低、中能X射线吸收剂量测量中的几个问题

辐射防护剂又称抗辐射药物 ,其研究在 6 0年代后期达到高峰 ,但由于高效、低毒 ,可供临床应用的辐射防护剂较难发现 ,从而对辐射防护剂的期望逐渐淡薄起来 ,70年代明显下降。近年来随着肿瘤放疗的进展及核工业的迅速发展 ,国内外对辐射防护剂的研究热情重新高涨 ,主要表现在整体水平、细胞水平、分子水平、基因水平 4个层次对抗辐射药物作用机理进行深入研究 ;有目的寻找毒性低、疗效高的抗辐射新药 ;重视抗放药物的临床应用 (放疗及其他疾病 )及伍用。细胞因子是当今辐射防护剂的研究热点 ,氨巯基化合物仍是研究中的重要化合物类型 ,其他辐…     

小分子辐射防护药物的研究进展

辐射防护药物能减少辐射损伤，促进损伤恢复，与细胞因子等大分子药物相比，小分子辐射防护药使用方便，没有潜在的免疫原风险。笔者汇总了硫醇类化合物、天然抗氧化剂、氮氧自由基、血管紧张素转化酶抑制剂等几类不同的辐射防护药物，对其辐射防护效果以及作用机制进行了总结、归纳，并对此类药物的研发前景进行了展望，旨在为辐射防护药物的进一步研发提供思路。     

生物样品中多肽药物质谱定量分析方法研究进展

质谱(MS)在药代研究中起非常重要的作用.液质联用技术,由于其特异性好和灵敏度高,被认为是生物样品定性和定量的最有效分析手段.药物研究领域正在开发能够对肽类药物进行绝对定量分析的新技术方法.基于多肽药物的结构及理化性质,本文综述了利用LC-ESI-MS技术对生物基质中多肽药物进行定量分析的特点与难点,重点讨论在药物定量分析中的多种样品处理技术、多肽色谱分离、ESI-MS的重要特点、质谱检测模式的选择、内标的选择以及现代质谱技术等.     

碱性成纤维细胞生长因子对辐射诱导的小鼠胸腺细胞凋亡的抑制作用

碱性成纤维细胞生长因子 (ｂＦＧＦ)作为一种多肽类生长因子 ,有着广泛的生理功能。对中胚层和神经外胚层来源的细胞具有促有丝分裂的作用 ,在胚胎发育和组织分化中 ,是形态形成、促细胞分裂和诱导细胞分化不可缺少的因子[1 ] 。近年来 ,许多实验结果表明体外许多因素 ,如化学药物、细胞因子、辐射等都可诱导细胞凋亡[2 ] 。本研究ｂＦＧＦ对辐射诱导的免疫系统胸腺细胞凋亡的调节作用 ,旨在从一个侧面探讨ｂＦＧＦ作用于免疫系统的机理及其在辐射防护中的意义。一、材料和方法1 ｂＦＧＦ :由暨南大学生物工程研究所提供。2 动物照射 :昆明…     

四种抗放药对组织氧张力的影响

近年来由于对抗放药物药理作用研究的逐步深入,使我们有可能正确认识药物在机体内所引起的一系列动态变化。进一步的研究证明,这些动态变化构成了药物辐射防护作用的物质基础,而且经常是和其辐射防护作用伴随发生,决定药物效价的大小。因此在     

辐射防护药物研究最新进展

电离辐射损伤不仅是一个公众健康问题,同时也是一个国家安全问题。如何获得治疗效果优良、安全性高和不良反应小的辐射防护药物一直是科学家努力研究的目标。近年来,伴随着分子生物学、免疫学等学科的发展,辐射防护药物的研究也取得了较大的突破。目前,诸如5-雄烯二醇（5-AED）、CBLB502、Ex-RAD和HemaMax等药物已获得美国食品药品监督管理局的批准进入临床试验;而新发现的具有潜在价值的LY294002和17-DMAG等药物也正处于研发之中。笔者基于近年来辐射防护领域国外相关刊物和专利的最新发现和进展进行综述。重点放在近几年来出现的药物新进展以及这一时间内治疗急性放射综合征的抗辐射新药上。     

