Preclinical Investigations to Explore the Difference between the Diastereomers [Lu]Lu-SibuDAB and [Lu]Lu-RibuDAB toward Prostate Cancer Therapy.

[Lu]Lu-Ibu-DAB-PSMA, a radioligand modified with ibuprofen as the albumin binder, showed higher accumulation in PSMA-positive tumors of mice than the clinically used [Lu]Lu-PSMA-617 but lower retention in non-targeted tissues than previously developed albumin-binding PSMA radioligands. The aim of this study was to investigate whether the stereochemistry of the incorporated ibuprofen affects the radioligand's and properties and to select the more favorable radioligand for further development. For this purpose, SibuDAB and RibuDAB containing ()- and ()-ibuprofen, respectively, were synthesized and labeled with lutetium-177.