Abstract: Gastrin releasing peptide receptor (GRPR) is overexpressed in various tumors, and these GRPR-positive tumors have successfully and widely been targeted with GRPR antagonists. To achieve a good therapeutic effectiveness and less radioactive dosage administration, high cellular internalization is required. The cellular internalization of agonists is better than that of antagonists, but the severe side effects of agonists restrict their applications. In this study, we hypothesized that introducing membrane penetrating oligo-phenylene-ethynylene (OPE) to GRPR antagonist RM26 could increase the cellular internalization of antagonists. Therefore, two multi-functional compounds NOTA-OPE-1-RM26 and NOTA-OPE-2-RM26 were synthesized and labelled with 177Lu with high efficiency. The ¹⁷⁷Lu labelled compounds ¹⁷⁷Lu-NOTA-OPEs-RM26 were stable in saline, dulbecco’s modified eagle medium (DMEM) and newborn bovine serum. The in vitro experimental results indicated that the introduction of OPE-1 slightly increased the cellular internalization of the radiolabelled compounds while OPE-2 significantly increased the cellular internalization. In addition, the introduction of OPEs did not change the specific binding ability of RM26. The investigations indicated that introducing the OPE to increase the internalization was feasible.