Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness

Kohsuke Gonda, Mika Watanabe, Hiroshi Tada, Minoru Miyashita, Yayoi Takahashi-Aoyama, Takashi Kamei, Takanori Ishida, Shin Usami, Hisashi Hirakawa, Yoichiro Kakugawa, Yohei Hamanaka, Ryuichi Yoshida, Akihiko Furuta, Hisatake Okada, Hideki Goda, Hiroshi Negishi, Kensaku Takanashi, Masaru Takahashi, Yuichi Ozaki, Yuka YoshiharaYasushi Nakano, Noriaki Ohuchi

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13 Citations (Scopus)

Abstract

The quantitative sensitivity and dynamic range of conventional immunohistochemistry (IHC) with 3,3′-diaminobenzidine (IHC-DAB) used in pathological diagnosis in hospitals are poor, because enzyme activity can affect the IHC-DAB chromogenic reaction. Although fluorescent IHC can effectively increase the quantitative sensitivity of conventional IHC, tissue autofluorescence interferes with the sensitivity. Here, we created new fluorescent nanoparticles called phosphor-integrated dots (PIDs). PIDs have 100-fold greater brightness and a more than 300-fold greater dynamic range than those of commercially available fluorescent nanoparticles, quantum dots, whose fluorescence intensity is comparable to tissue autofluorescence. Additionally, a newly developed image-processing method enabled the calculation of the PID particle number in the obtained image. To quantify the sensitivity of IHC using PIDs (IHC-PIDs), the IHC-PIDs method was compared with fluorescence-activated cell sorting (FACS), a method well suited for evaluating total protein amount, and the two values exhibited strong correlation (R = 0.94). We next applied IHC-PIDs to categorize the response to molecular target-based drug therapy in breast cancer patients. The results suggested that the PID particle number estimated by IHC-PIDs of breast cancer tissues obtained from biopsy before chemotherapy can provide a score for predicting the therapeutic effect of the human epidermal growth factor receptor 2-targeted drug trastuzumab.

Original languageEnglish
Article number7509
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

ASJC Scopus subject areas

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    Gonda, K., Watanabe, M., Tada, H., Miyashita, M., Takahashi-Aoyama, Y., Kamei, T., Ishida, T., Usami, S., Hirakawa, H., Kakugawa, Y., Hamanaka, Y., Yoshida, R., Furuta, A., Okada, H., Goda, H., Negishi, H., Takanashi, K., Takahashi, M., Ozaki, Y., ... Ohuchi, N. (2017). Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness. Scientific reports, 7(1), [7509]. https://doi.org/10.1038/s41598-017-06534-z