Neurotensin-Based Radioligands for NTS₁R-Targeted Cancer Theranostics: Background, Current Status and Future Trends

Background/Objectives: The neurotensin subtype-1 receptor (NTS₁R) is overexpressed in a number of human tumors, representing a valid biomolecular target for neurotensin-based radionuclide carriers. The latter are designed to deposit diagnostic-therapeutic radionuclides specifically on cancer lesions. This review summarizes research efforts toward the development, preclinical evaluation and first clinical outcomes of neurotensin-based radioligands in the diagnosis and therapy-radiotheranostics-of NTS₁R-positive cancer. Methods: The preclinical and few clinical studies related to NTS₁R-targeted radiotheranostics are discussed. The crucial issue of in vivo metabolic stability is highlighted. Results: Much effort has been dedicated to the development of effective NTS₁R-directed radioligands for cancer theranostics, most of which are peptide-based. However, clinical success has been sub-optimal thus far, partly as a result of their fast degradation in the biological milieu. Conclusions: The administration of key protease inhibitor regimens, the introduction of branched or otherwise stabilized analogs and the advent of non-peptidic NTS₁R-antagonists are some of the new promising approaches towards achieving clinical breakthroughs in the battle against NTS₁R-expressing cancer.