A Novel Radiotracer for NTSR1-Targeted PET Imaging of Tumor: Preclinical and First-in-Human Studies

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Oncology

Background:

• Neurotensin receptor 1 (NTSR1) is overexpressed in several cancers, presenting a target for diagnostic and therapeutic agents.
• Current NTSR1-targeting peptides suffer from rapid clearance and low tumor accumulation, hindering clinical use.

Purpose of the Study:

• To develop and evaluate a novel positron emission tomography (PET) tracer for NTSR1-expressing tumors.
• To improve upon existing NTSR1-targeting peptides by enhancing their pharmacokinetic properties.

Main Methods:

• Conjugation of the DOTA-NT-20.3 peptide with an albumin-binding moiety (4-(p-iodophenyl)butyric acid [IPBA]).
• Radiolabeling with Gallium-68 ([68Ga]) to form [68Ga]Ga-DOTA-NT-20.3-IPBA.
• In vitro stability, radiochemical yield, purity, affinity, and specificity assessments.
• In vivo biodistribution and PET/CT imaging in tumor-bearing models and patients.

Main Results:

• The novel tracer [68Ga]Ga-DOTA-NT-20.3-IPBA demonstrated high in vitro stability (>95%) and radiochemical yield (>95%).
• The tracer exhibited high affinity and specificity for NTSR1.
• Clinical PET/CT imaging showed significant accumulation in lung adenocarcinoma with a tumor-to-lung ratio of 7.89 ± 0.76 at 60 min postinjection.

Conclusions:

• [68Ga]Ga-DOTA-NT-20.3-IPBA is a promising PET tracer for imaging NTSR1-positive tumors, particularly lung adenocarcinoma.
• The albumin-binding moiety improved tracer properties, suggesting potential for theranostic applications.