Liu Shuang, Harris Thomas D, Ellars Charles E, Edwards D Scott
Bristol-Myers Squibb Medical Imaging, 331 Treble Cove Road, North Billerica, Massachusetts 01862, USA.
Bioconjug Chem. 2003 Sep-Oct;14(5):1030-7. doi: 10.1021/bc020061h.
This study describes the discovery and development of an anaerobic formulation for the routine preparation of (90)Y and (177)Lu complexes ((90)Y-TA138 and (177)Lu-TA138) of a DOTA-conjugated nonpeptide vitronectin receptor antagonist (TA138: 3-sulfon-N-[[4,7,10-tris(carboxymethyl)1,4,7,10-tetraazacyclododec-1-yl]acetyl]-l-alanyl-N-[2-[4-[[[(1S)-1-carboxy-2[[[1,4-dihydro-7-[(1H-imidazol-2-ylamino]meth-yl]-1-methyl-4-oxo-3-quinolinyl]carbonyl]amino]ethyl]amino]-sulfonyl]-3,5-dimethylphenoxy]-1-oxobutyl]amino]ethyl]-3-sulfo-l-alaninamide). Since (90)Y-TA138 and (177)Lu-TA138 are very sensitive to radiolytic degradation, exclusion of oxygen is necessary during the radiolabeling. Using the anaerobic formulation, (90)Y-TA138 and (177)Lu-TA138 can be prepared in high yield and high specific activity. The anaerobic formulation described in this study is particularly useful for (90)Y- and (177)Lu-labeling of DOTA-conjugated small biomolecules, which are sensitive to the radiolytic degradation during radiolabeling.
本研究描述了一种用于常规制备DOTA共轭非肽玻连蛋白受体拮抗剂（TA138：3-磺基-N-[[4,7,10-三（羧甲基）-1,4,7,10-四氮杂环十二烷基]乙酰基]-L-丙氨酰基-N-[2-[4-[[[(1S)-1-羧基-2[[[1,4-二氢-7-[(1H-咪唑-2-基氨基]甲基]-1-甲基-4-氧代-3-喹啉基]羰基]氨基]乙基]氨基]-磺酰基]-3,5-二甲基苯氧基]-1-氧代丁基]氨基]乙基]-3-磺基-L-丙氨酰胺）的（90）Y和（177）Lu配合物（（90）Y-TA138和（177）Lu-TA138）的厌氧制剂的发现和开发。由于（90）Y-TA138和（177）Lu-TA138对辐射降解非常敏感，因此在放射性标记过程中必须排除氧气。使用该厌氧制剂，可以高产率和高比活度制备（90）Y-TA138和（177）Lu-TA138。本研究中描述的厌氧制剂对于DOTA共轭小生物分子的（90）Y和（177）Lu标记特别有用，这些小生物分子在放射性标记过程中对辐射降解敏感。
