Search

Background: The targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane- N, N′, N′′, N′′′-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging (Ga) and radionuclide therapy (Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced Sc ( T = 4.04 h) and investigated preclinically for its use as a diagnostic match to Lu-PSMA-617. Results: Sc was produced at the research cyclotron at PSI by irradiation of enriched Ca targets, followed by chromatographic separation. Sc-PSMA-617 was prepared under standard labeling conditions at elevated temperature resulting in a radiochemical purity of >97% at a specific activity of up to 10 MBq/nmol. Sc-PSMA-617 was evaluated in vitro and compared to the Lu- and Ga-labeled match, as well as Ga-PSMA-11 using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu prostate cancer cells. In these experiments it revealed similar in vitro properties to that of Lu- and Ga-labeled PSMA-617. Moreover, Sc-PSMA-617 bound specifically to PSMA-expressing PC-3 PIP tumor cells, while unspecific binding to PC-3 flu cells was not observed. The radioligands were investigated with regard to their in vivo properties in PC-3 PIP/flu tumor-bearing mice. Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of Sc-PSMA-617 resembled that of Lu-PSMA-617 most closely, while the Ga-labeled ligands, in particular Ga-PSMA-11, showed different distribution kinetics. Sc-PSMA-617 enabled distinct visualization of PC-3 PIP tumor xenografts shortly after injection, with increasing tumor-to-background contrast over time while unspecific uptake in the PC-3 flu tumors was not observed. Conclusions: The in vitro characteristics and in vivo kinetics of Sc-PSMA-617 were more similar to Lu-PSMA-617 than to Ga-PSMA-617 and 68Ga-PSMA-11. Due to the almost four-fold longer half-life of Sc as compared to Ga, a centralized production of Sc-PSMA-617 and transport to satellite PET centers would be feasible. These features make Sc-PSMA-617 particularly appealing for clinical application. [ABSTRACT FROM AUTHOR]

Background: Terbium has attracted the attention of researchers and physicians due to the existence of four medically interesting radionuclides, potentially useful for SPECT and PET imaging, as well as for α- and β-radionuclide therapy. The aim of this study was to produce Tb ( T = 17.5 h, E = 1140 keV) and evaluate it in a preclinical setting in order to demonstrate its potential for PET imaging. For this purpose, DOTANOC was used for targeting the somatostatin receptor in AR42J tumor-bearing mice. Methods: Tb was produced by proton-induced spallation of tantalum targets, followed by an online isotope separation process at ISOLDE/CERN. After separation of Tb using cation exchange chromatography, it was directly employed for radiolabeling of DOTANOC. PET/CT scans were performed with AR42J tumor-bearing mice at different time points after injection of Tb-DOTANOC which was applied at variable molar peptide amounts. Lu-DOTANOC was prepared and used in biodistribution and SPECT/CT imaging studies for comparison with the PET results. Results: After purification, Tb was obtained at activities up to ~600 MBq. Radiolabeling of DOTANOC was achieved at a specific activity of 10 MBq/nmol with a radiochemical purity >98 %. The PET/CT scans of mice allowed visualization of AR42J tumor xenografts and the kidneys, in which the radiopeptide was accumulated. After injection of large peptide amounts, the tumor uptake was reduced as compared to the result after injection of small peptide amounts. PET images of mice, which received Tb-DOTANOC at small peptide amounts, revealed the best tumor-to-kidney ratios. The data obtained with Lu-DOTANOC in biodistribution and SPECT/CT imaging studies confirmed the Tb-based PET results. Conclusions: Production of 30-fold higher quantities of Tb as compared to the previously performed pilot study was feasible. This allowed, for the first time, labeling of a peptide at a reasonable specific activity and subsequent application for in vivo PET imaging. As a β-particle-emitting radiolanthanide, Tb would be of distinct value for clinical application, as it may allow exact prediction of the tissue distribution of therapeutic radiolanthanides. [ABSTRACT FROM AUTHOR]