Radiochemistry\nand Complex Formation of the Cyclen-Derived\nChelator DOTI-Me with Mn<sup>2+</sup>, Cu<sup>2+</sup>, Zn<sup>2+</sup>, Ga<sup>3+</sup>, In<sup>3+</sup>, Tb<sup>3+</su

In\nthis work, we describe the complex formation and radiochemistry\nof the cyclen-based chelator DOTI-Me bearing four methylimidazole\narms. Radiolabeling properties were evaluated for <sup>52g</sup>Mn, <sup>64</sup>Cu, <sup>68</sup>Ga, <sup>111</sup>In, <sup>161</sup>Tb,\nand <sup>177</sup>Lu, and DOTI-Me showed distinct differences to the\nstructurally related H<sub>4</sub>DOTA. While radiochemical conversions\n(RCCs) for <sup>52g</sup>Mn and <sup>111</sup>In were comparable to\nthose of H<sub>4</sub>DOTA, DOTI-Me was not suited for <sup>68</sup>Ga. Conversely, quantitative RCCs were achieved for <sup>64</sup>Cu at ambient temperature, while elevated temperatures were required\nfor complexation with H<sub>4</sub>DOTA. For <sup>161</sup>Tb and <sup>177</sup>Lu, good but not quantitative RCCs were obtained with DOTI-Me.\nWith the exemption of <sup>68</sup>Ga<sup>3+</sup>, radiolabeled complexes\nshowed high stability in ligand challenge experiments and in human\nserum. X-ray analysis of the nonradioactive complexes revealed the\nformation of 8-coordinate Mn<sup>2+</sup> and In<sup>3+</sup> DOTI-Me\ncomplexes. Cu<sup>2+</sup> adopted a unique distorted square-pyramidal\n2 + 3 with the neutral DOTI-Me ligand and a Jahn–Teller distorted\n4 + 2 coordination geometry for the diprotonated H<sub>2</sub>DOTI-Me<sup>2+</sup> cation, respectively. For Zn<sup>2+</sup>, the complex with\nHDOTI-Me<sup>+</sup> showed a distorted 4 + 3 pentagonal bipyramidal\ngeometry. Summarizing, the ligand DOTI-Me may be an interesting alternative\nto H<sub>4</sub>DOTA for <sup>52g</sup>Mn, <sup>64</sup>Cu, <sup>111</sup>In, <sup>161</sup>Tb, and <sup>177</sup>Lu, covering diagnostic as\nwell as therapeutic radionuclides. Further studies of targeted radiopharmaceuticals\nbased on the DOTI-Me scaffold in combination with the set of radiometals\npresented herein are thus warranted.