Nonradioactive Cell Assay for the Evaluation of Modular Prostate-Specific Membrane Antigen Targeting Ligands via Inductively Coupled Plasma Mass Spectrometry

J Med Chem. 2019 Dec 12;62(23):10912-10918. doi: 10.1021/acs.jmedchem.9b01606. Epub 2019 Nov 26.

Abstract

The development of novel prostate-specific membrane antigen (PSMA)-targeted radioactive theranostic agents is currently limited to facilities capable of working with high-energy radioisotopes. Even preselection of lead structures in vitro relies mostly on radioactive assays with PSMA(+) LNCaP and PSMA(-) PC-3 cells. Assays utilizing radioisotopes are time consuming, costly, and limit discovery to a small group of scientists with special facilities. Nonradioactive alternatives are therefore needed in the field. In this paper, we describe an inductively coupled plasma mass spectrometry (ICP-MS)-based method for the evaluation of PSMA-targeting ligands conjugated to DOTA-chelates of Europium. This method is based on LNCaP and PC-3 cells and has been validated with the well-established targeting ligand PSMA-617.

Publication types

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

MeSH terms

  • Antigens, Surface / chemistry*
  • Biological Assay
  • Cell Line, Tumor
  • Europium / chemistry*
  • Glutamate Carboxypeptidase II / chemistry*
  • Humans
  • Male
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / immunology*
  • Sensitivity and Specificity
  • Spectrophotometry, Atomic

Substances

  • Antigens, Surface
  • Europium
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II