Positron Emission Tomography Imaging of Neurotensin Receptor-Positive Tumors with ⁶⁸Ga-Labeled Antagonists: The Chelate Makes the Difference Again

Neurotensin receptor 1 (NTS1) is involved in the development and progression of numerous cancers, which makes it an interesting target for diagnostic therapeutic agents. A small molecule NTS1 antagonist, named [177Lu]Lu-IPN01087, currently evaluated phase I/II clinical trials targeted therapy neurotensin receptor-positive cancers. In this study, we synthesized seven compounds based on structure antagonists, bearing different chelating agents, radiolabeled them with gallium-68 PET imaging. These were vitro vivo mice a HT-29 xenograft. The compound [68Ga]Ga-bisNODAGA-16 showed promising biodistribution profile mainly signal tumor (4.917 ± 0.776%ID/g, 2 h post-injection). Its rapid clearance from healthy tissues led to high tumor-to-organ ratios, resulting highly contrasted images. results confirmed subcutaneous xenografts AsPC-1 cells, model NTS1-positive human pancreatic adenocarcinoma.