Mundwiler Stefan, Candreia Lukas, Häfliger Pascal, Ortner Kirstin, Alberto Roger
Department of Inorganic Chemistry, University of Zürich, CH-8057 Zürich, Switzerland.
Bioconjug Chem. 2004 Jan-Feb;15(1):195-202. doi: 10.1021/bc034171f.
A novel method for the preparation of no-carrier-added (nca) complexes [99mTc(CO)3L] (L = diethylenetriamine or picolylamine-N-acetic acid) is described. The ligands were covalently bound to a solid support of organic polymers via formation of a tertiary amine from the chelating unit. This C-N bond to the solid phase is selectively cleaved during the formation of the technetium complexes by intramolecular nucleophilic attack of a remaining hydroxy ligand to the alpha-carbon. The complex [99mTc(CO)3L] is released into solution while uncomplexed ligand and uncleaved complex remain solid-phase bound. High specific activity technetium complexes can then be isolated by simple filtration. Cleavage yield depends on temperature, pH, and ligand. Up to 50% release from the solid phase could be achieved under optimized conditions. Corresponding to the 99mTc concentration, free ligand is present in concentrations lower than 10(-7) M. If a targeting vector is conjugated to these ligands, no-carrier-added radiopharmaceuticals can be prepared in that way.
描述了一种制备无载体添加（nca）配合物[99mTc(CO)3L]（L = 二乙烯三胺或吡啶甲胺-N-乙酸）的新方法。通过螯合单元形成叔胺，使配体与有机聚合物的固体载体共价结合。在锝配合物形成过程中，剩余羟基配体对α-碳进行分子内亲核攻击，从而选择性地切断与固相的C-N键。配合物[99mTc(CO)3L]释放到溶液中，而未络合的配体和未切断的配合物仍与固相结合。然后通过简单过滤即可分离出高比活度的锝配合物。切断产率取决于温度、pH值和配体。在优化条件下，固相释放率可达50%。与99mTc浓度相对应，游离配体的浓度低于10^(-7) M。如果将靶向载体与这些配体偶联，就可以用这种方法制备无载体添加的放射性药物。
