Targeted Yttrium 89-Doxorubicin Drug-Eluting Bead-A Safety and Feasibility Pilot Study in a Rabbit Liver Cancer Model.
Targeted Yttrium 89-Doxorubicin Drug-Eluting Bead-A Safety and Feasibility Pilot Study in a Rabbit Liver Cancer Model.
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DOI：
10.1021/acs.molpharmaceut.7b00336
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发表时间：
2017-08-07
影响因子：
4.9
通讯作者：
Kim HS
中科院分区：
文献类型：
--
作者：
Ludwig JM;Xing M;Gai Y;Sun L;Zeng D;Kim HS
本文的目的是评价肿瘤靶向（放射性）化疗栓塞药物洗脱珠（TRCE-DEB）概念药物SW 43-DOX-L-NETA（89 Y）DEB动脉内治疗VX 2兔肝肿瘤的可行性和安全性。治疗化合物包含用于癌症靶向的σ-2受体配体SW 43、阿霉素（DOX）和89钇（89 Y），所述89钇（89 Y）通过螯合剂L-NETA作为治疗（钇-90、镥-177）和成像（钇-86）放射性同位素的非放射性替代物。使用10只新西兰白色兔与VX 2肿瘤同种异体移植物。合成SW 43-DOX-89 Y，加载到DEB（100 μL; 100-300 μm）上，并以递增剂量（0.2-1.0 mg/kg）动脉内给药6只家兔。作为对照，两只家兔分别接受多柔比星IV（0.3 mg/kg）或不接受治疗。处死后进行安全性对比性血清分析和组织病理学评价。单因素方差分析，包括进行Bonferroni事后检验以比较各组。靶向化合物合成、装载到DEB上和动脉内给药在所有情况下都是可行和成功的。对于装载到DEB上的0.2/0.6 mg/kg SW 43-DOX-89 Y，血清肝酶水平在24小时内以剂量依赖性方式增加，并在3天内恢复正常。接受1 mg/kg SW 43-DOX-89 Y治疗的两只兔子不得不在3/24小时后因一般状况恶化而被安乐死。组织学坏死以剂量依赖性方式随时间增加，给药后3-7天（0.6 mg/kg）肿瘤坏死95-100%。装载到DEB上的SW 43-D 0X-89 Y可以配制并以0.6mg/kg的浓度安全地施用。装载放射性同位素（例如，86钇/90钇/177镥）合成靶向放化栓塞药物洗脱珠（TRCE-DEB）概念药物是可行的。
The purpose of this article is to evaluate feasibility and safety of the cancer targeting (radio)-chemo-embolization drug-eluting bead (TRCE-DEB) concept drug SW43-DOX-L-NETA(89Y) DEB for the intra-arterial treatment of VX2 rabbit liver tumors. The treatment compound comprises of the sigma-2 receptor ligand SW43 for cancer targeting, doxorubicin (DOX), and 89yttrium (89Y) as nonradioactive surrogate for therapeutic (yttrium-90, luteti-um-177) and imaging (yttrium-86) radioisotopes via the chelator L-NETA. Ten New Zealand white rabbits with VX2 tumor allografts were used. SW43-DOX-89Y was synthesized, loaded onto DEB (100 μL; 100–300 μm), and administered intra-arterially in six rabbits at increasing doses (0.2–1.0 mg/kg). As controls, two rabbits each received either doxorubicin IV (0.3 mg/kg) or no treatment. Consecutive serum analysis for safety and histopathological evaluation after sacrifice were performed. One-Way ANOVA incl. Bonferroni Post-Hoc test was performed to compare groups. Targeted compound synthesis, loading onto DEB, and intra-arterial administration were feasible and successful in all cases. Serum liver enzyme levels increased in a dose dependent manner within 24 h and normalized within 3 days for 0.2/0.6 mg/kg SW43-DOX-89Y loaded onto DEB. The two rabbits treated with 1 mg/kg SW43-DOX-89Y had to be euthanized after 3/24 h due to worsening general condition. Histopathological necrosis increased over time in a dose depended manner with 95–100% tumor necrosis 3–7 days post treatment (0.6 mg/kg). SW43-DOX-89Y loaded onto DEB can be formulated and safely administered at a concentration of 0.6 mg/kg. Loading with radioactive isotopes (e.g., 86yttrium/90yttrium/177lutetium) to synthesize the targeted radio-chemoembolization drug-eluting bead (TRCE-DEB) concept drug is feasible.
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σ2受体：一种用于癌症成像和治疗的新型蛋白质。
影响因子：
7.3
作者：
Mach, Robert H.;Zeng, Chenbo;Hawkins, William G.
通讯作者：
Hawkins, William G.
影响因子：
2.1
作者：
Parvinian, Ahmad;Casadaban, Leigh C.;Gaba, Ron C.
通讯作者：
Gaba, Ron C.
影响因子：
37.3
作者：
Hornick, John R.;Xu, Jinbin;Hawkins, William G.
通讯作者：
Hawkins, William G.
影响因子：
5.9
作者：
Gholamrezanezhad A;Mirpour S;Geschwind JF;Rao P;Loffroy R;Pellerin O;Liapi EA
通讯作者：
Liapi EA
影响因子：
5.9
作者：
Ludwig, Johannes M.;Zhang, Di;Kim, Hyun S.
通讯作者：
Kim, Hyun S.