Synthesis of Novel, Dual-Targeting 68Ga-NODAGA-LacN-E[c(RGDfK)]2 Glycopeptide as a PET Imaging Agent for Cancer Diagnosis

Radiolabeled peptides possessing an Arg-Gly-Asp (RGD) motif are widely used radiopharmaceuticals for PET imaging of tumor angiogenesis due to their high affinity and selectivity to alpha(v)beta(3) integrin. This receptor is overexpressed in tumor and tumor endothelial cells in the case of numerous cancer cell lines, therefore, it is an excellent biomarker for cancer diagnosis. The galectin-3 protein is also highly expressed in tumor cells and N-acetyllactosamine is a well-established ligand of this receptor. We have developed a synthetic method to prepare a lactosamine-containing radiotracer, namely Ga-68-NODAGA-LacN-E[c(RGDfK)](2), for cancer diagnosis. First, a lactosamine derivative with azido-propyl aglycone was synthetized. Then, NODAGA-NHS was attached to the amino group of this lactosamine derivative. The obtained compound was conjugated to an E[c(RGDfK)](2) peptide with a strain-promoted click reaction. We have accomplished the radiolabeling of the synthetized NODAGA-LacN-E[c(RGDfK)](2) precursor with a positron-emitting Ga-68 isotope (radiochemical yield of >95%). The purification of the labeled compound with solid-phase extraction resulted in a radiochemical purity of >99%. Subsequently, the octanol-water partition coefficient (log P) of the labeled complex was determined to be -2.58. In addition, the in vitro stability of Ga-68-NODAGA-LacN-E[c(RGDfK)](2) was investigated and it was found that it was stable under the examined conditions.

Automated summary

A novel radiotracer for cancer diagnosis containing lactosamine was successfully synthesized, showing high affinity and stability. The compound was labeled with a Ga-68 isotope with high radiochemical purity. This radiopharmaceutical has potential applications in tumor imaging in the future.