A human photoacoustic imaging reporter gene using the clinical dye indocyanine green

Abstract

Photoacoustic imaging (PAI) combines optical contrast with the resolution and depthdetection of ultrasound and is increasingly being utilized for medical imaging in patients.PAI reporter genes would allow for monitoring of cell and gene therapies, but current reporters have immunogenicity and/or toxicity concerns that may limit clinical translation.Here we report a PAI reporter system employing the ability of human organic anion transporting polypeptide 1b3 (Oatp1b3) to take up the clinical dye indocyanine green (ICG) into cells. Following ICG administration, cells synthetically expressing Oatp1b3 exhibited significantly increased PAI signals compared to control cells both in vitro and in mice. Several benefits of this technology are the human derivation of Oatp1b3, and the high extinction coefficient, low quantum yield and pre-existing clinical approval of ICG.We posit that the Oatp1b3-ICG reporter system could be useful for in vivo gene and cell tracking in preclinical and clinical applications.

Utility of Hepatic Transporters as Multimodal Gene Reporters for Cell‐Based Medicine

“…Recently, Ronald et al have demonstrated that OATP1B3‐expressing orthotopic breast tumors can uptake sufficient ICG dye, which can generate quantifiable acoustic waves that are detectable by photoacoustic imager (PAI). [ 41 ] Meanwhile, Patrick et al showed an exchange of Gd3 + ion with 111 Indium radionucleotide, which allowed the rodent Oatp1a1 reporter to be detected on SPECT. [ 10 ] These data suggest that OATP1B1 and OATP1B3 are potential indirect reporter for SPECT imaging.…”

Listening for the therapeutic window: Advances in drug delivery utilizing photoacoustic imaging

“…However, most reported contrast agents can only provide information about the location of the implanted labeled cells with limited information about the cell number in vivo. It is possible that photoacoustic reporter gene techniques may overcome some of the existing limitations, especially ones that leverage dyes with existing FDA approval [124]. Nevertheless, tremendous and revolutionary research on multiple imaging modalities and contrast agents is still needed to fully understand the therapeutic efficacy and cell fate of stem cell therapies [102].…”