Zhai Chuangyan, Summer Dominik, Rangger Christine, Haas Hubertus, Haubner Roland, Decristoforo Clemens
Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria; Department of Nuclear Medicine, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
J Labelled Comp Radiopharm. 2015 May 15;58(5):209-14. doi: 10.1002/jlcr.3286. Epub 2015 Apr 15.
Fusarinine C (FSC), a siderophore-based chelator coupled with the model peptide c(RGDfK) (FSC(succ-RGD)3), revealed excellent targeting properties in vivo using positron emission tomography (PET). Here, we report the details of radiolabeling conditions and specific activity as well as selectivity for (68)Ga. (68)Ga labeling of FSC(succ-RGD)3 was optimized regarding peptide concentration, pH, temperature, reaction time, and buffer system. Specific activity (SA) of [(68)Ga]FSC(succ-RGD)3 was compared with (68)Ga-1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid RGD ([(68)Ga]NODAGA-RGD). Stability was evaluated in 1000-fold ethylenediaminetetraacetic acid (EDTA) solution (pH 7) and phosphate-buffered saline (PBS). Metal competition tests (Fe, Cu, Zn, Al, and Ni) were carried out using [(68)Ga]-triacetylfusarinine C. High radiochemical yield was achieved within 5 min at room temperature, in particular allowing labeling with (68)Ga up to pH 8 with excellent stability in 1000-fold EDTA solution and PBS. The 10-fold to 20-fold lower concentrations of FSC(succ-RGD)3 led to the same radiochemical yield compared with [(68)Ga]NODAGA-RGD with SA up to 1.8 TBq/µmol. Metal competition tests showed high selective binding of (68)Ga to FSC. FSC is a multivalent siderophore-based bifunctional chelator allowing fast and highly selective labeling with (68)Ga in a wide pH range and results in stable complexes with high SA. Thus it is exceptionally well suited for the development of new (68)Ga-tracers for in vivo molecular imaging with PET.
基于铁载体的螯合剂富萨里宁C（FSC）与模型肽c(RGDfK)（FSC(succ-RGD)3）偶联，在正电子发射断层扫描（PET）的体内实验中显示出优异的靶向特性。在此，我们报告了放射性标记条件、比活度以及对68Ga的选择性的详细情况。针对肽浓度、pH值、温度、反应时间和缓冲体系，对FSC(succ-RGD)3的68Ga标记进行了优化。将[(68)Ga]FSC(succ-RGD)3的比活度（SA）与68Ga-1,4,7-三氮杂环壬烷-1-戊二酸-4,7-乙酸RGD（[(68)Ga]NODAGA-RGD）进行了比较。在1000倍乙二胺四乙酸（EDTA）溶液（pH 7）和磷酸盐缓冲盐水（PBS）中评估了稳定性。使用[(68)Ga]-三乙酰富萨里宁C进行了金属竞争试验（铁、铜、锌、铝和镍）。在室温下5分钟内实现了高放射化学产率，特别是在pH值高达8时允许用68Ga标记，在1000倍EDTA溶液和PBS中具有优异的稳定性。与[(68)Ga]NODAGA-RGD相比，FSC(succ-RGD)3浓度低10至20倍时导致相同的放射化学产率，SA高达1.8 TBq/µmol。金属竞争试验表明68Ga对FSC具有高选择性结合。FSC是一种基于多价铁载体的双功能螯合剂，能够在很宽的pH范围内快速且高度选择性地用68Ga标记，并形成具有高SA的稳定络合物。因此，它非常适合用于开发新型68Ga示踪剂，用于PET体内分子成像。
