Multi-wavelength photoacoustic imaging of inducible tyrosinase reporter gene expression in xenograft tumors

Sci Rep. 2014 Jun 17:4:5329. doi: 10.1038/srep05329.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Diagnostic Imaging / methods*
  • Doxycycline / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, Reporter / genetics
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Melanins / metabolism
  • Mice, SCID
  • Monophenol Monooxygenase / genetics*
  • Monophenol Monooxygenase / metabolism
  • Photoacoustic Techniques / methods
  • Reproducibility of Results
  • Spectrum Analysis / methods
  • Xenograft Model Antitumor Assays*

Substances

  • Anti-Bacterial Agents
  • Melanins
  • Monophenol Monooxygenase
  • Doxycycline