Murce Erika, de Blois Erik, van den Berg Sophie, de Jong Marion, Seimbille Yann
Department of Radiology and Nuclear Medicine, University Medical Center Rotterdam, Erasmus MC, Rotterdam, The Netherlands.
Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
R Soc Open Sci. 2023 Mar 8;10(3):220950. doi: 10.1098/rsos.220950. eCollection 2023 Mar.
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.
靶向放射性核素治疗（TRT）是一种治疗不同类型癌症的有前景的策略。TRT依赖于一种靶向载体，用于将治疗性放射性核素特异性地递送至肿瘤部位。已经合成了几种靶向前列腺特异性膜抗原（PSMA）的低分子量配体，但其药代动力学性质仍需优化。在此，我们描述了具有可裂解连接子甘氨酸 - 酪氨酸 - 赖氨酸（GYK）和甲硫氨酸 - 缬氨酸 - 赖氨酸（MVK）的新缀合物的合成，以减少输送到肾脏的剂量。化合物通过固相肽合成（SPPS）合成，化学纯度大于95％。用In - 111和Lu - 177进行放射性标记，以验证这些化合物作为成像和治疗剂的潜在用途。两种核素的放射化学纯度均大于80％，但含甲硫氨酸的类似物观察到明显的辐射分解。迄今为止用GYK - PSMA缀合物获得的结果可能值得进一步的生物学研究。
