Azhdarinia Ali, Yang David J, Yu Dong-Fang, Mendez Richard, Oh Changsok, Kohanim Saady, Bryant Jerry, Kim E Edmund
Division of Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Pharm Res. 2005 May;22(5):776-83. doi: 10.1007/s11095-005-2594-7. Epub 2005 May 17.
To evaluate the feasibility of regional radiochemotherapy of mammary tumors using in situ hydrogel loaded with cisplatin (CDDP) and rhenium-188 ((188)Re).
Sodium alginate (SA) and calcium chloride were used to create a hydrogel for delivery of CDDP and (188)Re. In vitro studies were performed to evaluate cytotoxic effects of (188)Re-hydrogel and sustained-release ability of the CDDP-hydrogel. Tumor-bearing rats were injected with (188)Re-hydrogel (0.5-1 mCi/rat), (188)Re-perrhenate (0.5-1 mCi/rat, intratumoral, I.T.), CDDP-hydrogel (3 mg/kg), and (188)Re-hydrogel loaded with CDDP (3 mg/kg body weight, 0.5-1 mCi/rat), respectively, and groups receiving (188)Re were imaged at 24 and 48 h postinjection. Tumor volume, body weight, imaging, and kidney function were assessed as required for each group.
Successful formation of the hydrogel was demonstrated by cytotoxic effects of (188)Re-hydrogel and slow release of CDDP-hydrogel in vitro. Tumor volume measurements showed significant delay in tumor growth in treated vs. control groups with minimal variation in normal kidney function for the CDDP-hydrogel group. Scintigraphic images indicated localization of (188)Re-hydrogel in the tumor site up to 48 h postinjection.
Our data demonstrate the feasibility of using hydrogel for delivery of chemotherapeutics and radiation locally. This technique may have applications involving other contrast modalities as well as treatment in cases where tumors are inoperable.
评估使用负载顺铂(CDDP)和铼 - 188(¹⁸⁸Re)的原位水凝胶对乳腺肿瘤进行区域放化疗的可行性。
使用海藻酸钠(SA)和氯化钙制备用于递送CDDP和¹⁸⁸Re的水凝胶。进行体外研究以评估¹⁸⁸Re - 水凝胶的细胞毒性作用和CDDP - 水凝胶的缓释能力。分别给荷瘤大鼠注射¹⁸⁸Re - 水凝胶(0.5 - 1 mCi/只大鼠)、高铼酸盐¹⁸⁸Re(0.5 - 1 mCi/只大鼠,瘤内注射,I.T.)、CDDP - 水凝胶(3 mg/kg)以及负载CDDP的¹⁸⁸Re - 水凝胶(3 mg/kg体重,0.5 - 1 mCi/只大鼠),并且对接受¹⁸⁸Re注射的组在注射后24小时和48小时进行成像。根据需要对每组的肿瘤体积、体重、成像和肾功能进行评估。
¹⁸⁸Re - 水凝胶的细胞毒性作用和CDDP - 水凝胶在体外的缓慢释放证明了水凝胶的成功形成。肿瘤体积测量显示,与对照组相比,治疗组肿瘤生长明显延迟,而CDDP - 水凝胶组的正常肾功能变化最小。闪烁图像表明,¹⁸⁸Re - 水凝胶在注射后48小时内定位在肿瘤部位。
我们的数据证明了使用水凝胶局部递送化疗药物和放疗的可行性。该技术可能在涉及其他造影方式以及肿瘤无法手术切除的病例治疗中具有应用价值。