title: Optical molecular imaging approach for rapid assessment of response of individual cancer cells to chemotherapy.
abstract: 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.
authors.affiliation: Department of Biological and Agricultural Engineering, University of California-Davis, Old Davis Road, Davis, California 95616, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Luo
authors.forename: Rohan Vijay
authors.initials: RV
authors.lastname: Tikekar
authors.forename: Kiana Michelle
authors.initials: KM
authors.lastname: Samadzadeh
authors.forename: Nitin
authors.initials: N
authors.lastname: Nitin
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D008856:Microscopy, Fluorescence / Q000379:methods; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism
chemical_list: C417561:Alexa 488 hydrazide; D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D006834:Hydrazines; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose; D002794:Choline; D002945:Cisplatin