多肽类示踪技术在乳腺癌诊治中的应用进展

核素分子诊治乳腺癌在近几年发展迅速,是研究的热点。放射性核素标记的多肽受体显像是核医学中最年轻、最有活力的分支领域。当前有代表性的前沿多肽类示踪药物包括生长抑素类似物、16α-18F-17β-雌二醇、血管活性肠肽、白细胞介素11类似物环九肽、顺式11β-甲氧基-17α-123I-碘乙烯雌二醇等数种。该文综述各种多肽类药物在乳腺癌诊治中的最新进展。     

多肽类示踪技术在乳腺癌诊治中的应用进展

核素分子诊治乳腺癌在近几年发展迅速,是研究的热点.放射性核素标记的多肽受体显像是核医学中最年轻、最有活力的分支领域.当前有代表性的前沿多肽类示踪药物包括生长抑素类似物、16α-18F-17β-雌二醇、血管活性肠肽、白细胞介素11类似物环九肽、顺式11β-甲氧基-17α-123I-碘乙烯雌二醇等数种.该文综述各种多肽类药物在乳腺癌诊治中的最新进展.     

多肽类示踪技术在乳腺癌诊治中的应用进展

核素分子诊治乳腺癌在近几年发展迅速,是研究的热点.放射性核素标记的多肽受体显像是核医学中最年轻、最有活力的分支领域.当前有代表性的前沿多肽类示踪药物包括生长抑素类似物、16α-18F-17β-雌二醇、血管活性肠肽、白细胞介素11类似物环九肽、顺式11β-甲氧基-17α-123I-碘乙烯雌二醇等数种.该文综述各种多肽类药物在乳腺癌诊治中的最新进展.     

多肽类示踪技术在乳腺癌诊治中的应用进展

核素分子诊治乳腺癌在近几年发展迅速,是研究的热点.放射性核素标记的多肽受体显像是核医学中最年轻、最有活力的分支领域.当前有代表性的前沿多肽类示踪药物包括生长抑素类似物、16α-18F-17β-雌二醇、血管活性肠肽、白细胞介素11类似物环九肽、顺式11β-甲氧基-17α-123I-碘乙烯雌二醇等数种.该文综述各种多肽类药物在乳腺癌诊治中的最新进展.     

蜂产品对放射性损伤的防治研究进展

在军事、医疗和公共卫生方面,辐射暴露是一个持续而严重的威胁。针对辐射引起的损伤需要有效的预防或缓解治疗,但是目前这些问题尚未得到解决。临床上少数食品药品监督管理局（FDA）批准的辐射防护剂副作用大,限制其广泛使用。据报道,一些天然的无毒化合物（如蜂产品）可通过减轻辐射引起的氧化应激、细胞凋亡和DNA损伤来预防和治疗辐射引起的口腔黏膜炎、食管炎、皮肤损伤、肝损伤、肠道损伤和造血系统的损伤等。这表明这些蜂产品有作为辐射防护剂的潜力。本文就蜂产品对防治放射性损伤的实验及临床研究进行综述。     

Advances in Radioprotection through the Use of Combined Agent Regimens

Summary

The most effective radioprotective agents exhibit toxicities that can limit their usefulness. It may be possible to use combinations of agents with different radioprotective mechanisms of action at less toxic doses, or to reduce the toxicity of the major protective compound by adding another agent. With regard to the latter possibility, improved radioprotection and reduced lethal toxicity of the phosphorothioate WR-2721 was observed when it was administered in combination with metals (selenium, zinc or copper). The known mechanisms of action of potential radioprotective agents and varying effects of different doses and times of administration in relation to radiation exposure must be considered when using combined-agent regimens. A number of receptor-mediated protectors and other biological compounds, including endotoxin, eicosanoids and cytokines, have at least an additive effect when administered with thiol protectors. Eicosanoids and other bioactive lipids must be administered before radiation exposure, whereas some immunomodulators have activity when administered either before or after radiation exposure. For example, the cytokine interleukin-1 administered simultaneously with WR-2721 before irradiation or after irradiation enhances the radioprotective efficacy of WR-2721. The most effective single agents or combinations of protectors result in a decrement in locomotor activity, an index of behavioral toxicity. Recent evidence indicates that administration of the CNS stimulant caffeine mitigates the behavioral toxicity of an effective radioprotective dose of the phosphorothioate WR-3689 without altering its radioprotective efficacy. These examples indicate that the use of combinations of agents is a promising approach for maximizing radioprotection with minimal adverse effects.     

