Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 µL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 µL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors.

中文翻译：

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聚合物辅助肿瘤内乙醇的递送：在鼠类乳腺癌模型中安全性和有效性的临床前研究

由于乙醇的总体成本较低，影像技术要求最低且临床结果可接受，因此使用乙醇进行局灶性肿瘤消融可在资源贫乏的地区提供益处。不幸的是，由于消融区缺乏可预测性，乙醇消融区不常使用，消融区是由于乙醇在注射部位的滞留不足而引起的。为了创建可预测的消融区域，我们开发了一种使用乙基纤维素（EC）与乙醇混合的聚合物辅助消融方法。EC是溶于乙醇的和不溶于水的，允许EC-乙醇以液体形式注入并沉淀成固体，从而阻止了乙醇与组织接触后的泄漏。这项研究的目的是比较1）安全性，2）释放动力学，3）空间分布，4）坏死体积，5）在小鼠乳腺肿瘤模型中EC-乙醇相对于常规乙醇消融的总体存活率。非目标组织损伤通过局部不良事件记录，拉曼光谱法观察乙醇释放动力学，体内成像注射分布，NADH-黄递酶染色对靶组织坏死以及通过肿瘤生长的总体存活率进行监测。与相同体积的纯乙醇相比，EC-乙醇显示出减少的局部不良事件，乙醇的释放速率减慢，注射区更紧凑，靶组织坏死增加5倍，总生存率更长。单次150 µL剂量的6％EC-乙醇的存活概率与每天六次50 µL的纯乙醇（用于模拟6天内乙醇的缓慢释放）的存活率相似。在一起