Centre d'imagerie moléculaire de Sherbrooke (CIMS), †Departments of Nuclear Medicine and Radiobiology and §Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke ; 3001 12th Avenue North, Sherbrooke, Québec, Canada J1H 5N4.
Bioconjug Chem. 2013 Sep 18;24(9):1624-33. doi: 10.1021/bc400257u. Epub 2013 Aug 26.
In this paper, we describe the synthesis and characterization of a series of new bimodal probes combining water-soluble sulfonated zinc phthalocyanine (ZnPc) as a fluorescence imaging unit and either (68)Ga/1,4,7,10-tetraazocyclododecane-N,N'N″,N'″-tetraacetic acid (DOTA) or (64)Cu/1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for PET imaging. The two moieties were linked through aliphatic chains of different lengths to modulate amphiphilicity. Labeling of DOTA- or NOTA-ZnPc conjugates with (68)Ga (t1/2 = 68 min) and (64)Cu (t1/2 = 12.7 h) was performed at 100 °C for 15 min with >90% efficiency for all conjugates. In vitro plasma stability assays demonstrated high stability of the (64)Cu/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and reasonably high stability of the (68)Ga/DOTA-ZnPc conjugate, which released up to 7% of free (68)Ga over a 3 h period. Based on in vitro plasma stability results, we performed biodistribution studies on two (64)Cu-labeled derivatives, which allowed us to select a single candidate for preliminary in vivo experiments. Fluorescence and PET imaging confirmed the potential of these novel conjugates to act as bimodal probes.
在本文中，我们描述了一系列新的双模态探针的合成与表征，这些探针将水溶性磺化锌酞菁（ZnPc）作为荧光成像单元，与（68）Ga/1,4,7,10-四氮杂环十二烷-N,N'N″,N'″-四乙酸（DOTA）或（64）Cu/1,4,7-三氮杂环壬烷-1,4,7-三乙酸（NOTA）通过连接不同长度的脂肪链进行连接，以调节两亲性。DOTA-或 NOTA-ZnPc 缀合物与（68）Ga（t1/2 = 68 min）和（64）Cu（t1/2 = 12.7 h）的标记在 100°C 下进行 15 分钟，所有缀合物的标记效率均>90%。体外血浆稳定性研究表明，（64）Cu/NOTA-ZnPc 缀合物具有很高的稳定性，在 24 小时内保持完整，而（68）Ga/DOTA-ZnPc 缀合物具有相当高的稳定性，在 3 小时内释放的游离（68）Ga 不超过 7%。基于体外血浆稳定性研究，我们对两种（64）Cu 标记的衍生物进行了生物分布研究，从中选择了一个候选物进行初步的体内实验。荧光和 PET 成像证实了这些新型缀合物作为双模态探针的潜力。
