Sosna Jacob, Havivi Ehud, Khan Wahid, Appelbaum Liat, Nyska Abraham, Domb Abraham J
Department of Radiology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel; Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Contrast Media Mol Imaging. 2014 May-Jun;9(3):246-51. doi: 10.1002/cmmi.1560.
Targeted delivery of drug-loaded implants for regional drug therapy has become an important approach to therapy. Simple and reproducible imaging methodologies to evaluate the implant noninvasively are needed. The goal of this work was to noninvasively evaluate the visibility, shape and degradation of a biodegradable implant containing Lipiodol (an X-ray contrast medium) by computed tomography (CT). For in vitro evaluation, Lipiodol was incorporated in poly(sebacic-co-ricinoleic acid) [P(SA:RA)], a biodegradable injectable pasty polymer, and CT visibility was assessed. For ex vivo evaluation, bovine liver was injected with the polymer-loaded Lipiodol; for in vivo evaluation rats were injected subcutaneously with Lipiodol in polymer and CT was performed. We show that polymer diameter at CT correlates with implant weight and pathological measurements. Polymer formulation containing 5% Lipiodol was visible on CT in vitro. Ex vivo tests showed a round polymer deposit at the injection site compared with free dispersion of Lipiodol alone. Correlation between implant size at CT scan and surgery at 48 h was R(2) = 0.78. Average CT diameter at 9 days was 14.2 ± 2.8 mm in rats injected with Lipiodol in the polymer formulation, as compared with 7.3 ± 1.1 mm in controls. After 9 days, the implant degraded into several zones containing inflammatory cells seen on CT as areas with increased heterogeneity. In conclusion, Lipiodol incorporated in P(SA:RA) is visible on CT, and polymer degradation can potentially be monitored noninvasively. This method can be widely applied to follow changes in biodegradable implants.
用于区域药物治疗的载药植入物的靶向递送已成为一种重要的治疗方法。需要简单且可重复的成像方法来无创评估植入物。这项工作的目标是通过计算机断层扫描（CT）无创评估含有碘油（一种X射线造影剂）的可生物降解植入物的可视性、形状和降解情况。对于体外评估，将碘油掺入聚（癸二酸-共-蓖麻油酸）[P(SA:RA)]（一种可生物降解的可注射糊状聚合物）中，并评估CT可视性。对于离体评估，将负载聚合物的碘油注入牛肝；对于体内评估，将聚合物中的碘油皮下注射到大鼠体内并进行CT检查。我们表明，CT上的聚合物直径与植入物重量和病理测量结果相关。含5%碘油的聚合物制剂在体外CT上可见。离体试验显示，与单独碘油的自由分散相比，注射部位有圆形聚合物沉积物。CT扫描时植入物大小与48小时后手术情况之间的相关性为R(2) = 0.78。在聚合物制剂中注射碘油的大鼠，9天时CT平均直径为14.2±2.8毫米，而对照组为7.3±1.1毫米。9天后，植入物降解为几个含有炎性细胞的区域，在CT上表现为异质性增加的区域。总之，掺入P(SA:RA)的碘油在CT上可见，并且可以潜在地无创监测聚合物降解。这种方法可广泛应用于跟踪可生物降解植入物的变化。
