68Ga/DOTA- and 64Cu/NOTA-Phthalocyanine Conjugates as Fluorescent/PET Bimodal Imaging Probes
68Ga/DOTA- and 64Cu/NOTA-Phthalocyanine Conjugates as Fluorescent/PET Bimodal Imaging Probes
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DOI：
10.1021/bc400257u
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发表时间：
2013-09-01
影响因子：
4.7
通讯作者：
Guerin, Brigitte
中科院分区：
文献类型：
--
作者：
Ranyuk, Elena;Lebel, Rejean;Guerin, Brigitte
本文报道了一系列新型双峰探针的合成和表征，它们分别以水溶性磺化锌酞菁为荧光成像单元，Ga-68/1，4，7，10-四氮杂环十二烷-N，N‘n’，N‘-四乙酸或铜-/1，4，7-三氮杂环-1，4，7-三乙酸为显像剂。这两个部分通过不同长度的脂肪链连接在一起，以调节两亲性。用Ga-68(t(1/2)=68min)和铜-(t(1/2)=12.7h)标记DOTA或NOTA-ZnPc偶联物，在100℃下标记15min，所有偶联物的效率均为90%。体外血浆稳定性分析表明，铜-/NOTa-ZnPc结合物具有较高的稳定性，在24 h内保持完好，而Ga-68/DOTA-ZnPc结合物具有较高的稳定性，在3 h内释放出高达7%的游离Ga-68。基于体外血浆稳定性结果，我们对两个铜-标记的衍生物进行了研究，这使得我们能够选择一个候选者进行初步的体内实验。荧光和PET成像证实了这些新型偶联物作为双峰探针的潜力。
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 Ga-68/1,4,7,10-tetraazocyclododecane-N,N'N '',N'''-tetraacetic acid (DOTA) or Cu-64/1,4,7-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 Ga-68 (t(1/2) = 68 min) and Cu-64 (t(1/2) = 12.7 h) was performed at 100 degrees C for 15 min with >90% efficiency for all conjugates. In vitro plasma stability assays demonstrated high stability of the Cu-64/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and reasonably high stability of the Ga-68/DOTA-ZnPc conjugate, which released up to 7% of free Ga-68 over a 3 h period. Based on in vitro plasma stability results, we performed studies on two Cu-64-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.