We have reported that the chelator-based clickable radiotheranostic platform, ADIBO-DOTADG-ALB (ADA), has favorable properties as a radiotheranostic platform for low-molecular-weight ligands. In this study, we evaluated the applicability of ADA to moderate-molecular-weight ligands to expand the utility of the ADA platform. As a moderate-molecular-weight ligand, we selected exendin-4, a peptide-based agonist to glucagon-like peptide-1 receptor (GLP-1R). An exendin-4-incorporated ADA derivative, exendin-4-Cys40-triazole-DOTADG-ALB (EtDA), was radiolabeled with 111In by the conjugation of exendin-4-Cys40 azide to [111In]In-ADA. The click ligation of exendin-4-Cys40 azide to [111In]In-ADA was quantitatively completed in 10 min under ambient conditions. In the in vitro cell-binding assay and albumin-binding assay, [111In]In-EtDA showed strong binding to both a GLP-1R-expressing cell and albumin. In the biodistribution assay, [111In]In-EtDA showed markedly protracted tumor uptake, which was significantly decreased by the coinjection of exendin-4-Cys40. The single photon emission computed tomography (SPECT) image of [111In]In-EtDA visualized the tumor clearly. These results indicated the utility of [111In]In-EtDA as a radiotheranostic agent, suggesting the applicability of the ADA platform to moderate-molecular-weight ligands.
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