68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer

J Med Chem. 2010 Jul 22;53(14):5333-41. doi: 10.1021/jm100623e.


Gallium-68 is a generator-produced radionuclide for positron emission tomography (PET) that is being increasingly used for radiolabeling of tumor-targeting peptides. Compounds [(68)Ga]3 and [(68)Ga]6 are high-affinity urea-based inhibitors of the prostate-specific membrane antigen (PSMA) that were synthesized in decay-uncorrected yields ranging from 60% to 70% and radiochemical purities of more than 99%. Compound [(68)Ga]3 demonstrated 3.78 +/- 0.90% injected dose per gram of tissue (%ID/g) within PSMA+ PIP tumor at 30 min postinjection, while [(68)Ga]6 showed a 2 h PSMA+ PIP tumor uptake value of 3.29 +/- 0.77 %ID/g. Target (PSMA+ PIP) to nontarget (PSMA- flu) ratios were 4.6 and 18.3, respectively, at those time points. Both compounds delineated tumor clearly by small animal PET. The urea series of imaging agents for PSMA can be radiolabeled with (68)Ga, a cyclotron-free isotope useful for clinical PET studies, with maintenance of target specificity.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Gallium Radioisotopes
  • Humans
  • Isotope Labeling
  • Male
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / pharmacology
  • Positron-Emission Tomography
  • Prostate-Specific Antigen / antagonists & inhibitors*
  • Prostatic Neoplasms / diagnostic imaging*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / pharmacology
  • Tissue Distribution
  • Transplantation, Heterologous


  • 2-(3-(1-carboxy-5-(7-(5-carboxy-5-(3-phenyl-2-(3-phenyl-2-(2-(4,7,10-triscarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetylamino)propionylamino)propionylamino)pentylcarbamoyl)heptanoylamino)pentyl)ureido)pentanedioic acid gallium(III)
  • 2-(3-(5-(7-(1-benzyloxycarbonyl-5-(2-(4,7,10-triscarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetylamino)pentylcarbamoyl)heptanoylamino)-1-carboxypentyl)ureido)pentanedioic acid gallium(III)
  • Gallium Radioisotopes
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Prostate-Specific Antigen