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EJNMMI Res. 2017 Dec;7(1):9. doi: 10.1186/s13550-017-0257-4. Epub 2017 Jan 19.

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

Author information

1
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, 5232, Villigen-PSI, Switzerland.
2
Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
3
Laboratory of Radiochemistry, Paul Scherrer Institut, Villigen-PSI, Switzerland.
4
Department of Chemistry and Biochemistry University of Bern, Bern, Switzerland.
5
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, 5232, Villigen-PSI, Switzerland. cristina.mueller@psi.ch.
6
Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland. cristina.mueller@psi.ch.

Abstract

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 (68Ga) and radionuclide therapy (177Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced 44Sc (T 1/2 = 4.04 h) and investigated preclinically for its use as a diagnostic match to 177Lu-PSMA-617.

RESULTS:

44Sc was produced at the research cyclotron at PSI by irradiation of enriched 44Ca targets, followed by chromatographic separation. 44Sc-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. 44Sc-PSMA-617 was evaluated in vitro and compared to the 177Lu- and 68Ga-labeled match, as well as 68Ga-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 177Lu- and 68Ga-labeled PSMA-617. Moreover, 44Sc-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. 44Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of 44Sc-PSMA-617 resembled that of 177Lu-PSMA-617 most closely, while the 68Ga-labeled ligands, in particular 68Ga-PSMA-11, showed different distribution kinetics. 44Sc-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 44Sc-PSMA-617 were more similar to 177Lu-PSMA-617 than to 68Ga-PSMA-617 and 68Ga-PSMA-11. Due to the almost four-fold longer half-life of 44Sc as compared to 68Ga, a centralized production of 44Sc-PSMA-617 and transport to satellite PET centers would be feasible. These features make 44Sc-PSMA-617 particularly appealing for clinical application.

KEYWORDS:

177Lu; 44Sc; 68Ga; Cyclotron; PET imaging; PSMA; Prostate cancer; Theragnostics

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