title: An optimized triple modality reporter for quantitative in vivo tumor imaging and therapy evaluation.
abstract: We present an optimized triple modality reporter construct combining a far-red fluorescent protein (E2-Crimson), enhanced firefly luciferase enzyme (Luc2), and truncated wild type herpes simplex virus I thymidine kinase (wttk) that allows for sensitive, long-term tracking of tumor growth in vivo by fluorescence, bioluminescence, and positron emission tomography. Two human cancer cell lines (MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer) were successfully transduced to express this triple modality reporter. Fluorescence and bioluminescence imaging of the triple modality reporter were used to accurately quantify the therapeutic responses of MDA-MB-231 tumors to the chemotherapeutic agent monomethyl auristatin E in vivo in athymic nude mice. Positive correlation was observed between the fluorescence and bioluminescence signals, and these signals were also positively correlated with the ex vivo tumor weights. This is the first reported use of both fluorescence and bioluminescence signals from a multi-modality reporter construct to measure drug efficacy in vivo.
authors.affiliation: Department of Pharmacology, UCSD School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Levin
authors.affiliation: Department of Pharmacology, UCSD School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Csilla N
authors.initials: CN
authors.lastname: Felsen
authors.affiliation: Department of Pharmacology, UCSD School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, UCSD School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: John Y
authors.initials: JY
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, UCSD School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Whitney
authors.affiliation: Division of Otolaryngology/Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Quyen T
authors.initials: QT
authors.lastname: Nguyen
authors.affiliation: Department of Pharmacology, UCSD School of Medicine, University of California San Diego, La Jolla, California, United States of America; Howard Hughes Medical Institute, La Jolla, California, United States of America.
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Tsien
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005453:Fluorescence; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006801:Humans; D008156:Luciferases; D008163:Luminescent Measurements / Q000379:methods; D008164:Luminescent Proteins; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013937:Thymidine Kinase; D014161:Transduction, Genetic; D000097573:Red Fluorescent Protein
chemical_list: D008156:Luciferases; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D013937:Thymidine Kinase; D000097573:Red Fluorescent Protein