Development of a ¹⁷⁷Lu-labeled radiopeptide for targeted CXCR4 positive tumor therapy

The peptide sequence as an antagonist of chemokine receptor 4 (CXCR4) was evaluated as a radio-therapeutic agent. The peptide derivative was coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled by lutetium-177. Labeling yield, lipophilicity, and plasma stability of ¹⁷⁷Lu-labeled ligand were determined. In vitro tests such as cellular uptake and internalization in the C6 glioma cell line were analyzed. Tissue biodistribution was investigated in rats bearing C6 glioma tumors. Radioligand showed >90 % radiochemical purity and specific activity of 5.60 GBq/μmol. ¹⁷⁷Lu-DOTA-CXCR4 ligand showed binding to C6 tumor cells. The ex vivo distribution profile of ¹⁷⁷Lu-labeled ligand showed that, except for the kidneys, all non-target organs exhibited extremely low uptake of the ¹⁷⁷Lu-labeled ligand. The data confirm acceptable CXCR4-targeting by the prepared radioligand and establish it as a candidate for further optimization for clinical use.