Effect of chelators on the pharmacokinetics of (99m)Tc-labeled imaging agents for the prostate-specific membrane antigen (PSMA)

J Med Chem. 2013 Aug 8;56(15):6108-21. doi: 10.1021/jm400823w. Epub 2013 Jul 22.


Technetium-99m, the most commonly used radionuclide in nuclear medicine, can be attached to biologically important molecules through a variety of chelating agents, the choice of which depends upon the imaging application. The prostate-specific membrane antigen (PSMA) is increasingly recognized as an important target for imaging and therapy of prostate cancer (PCa). Three different (99m)Tc-labeling methods were employed to investigate the effect of the chelator on the biodistribution and PCa tumor uptake profiles of 12 new urea-based PSMA-targeted radiotracers. This series includes hydrophilic ligands for radiolabeling with the [(99m)Tc(CO)3](+) core (L8-L10), traditional NxSy-based chelating agents with varying charge and polarity for the (99m)Tc-oxo core (L11-L18), and a (99m)Tc-organohydrazine-labeled radioligand (L19). (99m)Tc(I)-Tricarbonyl-labeled [(99m)Tc]L8 produced the highest PSMA+ PC3 PIP to PSMA- PC3 flu tumor ratios and demonstrated the lowest retention in normal tissues including kidney after 2 h. These results suggest that choice of chelator is an important pharmacokinetic consideration in the development of (99m)Tc-labeled radiopharmaceuticals targeting PSMA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Surface / metabolism*
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacokinetics*
  • Glutamate Carboxypeptidase II / metabolism*
  • Hydrazines / chemistry
  • Hydrazines / pharmacokinetics*
  • Hydrophobic and Hydrophilic Interactions
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Multimodal Imaging
  • Neoplasm Transplantation
  • Positron-Emission Tomography
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics*
  • Structure-Activity Relationship
  • Technetium*
  • Tissue Distribution
  • Tomography, X-Ray Computed
  • Urea / analogs & derivatives*
  • Urea / chemistry
  • Urea / pharmacokinetics*


  • Antigens, Surface
  • Chelating Agents
  • Hydrazines
  • Radiopharmaceuticals
  • Technetium
  • Urea
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II