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.