Development of Novel Gastrin-Releasing Peptide Receptor-Targeted Radioligand with Albumin Binder to Improve Accumulation in Tumor

Gastrin-releasing peptide receptor (GRPR) is a promising target for cancer radiotheranostics combining nuclear imaging with targeted radionuclide therapy. Improving the accumulation of radioligands in tumors by introducing an albumin binder (ALB) is useful to promote the efficacy of radiotheranostics. In this study, we designed and synthesized a novel GRPR-targeted radioligand [¹¹¹In]In-AMTG-DA1 containing an ALB moiety to improve tumor accumulation. [¹¹¹In]In-AMTG-DA1 showed marked binding ability to albumin, high affinity for GRPR, and high-level stability <i>in vitro</i>. In biodistribution studies, the tumor accumulation of [¹¹¹In]In-AMTG-DA1 was much higher than that of the control ligand without an ALB moiety. The introduction of ALB increased the tumor area under the curve (AUC) value of [¹¹¹In]In-AMTG-DA1 by 3.5 times. In a single-photon emission computed tomography (SPECT) study, [¹¹¹In]In-AMTG-DA1 visualized a GRPR-expressing tumor clearly at 24 h postinjection. Our findings suggest the favorable pharmacokinetics of [¹¹¹In]In-AMTG-DA1 as a GRPR-targeted radioligand exhibiting a high-level accumulation in tumors.