In this work, we describe the complex formation and radiochemistry of the cyclen-based chelator DOTI-Me bearing four methylimidazole arms. Radiolabeling properties were evaluated for ^52gMn, ⁶⁴Cu, ⁶⁸Ga, ¹¹¹In, ¹⁶¹Tb, and ¹⁷⁷Lu, and DOTI-Me showed distinct differences to the structurally related H₄DOTA. While radiochemical conversions (RCCs) for ^52gMn and ¹¹¹In were comparable to those of H₄DOTA, DOTI-Me was not suited for ⁶⁸Ga. Conversely, quantitative RCCs were achieved for ⁶⁴Cu at ambient temperature, while elevated temperatures were required for complexation with H₄DOTA. For ¹⁶¹Tb and ¹⁷⁷Lu, good but not quantitative RCCs were obtained with DOTI-Me. With the exemption of ⁶⁸Ga³⁺, radiolabeled complexes showed high stability in ligand challenge experiments and in human serum. X-ray analysis of the nonradioactive complexes revealed the formation of 8-coordinate Mn²⁺ and In³⁺ DOTI-Me complexes. Cu²⁺ adopted a unique distorted square-pyramidal 2 + 3 with the neutral DOTI-Me ligand and a Jahn–Teller distorted 4 + 2 coordination geometry for the diprotonated H₂DOTI-Me²⁺ cation, respectively. For Zn²⁺, the complex with HDOTI-Me⁺ showed a distorted 4 + 3 pentagonal bipyramidal geometry. Summarizing, the ligand DOTI-Me may be an interesting alternative to H₄DOTA for ^52gMn, ⁶⁴Cu, ¹¹¹In, ¹⁶¹Tb, and ¹⁷⁷Lu, covering diagnostic as well as therapeutic radionuclides. Further studies of targeted radiopharmaceuticals based on the DOTI-Me scaffold in combination with the set of radiometals presented herein are thus warranted.

中文翻译：

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Cyclen 衍生的螯合剂 DOTI-Me 与 Mn2+、Cu2+、Zn2+、Ga3+、In3+、Tb3+ 和 Lu3+ 的放射化学和复合物形成


在这项工作中，我们描述了带有四个甲基咪唑臂的基于环素的螯合剂 DOTI-Me 的复合物形成和放射化学。评估了 ^52gMn、⁶⁴Cu、⁶⁸Ga、¹¹¹In、¹⁶¹Tb 和 ¹⁷⁷Lu 的放射性标记特性，DOTI-Me 与结构相关的 H₄DOTA 显示出明显差异。虽然 ^52gMn 和 ¹¹¹In 的放射化学转化率 （RCC） 与 H₄DOTA 相当，但 DOTI-Me 不适用于 ⁶⁸Ga。相反，在环境温度下，⁶⁴Cu 的定量 RCC 可实现，而与 H₄DOTA 络合需要高温。对于 ¹⁶¹Tb 和 ¹⁷⁷Lu，使用 DOTI-Me 获得良好但不定量的 RCC。在豁免 ⁶⁸Ga³⁺ 的情况下，放射性标记的复合物在配体攻击实验和人血清中表现出高稳定性。非放射性配合物的 X 射线分析揭示了 8 配位 Mn²⁺ 和 In³⁺ DOTI-Me 配合物的形成。Cu²⁺ 分别采用具有中性 DOTI-Me 配体的独特扭曲方形金字塔 2 + 3 和二质子化 H₂DOTI-Me²⁺ 阳离子的 Jahn-Teller 扭曲 4 + 2 配位几何。对于 Zn²⁺，与 HDOTI-Me⁺ 的复合物显示出扭曲的 4 + 3 五边形双锥几何形状。总而言之，配体 DOTI-Me 可能是 H₄DOTA 的有趣替代品，适用于 ^52gMn、⁶⁴Cu、¹¹¹In、¹⁶¹Tb 和 ¹⁷⁷Lu，涵盖诊断和治疗放射性核素。 因此，有必要进一步研究基于 DOTI-Me 支架的靶向放射性药物与本文提出的一组放射性金属相结合。