title: Development of photostabilized asymmetrical cyanine dyes for in vivo photoacoustic imaging of tumors.
abstract: Photoacoustic imaging (PAI) contributes to tumor diagnosis through the use of PAI probes that effectively accumulate in tumors. Previously, we developed a symmetrical cyanine dye, IC7-1-Bu, which showed high potential as a PAI probe because of its high tumor targeting ability and sufficient in vivo PA signal. However, IC7-1-Bu lacks photostability for multiple laser irradiations, so we developed stabilized PAI probes using IC7-1-Bu as a lead compound. We focused on the effect of singlet oxygen (1O2) generated by excited PAI probes on probe degeneration. We introduced a triplet-state quencher (TSQ) moiety into IC7-1-Bu to quench 1O2 generation and designed three IC-n-T derivatives with different linker lengths (n indicates linker length). The IC-n-T derivatives emitted in vitro PA signals that were comparable to IC7-1-Bu and significantly reduced 1O2 generation while showing improved photostability against multiple irradiations. Of the three derivatives evaluated, IC-5-T accumulated in tumors effectively to allow clear PAI of tumors in vivo. Furthermore, the photostability of IC-5-T was 1.5-fold higher than that of IC7-1-Bu in in vivo sequential PAI. These results suggest that IC-5-T is a potential PAI probe for in vivo sequential tumor imaging.
authors.affiliation: Kyoto University, Graduate School of Pharmaceutical Sciences, Department of Patho-Functional Bioanalysis, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Onoe
authors.affiliation: Kyoto University, Graduate School of Pharmaceutical Sciences, Department of Patho-Functional Bioanalysis, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapanbNational Cerebral and Cardiovascular Center Research Institute, Department of Investig.
authors.forename: Takashi
authors.initials: T
authors.lastname: Temma
authors.affiliation: Kyoto University, Graduate School of Pharmaceutical Sciences, Department of Patho-Functional Bioanalysis, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapancCanon Inc., Corporate R&D Headquarters, Medical Imaging Project, 3-30-2 Shimomaruko, O.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kanazaki
authors.affiliation: Kyoto University, Graduate School of Pharmaceutical Sciences, Department of Patho-Functional Bioanalysis, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Kyoto University, Graduate School of Pharmaceutical Sciences, Department of Patho-Functional Bioanalysis, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry* / Q000378:metabolism; D004396:Coloring Agents / Q000737:chemistry*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology*; D061848:Optical Imaging / Q000379:methods*; D061088:Photoacoustic Techniques / Q000379:methods*; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism
chemical_list: D002232:Carbocyanines; D004396:Coloring Agents; D012710:Serum Albumin, Bovine