[^99mTc]Tc-DGA1, a Promising CCK₂R-Antagonist-Based Tracer for Tumor Diagnosis with Single-Photon Emission Computed Tomography

Abstract

Radiolabeled gastrin analogues have been proposed for theranostics of cholecystokinin subtype 2 receptor (CCK₂R)-positive cancer. Peptide radioligands based on other receptor antagonists have displayed superior pharmacokinetics and higher biosafety than agonists. Here, we present DGA1, a derivative of the nonpeptidic CCK₂R antagonist Z-360 carrying an acyclic tetraamine, for [^99mTc]Tc labeling. Preclinical comparison of [^99mTc]Tc-DGA1 with [^99mTc]Tc-DG2 (CCK₂R-agonist reference) was conducted in HEK293-CCK₂R/CCK_2i4svR cells and mice models, qualifying [^99mTc]Tc-DGA1 for further study in patients with CCK₂R-positive tumors and single-photon emission computed tomography/CT.