A New, Second Generation Trithiol Bifunctional Chelate for 72,77As: Trithiol(b)-(Ser)2-RM2.
A New, Second Generation Trithiol Bifunctional Chelate for 72,77As: Trithiol(b)-(Ser)2-RM2.
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72,77As 的新型第二代三硫醇双功能螯合物：三硫醇(b)-(Ser)2-RM2。
DOI：
10.1021/acs.bioconjchem.0c00658
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发表时间：
2021
影响因子：
4.7
通讯作者：
Jurisson,SilviaS
中科院分区：
文献类型：
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作者：
NajafiKhosroshahi,Firouzeh;Feng,Yutian;Ma,Li;Manring,Simon;Rold,TammyL;Gallazzi,FabioA;Kelley,StevenP;Embree,MaryF;Hennkens,HeatherM;Hoffman,TimothyJ;Jurisson,SilviaS
三硫醇螯合物适合于标记放射性砷（72 As：2.49 MeV β+，26 h; 77 As：0.683 MeV β-，38.8 h）以形成用于正电子发射断层扫描（PET）成像和治疗的潜在治疗诊断放射性药物。合成并表征了三巯基（B）-（Ser）2-RM 2生物缀合物及其砷配合物。三巯基（B）-（Ser）2-RM 2生物缀合物用无载体添加的77 As以超过95%的放射化学产率进行放射性标记，并且稳定超过48 h，并且[77 As]-三巯基（B）-（Ser）2-RM 2在PC-3细胞中的体外IC 50细胞结合研究证明了对胃泌素释放肽（GRP）受体的高亲和力（低纳摩尔范围）。用HPLC纯化的~（77）As-三硫醇（B）-（Ser）2-RM 2在正常小鼠中进行了有限的生物分布研究，证实了胰腺摄取和肝胆清除。
Trithiol chelates are suitable for labeling radioarsenic (72As: 2.49 MeV β+, 26 h;77As: 0.683 MeV β–, 38.8 h) to form potential theranostic radiopharmaceuticals for positron emission tomography (PET) imaging and therapy. A trithiol(b)-(Ser)2-RM2 bioconjugate and its arsenic complex were synthesized and characterized. The trithiol(b)-(Ser)2-RM2 bioconjugate was radiolabeled with no-carrier-added77As in over 95% radiochemical yield and was stable for over 48 h, andin vitroIC50cell binding studies of [77As]As-trithiol(b)-(Ser)2-RM2 in PC-3 cells demonstrated high affinity for the gastrin-releasing peptide (GRP) receptor (low nanomolar range). Limited biodistribution studies in normal mice were performed with HPLC purified77As-trithiol(b)-(Ser)2-RM2 demonstrating both pancreatic uptake and hepatobiliary clearance.