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

Mol Pharm. 2020 Aug 3;17(8):3116-3128. doi: 10.1021/acs.molpharmaceut.0c00605. Epub 2020 Jul 7.

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/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.

Keywords: CCK2 receptor; CCK2R antagonist; [99mTc]Tc radiotracer; molecular imaging; tumor single-photon emission computed tomography imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodiazepinones / metabolism*
  • Benzodiazepinones / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cholecystokinin / antagonists & inhibitors*
  • Gastrins / metabolism
  • HEK293 Cells
  • Humans
  • Isotope Labeling / methods
  • Male
  • Mice
  • Neoplasms / diagnosis*
  • Neoplasms / metabolism*
  • Peptide Fragments / antagonists & inhibitors*
  • Peptides / metabolism*
  • Radiopharmaceuticals / metabolism*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods

Substances

  • Benzodiazepinones
  • Gastrins
  • Peptide Fragments
  • Peptides
  • Radiopharmaceuticals
  • Z-360
  • cholecystokinin 9
  • Cholecystokinin