Laboratory of Physical Chemistry, Showa Pharmaceutical University, Japan; Laboratory of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Japan.
Laboratory of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Japan.
Nucl Med Biol. 2020 Jul-Aug;86-87:30-36. doi: 10.1016/j.nucmedbio.2020.05.004. Epub 2020 May 16.
Tc-labeled hexavalent probes can be readily synthesized by the coordination of six equivalent isocyanide ligands towards Tc, and alkyl isocyanide ligands have been extensively used for preparing such probes. However, high ligand concentration (>1 mM) is generally required due to their insufficient coordination ability to Tc.
In this study, we revealed that aryl isocyanide ligands, which have greater π-accepting ability compared with alkyl ones, provided Tc-labeled hexavalent probes in high radiochemical yields (>95%) even at low ligand concentration (50 μM). We applied this finding to the synthesis of a Tc-labeled hexavalent RGD probe, targeting integrin αβ. This Tc-labeled probe was prepared in a 5 min reaction at ligand concentration of 50 μM, and exhibited high tumor localization in vivo without post-labeling purification.
The present findings indicate that aryl isocyanide ligands would be a useful precursor to a variety of Tc-labeled hexavalent targeting probes for molecular imaging of saturable systems.
Aryl isocyanide is a better precursor than alkyl isocyanide for preparing Tc-labeled hexavalent targeting probe.
This work provides a straightforward method to prepare molecular imaging agents of high target uptake, which would facilitate nuclear medicine imaging in clinical settings.
Tc 标记的六价探针可以通过 Tc 与六个等效异氰化物配体的配位来轻易合成，并且烷基异氰化物配体已被广泛用于制备此类探针。然而，由于其与 Tc 的配位能力不足，通常需要高浓度的配体（>1mM）。
在这项研究中，我们发现与烷基异氰化物相比，具有更大π-接受能力的芳基异氰化物配体即使在低浓度（50μM）下也能以高放射化学产率（>95%）提供 Tc 标记的六价探针。我们将这一发现应用于整合素 αβ 靶向的 Tc 标记六价 RGD 探针的合成。该 Tc 标记探针在 50μM 配体浓度下 5 分钟的反应中即可制备，并且在体内具有高肿瘤定位，无需进行标记后纯化。
本研究结果表明，芳基异氰化物配体将成为各种用于饱和系统分子成像的 Tc 标记六价靶向探针的有用前体。
与烷基异氰化物相比，芳基异氰化物是制备 Tc 标记六价靶向探针的更好前体。
这项工作提供了一种制备高靶摄取分子成像剂的简便方法，这将有助于核医学成像在临床环境中的应用。
