Radiochemistry and Complex Formation of the Cyclen-Derived Chelator DOTI-Me with Mn 2+ , Cu 2+ , Zn 2+ , Ga 3+ , In 3+ , Tb 3+ , and Lu 3 .

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 ^52g Mn, ⁶⁴ Cu, ⁶⁸ Ga, ¹¹¹ In, ¹⁶¹ Tb, and ¹⁷⁷ Lu, and DOTI-Me showed distinct differences to the structurally related H ₄ DOTA. While radiochemical conversions (RCCs) for ^52g Mn and ¹¹¹ In were comparable to those of H ₄ DOTA, DOTI-Me was not suited for ⁶⁸ Ga. Conversely, quantitative RCCs were achieved for ⁶⁴ Cu at ambient temperature, while elevated temperatures were required for complexation with H ₄ DOTA. For ¹⁶¹ Tb and ¹⁷⁷ Lu, good but not quantitative RCCs were obtained with DOTI-Me. With the exemption of ⁶⁸ Ga ³⁺ , 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 Mn ²⁺ and In ³⁺ DOTI-Me complexes. Cu ²⁺ 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 H ₂ DOTI-Me ²⁺ cation, respectively. For Zn ²⁺ , the complex with HDOTI-Me ⁺ showed a distorted 4 + 3 pentagonal bipyramidal geometry. Summarizing, the ligand DOTI-Me may be an interesting alternative to H ₄ DOTA for ^52g Mn, ⁶⁴ Cu, ¹¹¹ In, ¹⁶¹ Tb, and ¹⁷⁷ Lu, 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.