(44)Sc-PSMA-617 for radiotheragnostics in tandem with (177)Lu-PSMA-617-preclinical investigations in comparison with (68)Ga-PSMA-11 and (68)Ga-PSMA-617.

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 ((68)Ga) and radionuclide therapy ((177)Lu) in the clinics.

In this study, PSMA-617 was labeled with cyclotron-produced (44)Sc (T 1/2 = 4.04 h) and investigated preclinically for its use as a diagnostic match to (177)Lu-PSMA-617.

(44)Sc was produced at the research cyclotron at PSI by irradiation of enriched (44)Ca targets, followed by chromatographic separation. (44)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. (44)Sc-PSMA-617 was evaluated in vitro and compared to the (177)Lu- and (68)Ga-labeled match, as well as (68)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 (177)Lu- and (68)Ga-labeled PSMA-617. Moreover, (44)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. (44)Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of (44)Sc-PSMA-617 resembled that of (177)Lu-PSMA-617 most closely, while the (68)Ga-labeled ligands, in particular (68)Ga-PSMA-11, showed different distribution kinetics. (44)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.

The in vitro characteristics and in vivo kinetics of (44)Sc-PSMA-617 were more similar to (177)Lu-PSMA-617 than to (68)Ga-PSMA-617 and 68Ga-PSMA-11. Due to the almost four-fold longer half-life of (44)Sc as compared to (68)Ga, a centralized production of (44)Sc-PSMA-617 and transport to satellite PET centers would be feasible. These features make (44)Sc-PSMA-617 particularly appealing for clinical application.

EJNMMI research. 2017 Jan 19 [Epub]

Christoph A Umbricht, Martina Benešová, Raffaella M Schmid, Andreas Türler, Roger Schibli, Nicholas P van der Meulen, Cristina Müller

Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, 5232, Villigen-PSI, Switzerland., Laboratory of Radiochemistry, Paul Scherrer Institut, Villigen-PSI, Switzerland., Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, 5232, Villigen-PSI, Switzerland. .