[ 99m Tc]Tc-DGA1, a Promising CCK 2 R-Antagonist-Based Tracer for Tumor Diagnosis with SPECT.

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 [Tc-99m]Tc labeling. Preclinical comparison of [Tc-99m]Tc-DGA1 with [Tc-99m]Tc-DG2 (CCK2R-agonist reference) was conducted in HEK293-CCK2R/CCK2i4svR cells and mice models, qualifying [Tc-99m]Tc-DGA1 for further study in patients with CCK2R-positive tumors and single-photon emission computed tomography/CT.