Molecular pharmaceutics
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Molecular pharmaceutics · Mar 2020
Development of 18F-Fluoroglycosylated PSMA-Ligands with Improved Renal Clearance Behavior.
The prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is highly expressed in the malignant human prostate epithelium. Therefore, PSMA has emerged as a very attractive target for developing radiopharmaceuticals for the diagnosis, e.g., by positron emission tomography (PET) imaging, and radiotherapy of prostate cancer. The aim of this study was to develop 18F-labeled PSMA ligands bearing different 18F-glycosyl moieties to study the effect on the in vivo clearance behavior of radiotracers in addition to their tumor binding ability. ⋯ The regional kidney distribution pattern of the tracers in the kidneys revealed that 68Ga-PSMA-11 and 2-[18F]FGlc-PSMA([18F]7) mainly accumulated in the cortex of the kidneys, whereas 6-[18F]FGlc-PSMA([18F]8) showed a 10-fold lower kidney uptake with accumulation in the inner medulla or pelvis of the kidneys. Overall, the developed 6-fluoroglucosyl derivative [18F]8, with its considerably low kidney uptake and fast clearance, demonstrated high uptake in PSMA-positive tumors in vivo. This candidate could, therefore, be valuable for translation into the clinic.