Development of a Human Photoacoustic Imaging Reporter Gene Using the Clinical Dye Indocyanine Green.

PURPOSE

To develop a photoacoustic imaging (PAI) reporter gene that has high translational potential. Previous research has shown that human organic anion-transporting polypeptide 1b3 (OATP1B3) promotes the uptake of the near-infrared fluorescent dye indocyanine green (ICG). In this study, the authors have established and ICG as a reporter gene-probe pair for in vivo PAI.

MATERIALS AND METHODS

Human breast cancer cells were engineered to express . Control cells (not expressing ) or -expressing cells were incubated with or without ICG, placed in a breast-mimicking phantom, and imaged with PAI. Control ( = 6) or -expressing ( = 5) cells were then implanted orthotopically into female mice. Full-spectrum PAI was performed before and 24 hours after ICG administration. One-way analysis of variance was performed, followed by Tukey posthoc multiple comparisons, to assess statistical significance.

RESULTS

-expressing cells incubated with ICG exhibited a 2.7-fold increase in contrast-to-noise ratio relative to all other controls in vitro ( < .05). In mice, PAI signals after ICG administration were increased 2.3-fold in OATP1B3 tumors relative to those in controls ( < .05).

CONCLUSION

operates as an in vivo PAI reporter gene based on its ability to promote the cellular uptake of ICG. Benefits include the human derivation of , combined with the use of wavelengths in the near-infrared region, high extinction coefficient, low quantum yield, and clinical approval of ICG. The authors posit that this system will be useful for localized monitoring of emerging gene- and cell-based therapies in clinical applications.© RSNA, 2019 Animal Studies, Molecular Imaging, Molecular Imaging-Clinical Translation, Molecular Imaging-Reporter Gene Imaging, Optical Imaging