Patel Anand S, Saeed Maythem, Yee Erin J, Yang Jeffrey, Lam Gregory J, Losey Aaron D, Lillaney Prasheel V, Thorne Bradford, Chin Albert K, Malik Sheena, Wilson Mark W, Chen Xi C, Balsara Nitash P, Hetts Steven W
Department of Radiology and Biomedical Imaging, University of California San Francisco , 185 Berry Street, Suite 350, San Francisco, CA 94107-5705 e-mail:
Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
J Med Device. 2014 Dec;8(4):0410081-410088. doi: 10.1115/1.4027444. Epub 2014 Aug 19.
To develop a novel endovascular chemotherapy filter (CF) able to remove excess drug from the blood during intra-arterial chemotherapy delivery (IAC), thus preventing systemic toxicities and thereby enabling higher dose IAC. A flow circuit containing 2.5 mL of ion-exchange resin was constructed. Phosphate-buffered saline (PBS) containing 50 mg doxorubicin (Dox) was placed in the flow model with the hypothesis that doxorubicin would bind rapidly to resin. To simulate IAC, 50 mg of doxorubicin was infused over 10 min into the flow model containing resin. Similar testing was repeated with porcine serum. Doxorubicin concentrations were measured over 60 min and compared to controls (without resin). Single-pass experiments were also performed. Based on these experiments, an 18F CF was constructed with resin in its tip. In a pilot porcine study, the device was deployed under fluoroscopy. A control hepatic doxorubicin IAC model (no CF placed) was developed in another animal. A second CF device was created with a resin membrane and tested in the infrarenal inferior vena cava (IVC) of a swine. In the PBS model, resin bound 76% of doxorubicin in 10 min, and 92% in 30 min (P0.001). During IAC simulation, 64% of doxorubicin bound in 10 min and 96% in 60 min (P0.001). On average, 51% of doxorubicin concentration was reduced during each pass in single pass studies. In porcine serum, 52% of doxorubicin bound in 10 min, and 80% in 30 min (P0.05). CF device placement and administration of IAC were successful in three animals. No clot was present on the resin within the CF following the in vivo study. The infrarenal IVC swine study demonstrated promising results with up to 85% reduction in peak concentration by the CF device. An endovascular CF device was developed and shown feasible in vitro. An in vivo model was established with promising results supporting high-capacity rapid doxorubicin filtration from the blood that can be further evaluated in future studies.
开发一种新型血管内化疗滤器（CF），该滤器能够在动脉内化疗给药（IAC）期间从血液中去除过量药物，从而预防全身毒性反应，进而实现更高剂量的IAC。构建了一个包含2.5毫升离子交换树脂的流动回路。将含有50毫克阿霉素（Dox）的磷酸盐缓冲盐水（PBS）置于流动模型中，假设阿霉素会迅速与树脂结合。为模拟IAC，将50毫克阿霉素在10分钟内注入含有树脂的流动模型中。用猪血清重复进行类似测试。在60分钟内测量阿霉素浓度，并与对照组（无树脂）进行比较。还进行了单程实验。基于这些实验，构建了一种18F CF，其尖端含有树脂。在一项猪的前期研究中，该装置在荧光透视引导下进行了部署。在另一只动物身上建立了一个对照肝阿霉素IAC模型（未放置CF）。制作了第二个带有树脂膜的CF装置，并在一头猪的肾下下腔静脉（IVC）中进行了测试。在PBS模型中，树脂在10分钟内结合了76%的阿霉素，在30分钟内结合了92%（P<0.001）。在IAC模拟过程中，64%的阿霉素在10分钟内结合，96%在60分钟内结合（P<0.001）。在单程研究中，每次通过时阿霉素浓度平均降低51%。在猪血清中，52%的阿霉素在10分钟内结合，80%在30分钟内结合（P<0.05）。CF装置的放置和IAC给药在三只动物中均成功。体内研究后，CF内树脂上未出现血栓。肾下IVC猪的研究显示了有前景的结果，CF装置使峰值浓度降低了高达85%。开发了一种血管内CF装置，并在体外证明是可行的。建立了一个体内模型，其结果有前景，支持从血液中高效快速过滤阿霉素，可在未来研究中进一步评估。
