[99mTc]Tc-DGA1, a Promising CCK2R-Antagonist-Based Tracer for Tumor Diagnosis with Single-Photon Emission Computed Tomography.
Aikaterini KaloudiPanagiotis KanellopoulosThorsten RadolfOleg G ChepurnyMaritina RouchotaGeorge LoudosFritz AndreaeGeorge G HolzBerthold Artur NockTheodosia MainaPublished in: Molecular pharmaceutics (2020)
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/CCK2i4svR cells and mice models, qualifying [99mTc]Tc-DGA1 for further study in patients with CCK2R-positive tumors and single-photon emission computed tomography/CT.
Keyphrases
- computed tomography
- positron emission tomography
- dual energy
- image quality
- magnetic resonance imaging
- contrast enhanced
- induced apoptosis
- stem cells
- insulin resistance
- cell therapy
- young adults
- molecular docking
- mesenchymal stem cells
- signaling pathway
- bone marrow
- skeletal muscle
- high fat diet induced
- binding protein
- molecular dynamics simulations
- clinical evaluation