title: Multi-wavelength photoacoustic imaging of inducible tyrosinase reporter gene expression in xenograft tumors.
abstract: Photoacoustic imaging is an emerging hybrid imaging technology capable of breaking through resolution limits of pure optical imaging technologies imposed by optical-scattering to provide fine-resolution optical contrast information in deep tissues. We demonstrate the ability of multi-wavelength photoacoustic imaging to estimate relative gene expression distributions using an inducible expression system and co-register images with hemoglobin oxygen saturation estimates and micro-ultrasound data. Tyrosinase, the rate-limiting enzyme in melanin production, is used as a reporter gene owing to its strong optical absorption and enzymatic amplification mechanism. Tetracycline-inducible melanin expression is turned on via doxycycline treatment in vivo. Serial multi-wavelength imaging reveals very low estimated melanin expression in tumors prior to doxycycline treatment or in tumors with no tyrosinase gene present, but strong signals after melanin induction in tumors tagged with the tyrosinase reporter. The combination of new inducible reporters and high-resolution photoacoustic and micro-ultrasound technology is poised to bring a new dimension to the study of gene expression in vivo.
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 2V4, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Paproski
authors.affiliation: FUJIFILM VisualSonics, Inc., Toronto, Ontario M4N 3N1, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Heinmiller
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta T6G 1Z2, Canada.
authors.forename: Keith
authors.initials: K
authors.lastname: Wachowicz
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 2V4, Canada.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Zemp
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D016513:Mice, SCID; D014442:Monophenol Monooxygenase / Q000235:genetics* / Q000378:metabolism; D061088:Photoacoustic Techniques / Q000379:methods; D015203:Reproducibility of Results; D013057:Spectrum Analysis / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; D008543:Melanins; D014442:Monophenol Monooxygenase; D004318:Doxycycline