Synthesis and radiolabelling of PSMA-targeted derivatives containing GYK/MVK cleavable linkers

Targeted radionuclide therapy (TRT) is a promising strategy to treat different types of cancer. TRT relies on a targeting vector used to deliver a therapeutic radionuclide specifically to the tumour site. Several low molecular weight ligands targeting the prostate-specific membrane antigen (PSMA) ha...

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Bibliographic Details
Published in:	Royal Society open science 2023-03, Vol.10 (3), p.220950-220950
Main Authors:	Murce, Erika, de Blois, Erik, van den Berg, Sophie, de Jong, Marion, Seimbille, Yann
Format:	Article
Language:	eng
Subjects:	albumin binder Chemistry cleavable linkers prostate cancer prostate-specific membrane antigen solid phase peptide synthesis targeted radionuclide therapy
Online Access:	Get full text
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Summary:	Targeted radionuclide therapy (TRT) is a promising strategy to treat different types of cancer. TRT relies on a targeting vector used to deliver a therapeutic radionuclide specifically to the tumour site. Several low molecular weight ligands targeting the prostate-specific membrane antigen (PSMA) have been synthesized, but their pharmacokinetic properties still need to be optimized. Hereby, we describe the synthesis of new conjugates, featuring the cleavable linkers Gly-Tyr-Lys (GYK) and Met-Val-Lys (MVK), to reduce the dose delivered to the kidneys. Compounds were synthesized by solid-phase peptide synthesis (SPPS) and obtained in greater than 95% chemical purity. Radiolabelling was performed with both In-111 and Lu-177 to validate potential use of the compounds as both imaging and therapeutic agents. Radiochemical purity greater than 80% was obtained for both nuclides, but significant radiolysis was observed for the methionine-containing analogue. The results obtained thus far with the GYK-PSMA conjugate could warrant further biological investigations.
ISSN:	2054-5703 2054-5703