Abstract：
The purpose of this article is to evaluate feasibility and safety of the cancer targeting (radio)-chemoembolization 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, lutetium-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.
摘要：
本文的目的是评估癌症靶向（放射）-化学栓塞药物洗脱珠（TRCE-DEB）概念药物SW43-DOX-L-NETA（89Y）DEB用于动脉内治疗的可行性和安全性。VX2兔肝肿瘤。所述治疗化合物包含用于癌症靶向的σ-2受体配体SW43,多柔比星（DOX），和89钇（89Y）作为非放射性替代品，用于通过螯合剂L-NETA治疗（钇90，钇177）和成像（钇86）放射性同位素。使用10只具有VX2肿瘤同种异体移植物的新西兰白兔。合成了SW43-DOX-89Y,加载到DEB（100μL；100-300μm），并以增加的剂量（0.2-1.0mg/kg）对六只兔子进行动脉内给药。作为控制，两只兔子分别接受阿霉素静脉注射(0.3mg/kg)或不接受治疗.处死后进行安全性和组织病理学评估的连续血清分析。单向方差分析，包括。进行Bonferroni事后检验以比较各组。靶向化合物合成，加载到DEB,动脉内给药在所有情况下都是可行和成功的。对于加载到DEB上的0.2/0.6mg/kgSW43-DOX-89Y，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。用1mg/kgSW43-DOX-89Y处理的两只兔子必须在3/24小时后安乐死,因为一般状况恶化。组织病理学坏死以剂量依赖性方式随时间增加,在治疗后3-7天(0.6mg/kg)具有95-100%肿瘤坏死。可以配制加载到DEB上的SW43-DOX-89Y并以0.6mg/kg的浓度安全施用。装载放射性同位素(例如，86钇/90钇/177钇)合成靶向放射-化学栓塞药物洗脱珠(TRCE-DEB)概念药物是可行的。
