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

Abstract

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.

• Authors: Sangeeta Ray Banerjee, Mrudula Pullambhatla, Youngjoo Byun, Sridhar Nimmagadda, Gilbert Green, James J Fox, Andrew Horti, Ronnie C Mease, Martin G Pomper
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 53 Issue 14 Pg. 5333-41 (Jul 22 2010) ISSN: 1520-4804 [Electronic] United States
• PMID: 20568777 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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