Two bifunctional chelating agents used in 99Tcm labeling: NHS-MAG3 and HYNIC

兰晓莉　

摘　要：99Tcm在标记蛋白、核酸、多肽和抗体时,常采用双功能螯合剂作为偶联剂的间接标记法,以避免直接标记所带来的损伤.研究表明,近年来常用的两种螯合剂NHS-MAG3及HYNIC合成路线清晰,偶联及标记方法成熟,标记率、放化纯及比活度较高,为核素分子显像提供了必要的基础条件和广阔的临床应用前景.
关键词：双功能螯合剂;巯基乙酰三甘氨酰-N-羟基丁二酰亚胺酯;肼基尼古酰胺;锝;同位素标记
分类号：R817.9　文献标识码：A
文章编号：1001-098X(2005)01-0015-04
 
基金项目：国家自然科学基金项目(30271439);高等学校博士点基金项目(20030487013)
作者单位：兰晓莉（430022,武汉,华中科技大学同济医学院附属协和医院核医学科）　

参考文献：

[1]Winnard P Jr, Chang F, Rusckowski M, et al. Preparation and use of NHS-MAG3 for technetium-99m labeling of DNA[J]. Nucl Med Biol, 1997, 24(5): 425-432.
[2]齐传民,郭雪峰,张华北,等.新N3S型类肽配体的合成及其小鼠体内的生物分布研究[J].药学学报,2002,37(6):428-432.
[3]高再荣,张凯军,张永学.Survivin反义寡核苷酸的99mTc标记及在肝癌细胞中的表达[J].放射学实践,2004,19(1):50-52.
[4]Hnatowich DJ, Qu T, Chang F, et al. Labeling peptide with technetium-99m using a bifunctional chelator of a N-hydroxysuccinimide ester of mercaptoacetyltrigycine[J]. J Nucl Med, 1998,39( 1 ): 56-64.
[5]Gano L, Patry'cio L, Marques E, et al. Human polyclonal immunoglob ulin labelled with technetium-99m via NHS-MAG3: A comparison of radiochemical behavior and biological efficacy with other labelling methods[J]. Nucl Med Biol,1998, 25(4): 395-403.
[6]Lei K, Rusckowski M, Chang F, et al. Technetium-99m antibodies labeled with MAG3 and SHNH: an in vitro and animal in vivo comparison[J]. Nucl Med Biol, 1996, 23 (7): 917-922.
[7]Wang Y, Chang F, Zhang Y, et al. Pretargeting with amplification using polymeric peptide nucleic acid[J]. Bioconjug Chem, 2001, 12 (5): 807-816.
[8]Liu G, Zhang S, He J, et al. Improving the labeling of S-acetyl NHS- MAG (3)-conjugated morpholino oligomers [J]. Bioconjug Chem,2002, 13(4): 893-897.
[9]Abrams M J, Juweid M, Abrams M J, et al. Technetium-99m-human polyelonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats[J]. J Nucl Med, 1990, 31 (12): 2022-2028.
[10]Edwards DS, Liu S. 99mTc-labelling of hydrazinonicotinamide (HYNIC) modified highly potent small molecules: problems and solutions[J]. Transition Met Chem, 1997, 22(4): 425-426.
[11]Ono M, Arano Y, Mukai T, et al. Control of radioactivity pharmacokinetics of 99mTc-HYNIC-Labeled polypeptides derivatized with ternary ligand complexes[J]. Bioconjugate Chem, 2002, 13 (3):491-501.
[12]Verbeke K, Kieffer D, Vanderheyden JL, et al. Optimization of the preparation of 99mTc-labeled Hynic-derivatized Annexin V for human use[J]. Nucl Med Biol, 2003, 30(7): 771-778.
[13]Rennen HJJM, van Eerd J E, Oyen W J G, et al. Effects of coligand variation on the in vivo characteristics of Tc-99m-labeled interleukin-8 in detection of infection[J]. Bioconjugate Chem, 2002,13(2): 370-377.
[14]Su ZF, He J, Rusckowski M, et al. In vitro cell studies of technetium-99m labeled RGD-HYNIC peptide, a comparison of tricine and EDDA as co-ligands[J]. Nucl Med Biol, 2003, 30(2): 141-149.
[15]Zhang YM, Liu CB, Liu N, et al. Electrostatic binding with tat and other cationic peptides increases cell accumulation of 99mTc-antisense DNAs without entrapment[J]. Mol Imaging Biol, 2003, 5(4): 240-247.
[16]Welling M M, Visentinb R, Feitsmaa HIJ, et al. Infection detection in mice using 99mTc-labeled HYNIC and N2S2 chelate conjugated to the antimicrobial peptide UBI 29-41[J]. Nucl Med Biol,2004, 31(4): 503-509.
[17]Rennen HJJM, Boerman OC, Koenders E B, et al. Labeling proteins with Tc-99m via Hydrazinonicotinamide (HYNIC): optimization of the conjugation reaction[J]. Nucl Med Biol, 2000, 27(6): 599-604.
[18]He J, Liu C, Vanderheyden JL, et al. Radiolabelling morpholinos with 188Re tricarbonyl provides improved in vitro and in vivo stability to re-oxidation[J]. Nucl Med Commun,2004, 25(7):731-736.
[19]Liu S, Edwards DS, Ziegler MC, et al. 99mTc-labeling of a hydrazinonicotinamide-conjugated vitronectin receptor antagonist useful for imaging tumors[J]. Bioconjugate Chem, 2001, 12(4): 624-629.
[20]Rennen HJJM, Makarewicz J, Oyen WJG, et al. The effect of molecular weight on nonspecific accumulation of 99mTc-labeled proteins in inflammatory foci[J]. Nucl Med Biol, 2001, 28(4):401-408.