Supervised in vivo lung perfusion strategy for treatment of cancer metastases to the lungs. Real time monitoring of chemotherapy by on-site analytical platform

约30%死于癌症的患者发生肺转移。手术切除肺转移瘤联合静脉全身化疗的效果相对较差，可能是由于耐药和无法在肺内达到有效的药物浓度。本研究的目的是使用一种叫做体外分离肺灌注（IVLP）的方法，这种方法在理论上具有选择性地输送药物和分流静脉流出物的优势。这使得药物可以以更高的剂量输送，而对药物相对敏感的关键器官中的药物水平保持在足够低的水平，以避免严重的副作用。为了优化抗癌药物到离体肺的输送，监测药物浓度及其在器官中的分布，并最终评估药物对肺的影响，需要可靠的分析方法，允许快速分析和最小的侵入性。为此，我们提出了一种新的方法，即固相微萃取（SPME），该技术利用涂有生物相容性聚合物的微探针直接插入组织中，无需收集活检样本即可提取小分子。据推测，由于涂层的性质，我们不仅可以观察药物浓度，而且可以观察到器官代谢谱的快速变化，作为对所用化疗药物的反应。我们还建议开发一种将SPME与一种质谱技术相结合的策略，以便实时检测分析物。该组合可作为术中快速监测药物水平和治疗进展的工具。

Pulmonary metastases occur in approximately 30% of patients dying of cancer. The relatively poor results of surgicalresection of pulmonary metastases combined with intravenous systemic chemotherapy are probably due to drug resistanceand the inability to achieve effective drug concentrations within the lung. The proposed research aim to use method called invivo isolated lung perfusion (IVLP), which has the theoretical advantage of both selectively delivering an agent and divertingthe venous effluent. This allows a drug to be delivered in a higher dose, while drug levels in critical organs that are relativelysensitive to the drug, are kept low enough to avoid severe side effects. In order to optimize delivery of anticancer agent tothe isolated lungs, to monitor concentration of the drug and its distribution in the organ and finally to assess the effect of thedrug on the lungs the reliable analytical approach permitting rapid analysis and minimum invasiveness is required. For thispurpose we propose to use novel method called solid phase microextraction (SPME), the technology which utilizesmicroprobe coated with biocompatible polymer to be inserted directly into the tissue and extract small molecules with nonecessity of collection biopsy sample. It is postulated that due to the properties of the coating we can observe not only drugconcentration but also fast changes in metabolic profile of the organ as a response to the used chemotherapy in onesampling. We also propose to develop a strategy of coupling SPME with one of the mass spectrometry techniques enablingdetection of analytes in real time. This combination could be used as rapid intraoperative tool for monitoring ofdrug level and therapy progress.