A PET probe targeting polyamine transport system for precise tumor diagnosis and therapy  

作　　者：Ming Zhou Xiaoqin Yin Bei Chen Shuo Hu Wenhu Zhou 

机构地区：[1]Department of Nuclear Medicine,Xiangya Hospital,Central South University,Changsha 410008,China [2]Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,China [3]Key Laboratory of Biological Nanotechnology of National Health Commission,Changsha 410008,China [4]National Clinical Research Center for Geriatric Disorders(Xiangya),Changsha 410008,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第3期146-159,共14页亚洲药物制剂科学（英文）

基　　金：supported by the Science and Technology Innovation Team Talent Project of Hunan Province(No.2021RC4056);the clinical research foundation of the National Clinical Research Center for Geriatric Diseases(XIANGYA)(No.2020LNJJ01);the Natural Science Foundation of Hunan Province in China(No.2021JJ20084);the Science and Technology Innovation Program of Hunan Province(No.2021RC3020)。

摘　　要：Polyamine metabolism dysregulation is a hallmark of many cancers,offering a promising avenue for early tumor theranostics.This study presents the development of a nuclear probe derived from spermidine(SPM)for dual-purpose tumor PET imaging and internal radiation therapy.The probe,radiolabeled with either[68Ga]Ga for diagnostic applications or[177Lu]Lu for therapeutic use,was synthesized with exceptional purity,stability,and specific activity.Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells,showcasing outstanding tumor localization and target-to-non-target ratio.Mechanistic investigations employing polyamines,non-labeled precursor,and polyamine transport system(PTS)inhibitor,consistently affirmed the probe?s targetability through recognition of the PTS.Notably,while previous reports indicated PTS upregulation in various tumor types for targeted therapy,this study observed no positive signals,highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis.Furthermore,when labeled with[177Lu],the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival.Investigations into biodistribution,excretion,and biosafety in healthy humans laid a robust foundation for clinical translation.This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics,offering promising prospects for clinical implementation.

关 键 词：PET imaging Polyamine metabolism SPERMINE RADIOPHARMACEUTICAL MELANOMA 

分 类 号：O657[理学—分析化学] R730[理学—化学]