Department of Biological and Agricultural Engineering, University of California-Davis, Old Davis Road, Davis, California 95616, USA.
J Biomed Opt. 2012 Oct;17(10):106006. doi: 10.1117/1.JBO.17.10.106006.
Predicting the response of individual patients to cytotoxic chemotherapy drugs is critical for developing individualized therapies. With this motivation, an optical molecular imaging approach was developed to detect cisplatin induced changes in the uptake and intracellular retention of choline. Intracellular uptake of choline was characterized using a click chemistry reaction between propargyl choline and Alexa-488 azide. Cisplatin induced changes in the uptake of propargyl choline in cells and tumor spheroids were compared with similar measurements using a fluorescent analogue of deoxyglucose and conventional cell viability assays. Uptake and intracellular retention of propargyl choline decreased with an increase in concentration of cisplatin. Intracellular uptake of propargyl choline was significantly reduced within 3 h of incubation with a sub-lethal dose of cisplatin. Results demonstrate that the imaging approach based on propargyl choline was more sensitive in detecting the early response of cancer cells to cisplatin as compared to the imaging based on fluorescent analogue of deoxyglucose and cell viability assays. Imaging measurements in tumor spheroids show a significant decrease in the uptake of propargyl choline following treatment with cisplatin. Overall, the results demonstrate a novel optical molecular imaging approach for rapid measurement of the response of individual cancer cells to cisplatin treatment.
预测个体患者对细胞毒性化疗药物的反应对于开发个体化治疗至关重要。基于这一动机，开发了一种光学分子成像方法来检测顺铂诱导的胆碱摄取和细胞内保留的变化。使用炔丙基胆碱与 Alexa-488 叠氮化物之间的点击化学反应来表征细胞内摄取的胆碱。将顺铂诱导的细胞和肿瘤球体中炔丙基胆碱摄取的变化与使用脱氧葡萄糖的荧光类似物和常规细胞活力测定进行的类似测量进行了比较。随着顺铂浓度的增加，炔丙基胆碱的摄取和细胞内保留减少。在孵育亚致死剂量的顺铂 3 小时内，炔丙基胆碱的细胞内摄取显著降低。结果表明，与基于脱氧葡萄糖的荧光类似物和细胞活力测定的成像方法相比，基于炔丙基胆碱的成像方法在检测癌细胞对顺铂的早期反应方面更敏感。在肿瘤球体中的成像测量表明，在用顺铂处理后，炔丙基胆碱的摄取明显减少。总的来说，该结果证明了一种新的光学分子成像方法，可用于快速测量个体癌细胞对顺铂治疗的反应。
