Narrative review discusses NTS1-targeted molecular probes for malignancies with noted translation challenges.

Neurotensin receptor 1 (NTS1) is a high-affinity G protein-coupled receptor (GPCR) for the endogenous peptide neurotensin (NT). NTS1 is overexpressed across multiple malignancies and is an important target for precision theranostics. In recent years, NTS1-targeted molecular probes have advanced considerably, improving the sensitivity and specificity of molecular imaging, including fluorescence imaging, positron emission tomography (PET), single-photon emission computed tomography (SPECT), and multimodal PET/fluorescence imaging, while also showing promise for response assessment and therapeutic decision-making. In parallel, theranostic strategies that integrate molecular imaging with targeted therapy enable a closed-loop workflow for patient stratification, individualized treatment, and response monitoring. In this review, we summarize recent advances in NTS1-targeted molecular probes, with particular emphasis on their clinical applications in tumor molecular imaging, radioligand therapy, and integrated diagnostic and therapeutic management. We integrate evidence from preclinical models and early human studies and outline the main challenges that currently limit their clinical translation. Overall, this review aims to provide a useful reference for the continued development of NTS1-targeted molecular probes in precision oncology.