Recent progress in fluorine-18 labelled peptide radiopharmaceuticals

The application of biologically active peptides labelled with positron-emitting nuclides has emerged as a useful and interesting field in nuclear medicine. Small synthetic receptor-binding peptides are currently the preferred agents over proteins and antibodies for diagnostic imaging of various tumours. Due to the smaller size of peptides, both higher target-to-background ratios and rapid blood clearance can often be achieved with radiolabelled peptides. Hence, short-lived positron emission tomography (PET) isotopes are potential candidates for labelling peptides. Among a number of positron-emitting nuclides, fluorine-18 appears to be the best candidate for labelling bioactive peptides by virtue of its favourable physical and nuclear characteristics. The major disadvantage of labelling peptides with 18F is the laborious and time-consuming preparation of the 18F labelling agents. In recent years, various techniques have been developed which allow efficient labelling of peptides with 18F without affecting their receptor-binding properties. Moreover, the development of a variety of prosthetic groups has facilitated the efficient and site-specific labelling of peptides with 18F. The 18F-labelled peptides hold enormous clinical potential owing to their ability to quantitatively detect and characterise a wide variety of human diseases when using PET. Recently, a number of 18F-labelled bioactive peptides have shown great promise as diagnostic imaging agents. This review presents the recent developments in 18F-labelled biologically active peptides used in PET.     

Recent progress in fluorine-18 labelled peptide radiopharmaceuticals

The application of biologically active peptides labelled with positron-emitting nuclides has emerged as a useful and interesting field in nuclear medicine. Small synthetic receptor-binding peptides are currently the preferred agents over proteins and antibodies for diagnostic imaging of various tumours. Due to the smaller size of peptides, both higher target-to-background ratios and rapid blood clearance can often be achieved with radiolabelled peptides. Hence, short-lived positron emission tomography (PET) isotopes are potential candidates for labelling peptides. Among a number of positron-emitting nuclides, fluorine-18 appears to be the best candidate for labelling bioactive peptides by virtue of its favourable physical and nuclear characteristics. The major disadvantage of labelling peptides with ¹⁸F is the laborious and time-consuming preparation of the ¹⁸F labelling agents. In recent years, various techniques have been developed which allow efficient labelling of peptides with ¹⁸F without affecting their receptor-binding properties. Moreover, the development of a variety of prosthetic groups has facilitated the efficient and site-specific labelling of peptides with ¹⁸F. The ¹⁸F-labelled peptides hold enormous clinical potential owing to their ability to quantitatively detect and characterise a wide variety of human diseases when using PET. Recently, a number of ¹⁸F-labelled bioactive peptides have shown great promise as diagnostic imaging agents. This review presents the recent developments in ¹⁸F-labelled biologically active peptides used in PET.     

Recent developments in 99Tcm-labelled peptide-based radiopharmaceuticals: an overview

Nature has designed peptides to stimulate, inhibit or regulate many body functions. The development of radiolabelled peptide-based radiopharmaceuticals for imaging a variety of tumours, infection/inflammation and thrombus has seen a new era in nuclear medicine. Recently, a number of 99Tcm-labelled bioactive peptides have proven to be useful diagnostic imaging agents. Due to their small size, peptide molecules exhibit favourable pharmacokinetic characteristics, such as rapid uptake by target tissue and rapid blood clearance, which potentially allows images to be acquired earlier following the administration of a 99Tcm-labelled peptide radiopharmaceutical. The challenge is to label bioactive peptides with 99Tcm with high specific activity without impairing the biological properties of the peptides. Molecular engineering techniques now permit synthesis of a wide range of biologically active peptides that carry chelating groups in their structure without affecting their receptor binding properties, thus permitting a high specific activity product. This review presents recent developments in 99Tcm-labelled small peptides and their potential applications in the imaging of various types of diseases. In addition, the different techniques for radiolabelling small bioactive peptides, the pharmacokinetic properties of peptides, and their potential as diagnostic imaging agents are also addressed.     

