ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer’s disease with a bispecific,brain-penetrating fusion protein

作     者：Gillian Bonvicini Stina Syvänen Ken G.Andersson Merja Haaparanta-Solin Francisco López-Picón Dag Sehlin 

作者机构：Department of Public Health and Caring SciencesUppsala University75185 UppsalaSweden BioArctic AB11251 StockholmSweden Preclinical Imaging LaboratoryTurku PET CentreUniversity of Turku20520 TurkuFin-land MediCity Research LaboratoryUniversity of Turku20520 TurkuFinland. 

出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)

年 卷 期：2022年第11卷第1期

页      面：70-83页

核心收录：

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

基　　金：the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No.813528,the Swedish Research Council(2017-02413,2018-02715,2021-1083 and 2021-03524),the Swedish Innovation Agency(2019-00106) Alzheimerfonden,Hjärnfonden,Hedlunds stiftelse,Torsten Söderbergs stiftelse,Åhlenstiftelsen,Stiftelsen för gamla tjänarinnor,Stohnes stiftelse,Magnus Bergvalls stiftelse,Konug Gustaf V:s och Drottning Victorias frimuarestiftelse,Åke Wibergs stiftelse and Turku University Hospital.The funding organizations did not take part in designing the study,in collecting,analysing,or interpreting the data,or in writing the manuscript 

主　　题：ImmunoPET Transferrin receptor Alzheimer’s disease Amyloid-beta 

摘      要：Background:Hijacking the transferrin receptor(TfR)is an effective strategy to transport amyloid-beta(Aβ)immuno-positron emission tomography(immunoPET)ligands across the blood-brain barrier(BBB).Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβpathology in mouse models of Alzheimer’s disease(AD).This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET ***:Two affinity variants of the rat TfR antibody,OX26,were chemically conjugated to a F(ab′)2 fragment of the anti-Aβantibody,bapineuzumab(Bapi),to generate two bispecific fusion proteins:OX265-F(ab′)2-Bapi and OX2676-F(ab′)*** analyses were performed 4 h and 70 h post-injection of radioiodinated fusion proteins in wild-type(WT)rats.[124I]I-OX265-F(ab′)2-Bapi was administered to TgF344-AD and WT rats for in vivo PET *** vivo distribution of injected[124I]I-OX265-F(ab′)2-Bapi and Aβpathology were ***:More[125I]I-OX265-F(ab′)2-Bapi was taken up into the brain 4 h post-administration than[124I]I-OX2676-F(ab′)2-Bapi.[124I]I-OX265-F(ab′)2-Bapi PET visualized Aβpathology with significantly higher signals in the TgF344-AD rats than in the WT littermates without Aβ*** PET signals significantly correlated with Aβlevels in AD ***:Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB,such that the higher-affinity bispecific fusion protein crossed the BBB more ***,bispecific immunoPET imaging of brain Aβpathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats,suggesting that this immunoPET strategy has the potential to be translated to higher species.