Controlled Axial Coordination: Solid-Phase Synthesis and Purification of Metallo-Radiopharmaceuticals
Controlled Axial Coordination: Solid-Phase Synthesis and Purification of Metallo-Radiopharmaceuticals
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DOI：
10.1002/anie.200801936
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Holland, Jason P.
中科院分区：
文献类型：
--
作者：
Betts, Helen M.;Barnard, Peter J.;Holland, Jason P.
固载试剂在提高放射性诊断试剂的合成效率、纯度、方便性和安全性方面显示出巨大的潜力。正电子发射断层扫描（PET）成像剂[18 F]-2-氟-2-脱氧-d-葡萄糖的制备最近已被证明使用固体结合的底物，其在与[18 F]-氟离子反应时从固体支持物上选择性裂解。[1]虽然这种共价方法适用于氟离子的亲核取代化学，但其对金属核素的效用有限，迄今为止唯一的例子是将99 mTc与连接到树脂[2，3]和金表面的前配体结合使用。[4]因此，常规的固相合成受到对具有供体基团的前配体的要求的限制，所述供体基团可以共价连接到固体载体上，并且在与所需金属离子配位时从固体载体上裂解。在本文中，我们报告了一种基于ZnII底物与4-（二甲氨基）吡啶（DMAP）官能化聚苯乙烯树脂的选择性轴向配位的固相合成新策略[5]，并将其用于制备和纯化已知和潜在的64 Cu和99 mTc放射性药物。该策略适用于广泛的金属放射性核素，并且适合于在核医学中受到青睐的大环配体系统，因为它们具有高的体内稳定性。
Solid-supported reagents show great potential for improving the synthesis of radiodiagnostic agents, in terms of radiochemical yield and purity, as well as convenience and safety. The preparation of the positron emission tomography (PET) imaging agent [18F]-2-fluoro-2-deoxy-d-glucose has recently been demonstrated using a solid-bound substrate which is selectively cleaved from the solid support upon reaction with [18F]-fluoride ions.[1] Whilst this covalent approach is appropriate for the nucleophilic substitution chemistry of fluoride ions, its utility with metallonuclides is limited and the only examples to date have used 99mTc in conjunction with proligands attached to resins [2, 3] and gold surfaces.[4] Conventional solid-phase synthesis is therefore limited by the requirement for proligands possessing a donor group which can both be covalently attached to the solid support and cleaved from it upon coordination to the desired metal ion. Herein, we report a novel strategy for solid-phase synthesis based on selective axial coordination of ZnII substrates to 4-(dimethylamino) pyridine (DMAP)-functionalized polystyrene resin [5] and exemplify its use in the preparation and purification of known and potential 64Cu and 99mTc radiopharmaceuticals. This strategy is applicable to a wide range of metallic radionuclides and is suitable for the macrocyclic ligand systems that are favored in nuclear medicine because of their high in vivo stability.