Adjuvant Liposomal Doxorubicin Markedly Affects Radiofrequency Ablation-induced Effects on Periablational Microvasculature

作者：Moussa Marwan^*; Goldberg S Nahum; Tasawwar Beenish; Sawant Rupa R; Levchenko Tatyana; Kumar Gaurav; Torchilin Vladimir P; Ahmed Muneeb

来源：Journal of Vascular and Interventional Radiology, 2013, 24(7): 1021-1033.

DOI：10.1016/j.jvir.2013.03.006

Purpose: To evaluate the effects of radiofrequency (RF) ablation without and with adjuvant intravenous (IV) liposomal doxorubicin (Doxil) on microvessel morphology and patency and intratumoral drug delivery and retention.
Materials and Methods: There were 133 tumors/animals used in this experiment. First, single subcutaneous tumors (R3230 in Fischer rats and 786-0 in nude mice) were randomly assigned to receive RE ablation alone or no treatment and sacrificed 0-72 hours after treatment. Next, combined RF ablation and liposomal doxorubicin (1 mg given 15 min after RF ablation) was studied in R3230 tumors at 0-72 hours after treatment. Histopathologic assessment, including immunohistochemical staining for cleaved caspase-3, heat-shock protein 70, and CD34, was performed to assess morphologic vessel appearance, vessel diameter, and microvascular density. Subsequently; tumors were randomly assigned to receive RF ablation alone, RF ablation and liposomal doxorubicin, or no treatment (control tumors), followed by IV fluorescent-labeled liposomes (a surrogate marker) given 0-24 hours after RF ablation to permit qualitative assessment.
Results: RF ablation alone resulted in enlarged and dysmorphic vessels from 0-4 hours, peaking at 12-24 hours after RF ablation, occurring preferentially closer to the electrode. The addition of doxorubicin resulted in earlier vessel contraction (Mean vessel area, 47,539 mu m(2) +/- 9,544 vs 1,854 mu m(2) +/- 458 for RF ablation alone at 15 min; P < .05). Combined RF ablation and liposomal doxorubicin produced similar fluorescence 1 hour after treatment (40.88 AU/mu m(2) +/- 33.53 vs 22.1 AU/mu m(2) +/- 13.19; P = .14) but significantly less fluorescence at 4 hours (24.3 AU/mu m(2) +/- 3.65 vs 2.8 AU/mu m(2) +/- 3.14; P < .002) compared with RF ablation alone denoting earlier reduction in microvascular patency.
Conclusions: RF ablation induces morphologic changes to vessels within the ablation zone lasting 12-24 hours after treatment. The addition of liposomal doxorubicin causes early vessel contraction and a reduction in periablational microvascular patency. Such changes would likely need to be considered when determining optimal drug administration and imaging paradigms.

• 出版日期2013-7
• 单位东北大学