Kimura Hiroyuki, Mori Daisuke, Harada Naoya, Ono Masahiro, Ohmomo Yoshiro, Kajimoto Tetsuya, Kawashima Hidekazu, Saji Hideo
Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Chem Pharm Bull (Tokyo). 2012;60(1):79-85. doi: 10.1248/cpb.60.79.
(99m)Tc-tricarbonyl [(99m)Tc(CO)(3)] complexes have been conventionally synthesized by heating (99m)Tc(CO)(3)(H(2)O)(3) and a tridentate chelating ligand under atmospheric pressure; however, this method is poor in terms of chemical yield and reproducibility. Moreover, since the half-life of (99m)Tc is very short (6 h), the development of facile and rapid methods of synthesizing (99m)Tc-labeled compounds, which could be used as radioactive tracers for single photon emission computed tomography (SPECT), is required. Thus, we initiated a study on the application of a microwave reaction to the synthesis of (99m)Tc(CO)(3)-2-picolylamine monoacetic acid (PAMA) [(99m)Tc(CO)(3)-PAMA] complexes on the basis of the fact that synthesis of metal complexes proceeds rapidly by microwave irradiation owing to an efficient exothermic phenomenon and heat conduction effect. Formation of by-products could be markedly suppressed by comparison with that in conventional methods. In the present study, rhenium (Re), an element belonging to the same group in the periodic table as technetium (Tc), and which also forms bipyramidal complexes, was first used to investigate the synthetic reaction because no stable isotopes exist for Tc. As a result, when water was used as the solvent under the irradiation of microwaves within 1 min, the Re(CO)(3)-PAMA complex could be directly synthesized from ethyl ester of PAMA (PAMAEE) and [Re(CO)(3)(H(2)O)(3)]Br in one step and with a high yield (94%). Finally, the (99m)Tc(CO)(3)-PAMA complex was successfully synthesized at a high radiochemical yield (>99%) within 1 min of reaction using (99m)Tc instead of Re under the same conditions.
（99m）锝-三羰基[（99m）Tc（CO）₃]配合物传统上是通过在大气压下加热[（99m）Tc（CO）₃（H₂O）₃]⁺和三齿螯合配体来合成的；然而，这种方法在化学产率和可重复性方面较差。此外，由于（99m）Tc的半衰期非常短（6小时），因此需要开发简便快速的合成（99m）Tc标记化合物的方法，这些化合物可用作单光子发射计算机断层扫描（SPECT）的放射性示踪剂。因此，基于金属配合物的合成由于高效的放热现象和热传导效应在微波辐射下迅速进行这一事实，我们开始研究微波反应在合成（99m）Tc（CO）₃-2-吡啶甲胺单乙酸（PAMA）[（99m）Tc（CO）₃-PAMA]配合物中的应用。与传统方法相比，副产物的形成可以明显受到抑制。在本研究中，铼（Re）是与锝（Tc）在元素周期表中属于同一族且也形成双锥配合物的元素，由于Tc不存在稳定同位素，因此首先用它来研究合成反应。结果，当在1分钟内微波辐射下以水为溶剂时，Re（CO）₃-PAMA配合物可以从PAMA的乙酯（PAMAEE）和[Re（CO）₃（H₂O）₃]Br一步直接合成，产率很高（94%）。最后，在相同条件下使用（99m）Tc代替Re，在1分钟的反应时间内以高放射化学产率（>99%）成功合成了（99m）Tc（CO）₃-PAMA配合物。
