Peptide-Based PET Imaging Agent [ ⁶⁸ Ga]Ga-DOTA-NT-20.3-Ibu for Noninvasive Evaluation of Tumor Neurotensin Receptor 1 Expression

High neurotensin receptor 1 (NTSR1) expression is strongly associated with progression and poor prognosis across multiple malignancies. We designed an NTSR1-targeted peptide-based PET probe conjugated with the albumin-binding moiety ibuprofen, designated [⁶⁸Ga]Ga-DOTA-NT-20.3-Ibu, which was synthesized with high radiochemical yield and purity, exhibited sufficient <i>in vitro</i> stability, and demonstrated favorable serum albumin-binding capacity. Cell binding/uptake assays, animal-based PET imaging, and biodistribution studies confirmed the radiotracer's high affinity and specificity for NTSR1. In human participants, [⁶⁸Ga]Ga-DOTA-NT-20.3-Ibu was safe and primarily excreted via the urinary system. Bone marrow uptake was detectable with SUVmean of 4.11 ± 1.59 and 4.99 ± 1.82 at 60 and 120 min postinjection, respectively. Mild uptake was observed in the blood pool, liver, spleen, pancreas, stomach, and bowel, while other tissues showed minimal uptake. Importantly, lung tumor uptake of [⁶⁸Ga]Ga-DOTA-NT-20.3-Ibu correlated with NTSR1 expression levels. Collectively, [⁶⁸Ga]Ga-DOTA-NT-20.3-Ibu PET enables accurate, noninvasive assessment of tumor NTSR1 expression, facilitating NTSR1-targeted cancer treatment and prognosis monitoring.