Radiofluorination of a pre-formed gallium(III) aza-macrocyclic complex: towards next-generation positron emission tomography (PET) imaging agents.
Radiofluorination of a pre-formed gallium(III) aza-macrocyclic complex: towards next-generation positron emission tomography (PET) imaging agents.
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DOI：
10.1002/chem.201405812
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发表时间：
2015-03-16
期刊：
影响因子：
--
通讯作者：
Reid G
中科院分区：
文献类型：
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作者：
Bhalla R;Levason W;Luthra SK;McRobbie G;Sanderson G;Reid G
为了探索影响新型高效金属络合物正电子发射断层显像剂发展的因素，通过1-benzyl-1，4，7-triazacyclononane-4，7-dicarboxylic酸盐酸盐(H_2L-⋅)与Ga(NO_3)_3- _9-H_2O反应制备了扭曲的八面体配合物[GaCl(L)]Ga_2-⋅H_2O。本文报道了[GaCl(L)]⋅_2MeCN_2O的光谱和结晶学数据，以及[GaCl(L)] _2MeCN的晶体结构。通过Cl−/F−交换实现了该络合物的氟化，在室温下用KF在水中处理超过90 分钟，虽然反应在大约30 分钟内完成，如果加热到80 °C，以良好的产率得到[GAF(L)]⋅2 H2O。以GaF_3-⋅_3- -H_2O和Li_2L为原料，水热合成了该化合物，并用单晶X-射线分析、IR、1H和19F{1H} 谱和ESI+MS对其进行了表征。在pH为4的NaOAc水溶液中，用无载体的18F-⋅证明了预制的[GaCl(L)]- -H_2O在210 纳米摩尔尺度上发生了放射性氟化反应，加热到80 °C，30分钟后，18F-的掺杂率达到60-70 %。使用固相萃取柱可以很容易地纯化得到的放射性产品，放射化学纯度为98-99 %。在pH为 6的10 %乙醇/NaOAc溶液中，[Ga18F(L)]至少稳定90 分钟，但在pH约为7.5时，在磷酸盐缓冲盐水或人血清白蛋白中脱氟。在开发潜在的 新显像剂的背景下，讨论了13族金属离子和共配体给体在影响该体系的pH依赖性方面的微妙作用。
As part of a study to investigate the factors influencing the development of new, more effective metal-complex-based positron emission tomography (PET) imaging agents, the distorted octahedral complex, [GaCl(L)]⋅2 H2O has been prepared by reaction of 1-benzyl-1,4,7-triazacyclononane-4,7-dicarboxylic acid hydrochloride (H2L⋅HCl) with Ga(NO3)3⋅9 H2O, which is a convenient source of GaIII for reactions in water. Spectroscopic and crystallographic data for [GaCl(L)]⋅2 H2O are described, together with the crystal structure of [GaCl(L)]⋅MeCN. Fluorination of this complex by Cl−/F− exchange was achieved in high yield by treatment with KF in water at room temperature over 90 minutes, although the reaction was complete in approximately 30 minutes if heated to 80 °C, giving [GaF(L)]⋅2 H2O in good yield. The same complex was obtained by hydrothermal synthesis from GaF3⋅3 H2O and Li2L, and has been characterised by single-crystal X-ray analysis, IR, 1H and 19F{1H} NMR spectroscopy and ESI+ MS. Radiofluorination of the pre-formed [GaCl(L)]⋅2 H2O has been demonstrated on a 210 nanomolar scale in aqueous NaOAc at pH 4 by using carrier-free 18F−, leading to 60–70 % 18F-incorporation after heating to 80 °C for 30 minutes. The resulting radioproduct was purified easily by using a solid-phase extraction (SPE) cartridge, leading to 98–99 % radiochemical purity. The [Ga18F(L)] is stable for at least 90 minutes in 10 % EtOH/NaOAc solution at pH 6, but defluorinates over this time scale at pH of approximately 7.5 in phosphate buffered saline (PBS) or human serum albumin (HSA). The subtle role of the Group 13 metal ion and co-ligand donor set in influencing the pH dependence of this system is discussed in the context of developing potential new imaging agents for PET.