…     

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 125I-Cas9 of high labeling yield.The prepared 125I-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.     

Directly radiolabeled phage with spleen-targeting specificity

Phage display technique is a powerful approach for discovering new tumor-and organ-targeting ligands,and radiolabeled phage has a potential to analyze the phage-binding sensitivity and specific imaging.In this study,phage Ⅱ (the spleen-targeting phage) in mice was isolated after three rounds biopanning,and labeled by 99mTc using mercaptoacetyltriglycine (MAG3) as chelator to evaluate their binding properties in vivo.The amount of phage Ⅱ eluted from spleen was enriched by plague assay each round.99mTc-MAG3-phage Ⅱ showed the less retention in blood at any time point than half that of 99mTc-MAG3-phage Ⅰ (the radiolabeled original Ph.D-12 phage as control).The accumulation in spleen between 99mTc-MAG3-phage Ⅰ and Ⅱ was of different tendency.The highest uptake of 99mTc-MAG3-phage Ⅱ in spleen was 24.80 %ID/g at 30 min;and of 99mTc-MAG3-phage I,30.93% ID/g at 5 min.After circulating 99mTc-MAG3-phage Ⅱ for 120 min,its accumulation in spleen decreased though higher than that of 99mTc-MAG3-phage Ⅰ.In other organs,the 99mTc-MAG3-phage Ⅱ showed low retention and high spleen-to-organ or tissue ratios.In conclusion,the radiolabeled phage Ⅱ is convenient for studying the binding and specificity of spleen-targeting peptides found via phage display in vivo.     

Magnetic 99mTc- core-shell of polyethylene glycol/polyhydroxyethyl methacrylate based on Fe3O4 nanoparticles: Radiation synthesis,characterization and biodistribution study in tumor bearing mice

Magnetic nanoparticles (Fe₃O₄) coated with polyethylene glycol (PEG), (Fe₃O₄/PEG), were synthesized by chemical co-precipitation of Fe²⁺/Fe³⁺ salts by aqueous ammonia in PEG solution. Radiation polymerization of 2-hydroxyethyl methacrylate (HEMA) monomer solution onto Fe₃O₄/PEG was performed at different doses to synthesize (Fe₃O₄/PEG)-pHEMA, namely FPH, nanocomposites. Properties of FPH nanocomposites were characterized by FT-IR, XRD, SEM, TEM, DLS, ESR and TGA techniques. The XRD of FPH nanocomposites showed all the peaks of Fe₃O₄ nanoparticles. SEM was used to assess the surface morphology of FPH. TEM showed that the average diameter of FPH nanocomposites was in the range of 9–40 nm. The thermal stability of FPH nanocomposites was higher than that of Fe₃O₄ and Fe₃O₄/PEG. Radio-labeling of (Fe₃O₄/PEG)-pHEMA nanocomposite irradiated at 10 kGy (FPH10) with ^99mTc was performed using stannous chloride as reducing agent. Factors affecting the labeling yield (%) such as the substrate amount, the amount of reducing agent, the pH of reaction medium, the reaction time and the reaction temperature were investigated. The maximum labeling yield was 93% using 0.25 mg of FPH10 at pH 6 and 20 min reaction time. The biodistribution study of ^99mTc-FPH10 was examined on two groups of ascites and solid tumor bearing mice. The biodistribution results referred that ^99mTc-FPH10 was rapidly uptake in tumor sites ascites or solid tumors. The results indicated that FPH nanocomposites could be potentially used for tumor imaging and therapy.     

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。     

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.