Advances in research on radiopharmaceuticals targeting NTSR1

Neurotensin Receptor 1 (NTSR1) is a Class A G protein-coupled receptor(GPCRs) that exhibits high affinity for neurotensin. Overexpression of NTSR1 in various cancers makes it a promising target for tumor-specific imaging and therapy. Currently, radioligands such as the small-molecule antagonist 3BP-227 and the peptide agonist [⁶⁸Ga]DOTA-NT-20.3 have entered clinical trials. However, NTSR1-targeted radiopharmaceuticals still face challenges including suboptimal tumor-to-background ratios, high renal accumulation, and the lack of validated theranostic pairs for patient stratification. Studies have shown that pharmacokinetic modifiers such as hydrophilic linkers and albumin-binding moieties can significantly modulate ligand bioavailability as well as imaging and therapeutic efficacy. This review systematically elaborates recent advances in the development of compounds targeting NTSR1, focusing on the molecular structures and biological activities of radiolabeled peptide and non-peptide derivatives. It emphasizes their applications in tumor imaging diagnosis and targeted radiotherapy. The article aims to provide a reference for drug development based on NTSR1 ligands.