Radiochemistry of cyclen-derived chelators comprising five-membered azaheterocyclic arms with ²¹²Pb²⁺, ²¹³Bi³⁺, and...

In this work, we introduce the cyclen-based metal chelator DOTThia comprising four methylthiazole arms for metal complexation. Together with the recently described congener DOTI-Me bearing four methylimidazole arms, the radiochemistry of these two compounds with ²¹²Pb, ²¹³Bi, and ²²⁵Ac was investigated thoroughly. Radiolabeling experiments were performed at various pH values and temperatures to determine the optimal conditions for quantitative radiochemical conversions. Experiments revealed excellent complexation properties of DOTThia for ²¹²Pb at room temperature, comparable to those of the current gold standard for Pb complexation, TCMC, while it was not well suited for ²¹³Bi. Contrarily, DOTI-Me exhibited quantitative radiochemical conversions for ²¹³Bi at pH 5.5 and room temperature, outperforming the metal chelator macropa, but was not able to quantitatively complex ²¹²Pb under any conditions investigated. Of note, both novel chelators were not able to bind ²²⁵Ac. In preliminary experiments, we could also show that a functionalized DOTI-Me derivative is capable of complexing ²¹³Bi selectively from ²²⁵Ac solutions. This feature may allow the preparation of ²¹³Bi-labeled radiotracers directly from ²²⁵Ac solutions without the need for an ²²⁵Ac/²¹³Bi generator. However, more detailed studies are needed to fully explore this potential application. Altogether, our results support the future development of ²¹²Pb-labeled radiopharmaceuticals using bifunctional derivatives of DOTThia as well as of ²¹³Bi-labeled radiotracers based on the DOTI-Me scaffold.