Radiochemistry of cyclen-derived chelators comprising five-membered azaheterocyclic arms with 212Pb2+, 213Bi3+, and 225Ac3+

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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 212 Pb, 213 Bi, and 225 Ac 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 212 Pb at room temperature, comparable to those of the current gold standard for Pb complexation, TCMC, while it was not well suited for 213 Bi. Contrarily, DOTI-Me exhibited quantitative radiochemical conversions for 213 Bi at pH 5.5 and room temperature, outperforming the metal chelator macropa, but was not able to quantitatively complex 212 Pb under any conditions investigated. Of note, both novel chelators were not able to bind 225 Ac. In preliminary experiments, we could also show that a functionalized DOTI-Me derivative is capable of complexing 213 Bi selectively from 225 Ac solutions. This feature may allow the preparation of 213 Bi-labeled radiotracers directly from 225 Ac solutions without the need for an 225 Ac/ 213 Bi generator. However, more detailed studies are needed to fully explore this potential application. Altogether, our results support the future development of 212 Pb-labeled radiopharmaceuticals using bifunctional derivatives of DOTThia as well as of 213 Bi-labeled radiotracers based on the DOTI-Me scaffold.