Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness
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...
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Nature Portfolio
2017
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oai:doaj.org-article:032c680d6f0045e89e611e90cded6e1d2021-12-02T16:07:46ZQuantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness10.1038/s41598-017-06534-z2045-2322https://doaj.org/article/032c680d6f0045e89e611e90cded6e1d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06534-zhttps://doaj.org/toc/2045-2322Abstract 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.Kohsuke GondaMika WatanabeHiroshi TadaMinoru MiyashitaYayoi Takahashi-AoyamaTakashi KameiTakanori IshidaShin UsamiHisashi HirakawaYoichiro KakugawaYohei HamanakaRyuichi YoshidaAkihiko FurutaHisatake OkadaHideki GodaHiroshi NegishiKensaku TakanashiMasaru TakahashiYuichi OzakiYuka YoshiharaYasushi NakanoNoriaki OhuchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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DOAJ |
| collection |
DOAJ |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 Yoshihara Yasushi Nakano Noriaki Ohuchi Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness |
| description |
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. |
| format |
article |
| author |
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 Yoshihara Yasushi Nakano Noriaki Ohuchi |
| author_facet |
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 Yoshihara Yasushi Nakano Noriaki Ohuchi |
| author_sort |
Kohsuke Gonda |
| title |
Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness |
| title_short |
Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness |
| title_full |
Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness |
| title_fullStr |
Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness |
| title_full_unstemmed |
Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness |
| title_sort |
quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/032c680d6f0045e89e611e90cded6e1d |
| work_keys_str_mv |
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