⁶⁴Cu-labeled inhibitors of prostate-specific membrane antigen for PET imaging of prostate cancer

J Med Chem. 2014 Mar 27;57(6):2657-69. doi: 10.1021/jm401921j. Epub 2014 Mar 7.


Prostate-specific membrane antigen (PSMA) is a well-recognized target for identification and therapy of a variety of cancers. Here we report five (64)Cu-labeled inhibitors of PSMA, [(64)Cu]3-7, which are based on the lysine-glutamate urea scaffold and utilize a variety of macrocyclic chelators, namely NOTA(3), PCTA(4), Oxo-DO3A(5), CB-TE2A(6), and DOTA(7), in an effort to determine which provides the most suitable pharmacokinetics for in vivo PET imaging. [(64)Cu]3-7 were prepared in high radiochemical yield (60-90%) and purity (>95%). Positron emission tomography (PET) imaging studies of [(64)Cu]3-7 revealed specific accumulation in PSMA-expressing xenografts (PSMA+ PC3 PIP) relative to isogenic control tumor (PSMA- PC3 flu) and background tissue. The favorable kinetics and high image contrast provided by CB-TE2A chelated [(64)Cu]6 suggest it as the most promising among the candidates tested. That could be due to the higher stability of [(64)Cu]CB-TE2A as compared with [(64)Cu]NOTA, [(64)Cu]PCTA, [(64)Cu]Oxo-DO3A, and [(64)Cu]DOTA chelates in vivo.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry
  • Chromatography, High Pressure Liquid
  • Copper / chemistry
  • Copper Radioisotopes
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Image Processing, Computer-Assisted
  • Indicators and Reagents
  • Isotope Labeling / methods
  • Male
  • Mice
  • Neoplasm Transplantation
  • Positron-Emission Tomography
  • Prostate-Specific Antigen / antagonists & inhibitors*
  • Prostatic Neoplasms / diagnostic imaging*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Spectrophotometry, Ultraviolet
  • Tissue Distribution
  • Tomography, X-Ray Computed
  • Whole-Body Counting


  • Chelating Agents
  • Copper Radioisotopes
  • Indicators and Reagents
  • Radiopharmaceuticals
  • Copper
  • Glutamate Carboxypeptidase II
  • Prostate-Specific Antigen