除FDG以外的用于肿瘤PET显像的18F标记物

综述了除FDG以外的用于肿瘤PET显像的18F标记物的研究和应用.这些18F标记物主要包括与相应受体结合的18F标记的蛋白质和多肽,18F标记的乏氧显像剂,用于评价基因治疗的18F标记物等.此外,还介绍了用于诊断不同恶性肿瘤的18F标记的组织特异性PET显像剂.     

The Bowman-Birk protease inhibitor enhances clonogenic cell survival of ionizing radiation-treated nucleotide excision repair-competent cells but not of xeroderma pigmentosum cells

Purpose : The radioprotective effect of the Bowman-Birk protease inhibitor (BBI) was previously shown to result from a TP53 dependent mechanism. Whether this effect involves specific DNA repair mechansims is now tested. Material and methods : Normal human fibroblasts were pre-treated with BBI before exposure to X-rays, UVB or to chemical agents (bleomycin, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cisplatin). These agents were chosen because of their ability to induce different spectra of DNA damage. The radiometric agent bleomycin primarily induces double-strand breaks (dsb), which are repaired by recombination; MNNG results in alkylated bases which are repaired by base excision repair (BER); cisplatin results in DNA-crosslinks which are repaired mainly by nucleotide excision repair (NER); and finally UVB generates thymine dimers and thymine-cytosine-6-4 products which are also repaired by NER. Cell survival was analysed by colony formation assay and DNA dsb by constant field gel electrophoresis. The combined effect of BBI and X-rays was also tested for XP-fibroblasts, which are defective in NER. Results : For normal human fibroblasts the radioprotective effect of BBI was clearly found by using a delayed plating procedure. The radioprotective effect was found to be unrelated to an altered induction or repair of radiation-induced DNA dsb. Pre-treatment with BBI did not affect cell killing after exposure to bleomycin or MNNG, but resulted in a significant protection of cells exposed to cisplatin or UVB. These results indicate that pre-treatment with BBI did not alter recombination repair or BER, but was able to modify NER. The latter finding was supported by the observation made for XP-cells, where pre-treatment with BBI failed to result in radioprotection after exposure to ionizing radiation. Conclusions : On the basis of these data it is proposed that the radioprotective effect of BBI is the result of an improved nucleotide excision repair mechanism.     

The Bowman-Birk protease inhibitor enhances clonogenic cell survival of ionizing radiation-treated nucleotide excision repair-competent cells but not of xeroderma pigmentosum cells

PURPOSE: The radioprotective effect of the Bowman-Birk protease inhibitor (BBI) was previously shown to result from a TP53 dependent mechanism. Whether this effect involves specific DNA repair mechanisms is now tested. MATERIAL AND METHODS: Normal human fibroblasts were pre-treated with BBI before exposure to X-rays, UVB or to chemical agents (bleomycin, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cisplatin). These agents were chosen because of their ability to induce different spectra of DNA damage. The radiometric agent bleomycin primarily induces double-strand breaks (dsb), which are repaired by recombination; MNNG results in alkylated bases which are repaired by base excision repair (BER); cisplatin results in DNA-crosslinks which are repaired mainly by nucleotide excision repair (NER); and finally UVB generates thymine dimers and thymine-cytosine-6-4 products which are also repaired by NER. Cell survival was analysed by colony formation assay and DNA dsb by constant field gel electrophoresis. The combined effect of BBI and X-rays was also tested for XP-fibroblasts, which are defective in NER. RESULTS: For normal human fibroblasts the radioprotective effect of BBI was clearly found by using a delayed plating procedure. The radioprotective effect was found to be unrelated to an altered induction or repair of radiation-induced DNA dsb. Pretreatment with BBI did not affect cell killing after exposure to bleomycin or MNNG, but resulted in a significant protection of cells exposed to cisplatin or UVB. These results indicate that pre-treatment with BBI did not alter recombination repair or BER, but was able to modify NER. The latter finding was supported by the observation made for XP-cells, where pretreatment with BBI failed to result in radioprotection after exposure to ionizing radiation. CONCLUSIONS: On the basis of these data it is proposed that the radioprotective effect of BBI is the result of an improved nucleotide excision repair mechanism.