Quantitative Diagnostic Imaging of Cancer Tissues by Using Phosphor-integrated Dots with Ultra-high Brightness

Overview

Journal Sci Rep

Specialty Science

Date 2017 Aug 10

PMID 28790306

Citations 16

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Excess fibroblast growth factor 23 in alcoholic osteomalacia is derived from the bone.

Hidaka N, Oyama Y, Koga M, Kondo N, Yasunaga Y, Shimakura T JBMR Plus. 2025; 9(3):ziaf010.

PMID: 39963340 PMC: 11831984. DOI: 10.1093/jbmrpl/ziaf010.

Novel approach to HER2 quantification using phosphor-integrated dots in human breast invasive cancer microarray.

Saito N, Matsuo T, Tsuda H, Yokota H, Okada H PLoS One. 2024; 19(5):e0303614.

PMID: 38748758 PMC: 11095758. DOI: 10.1371/journal.pone.0303614.

The 4-1BBζ costimulatory domain in chimeric antigen receptors enhances CD8+ T-cell functionality following T-cell receptor stimulation.

Chu G, Bailey C, Nagarajah R, Sagnella S, Adelstein S, Rasko J Cancer Cell Int. 2023; 23(1):327.

PMID: 38105188 PMC: 10726568. DOI: 10.1186/s12935-023-03171-7.

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors.

Ohkuma R, Miura S, Muto S, Toyomasu Y, Fujimoto Y, Ieguchi K Front Immunol. 2023; 14:1260492.

PMID: 37790929 PMC: 10544572. DOI: 10.3389/fimmu.2023.1260492.

Review of the Role of Nanotechnology in Overcoming the Challenges Faced in Oral Cancer Diagnosis and Treatment.

Umapathy V, Natarajan P, Swamikannu B Molecules. 2023; 28(14).

PMID: 37513267 PMC: 10385509. DOI: 10.3390/molecules28145395.

References

Deerinck T . The application of fluorescent quantum dots to confocal, multiphoton, and electron microscopic imaging. Toxicol Pathol. 2008; 36(1):112-6. PMC: 2771444. DOI: 10.1177/0192623307310950. View

Verma S, Miles D, Gianni L, Krop I, Welslau M, Baselga J . Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012; 367(19):1783-91. PMC: 5125250. DOI: 10.1056/NEJMoa1209124. View

Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S . Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a.... Lancet. 2010; 375(9712):377-84. DOI: 10.1016/S0140-6736(09)61964-4. View

Gonda K, Miyashita M, Watanabe M, Takahashi Y, Goda H, Okada H . Development of a quantitative diagnostic method of estrogen receptor expression levels by immunohistochemistry using organic fluorescent material-assembled nanoparticles. Biochem Biophys Res Commun. 2012; 426(3):409-14. DOI: 10.1016/j.bbrc.2012.08.105. View

Aguilar Z, Akita R, Finn R, Ramos B, Pegram M, Kabbinavar F . Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells. Oncogene. 1999; 18(44):6050-62. DOI: 10.1038/sj.onc.1202993. View

Provenzano E, Bossuyt V, Viale G, Cameron D, Badve S, Denkert C . Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group. Mod Pathol. 2015; 28(9):1185-201. DOI: 10.1038/modpathol.2015.74. View

Hikage M, Gonda K, Takeda M, Kamei T, Kobayashi M, Kumasaka M . Nano-imaging of the lymph network structure with quantum dots. Nanotechnology. 2010; 21(18):185103. DOI: 10.1088/0957-4484/21/18/185103. View

Gonda K, Miyashita M, Higuchi H, Tada H, Watanabe T, Watanabe M . Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging. Sci Rep. 2015; 5:14322. PMC: 4585722. DOI: 10.1038/srep14322. View

Kohl C, Weil T, Qu J, Mullen K . Towards highly fluorescent and water-soluble perylene dyes. Chemistry. 2004; 10(21):5297-310. DOI: 10.1002/chem.200400291. View

10.

Camp R, Dolled-Filhart M, King B, Rimm D . Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome. Cancer Res. 2003; 63(7):1445-8. View

11.

Gao X, Cui Y, Levenson R, Chung L, Nie S . In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004; 22(8):969-76. DOI: 10.1038/nbt994. View

12.

Miyashita M, Gonda K, Tada H, Watanabe M, Kitamura N, Kamei T . Quantitative diagnosis of HER2 protein expressing breast cancer by single-particle quantum dot imaging. Cancer Med. 2016; 5(10):2813-2824. PMC: 5083734. DOI: 10.1002/cam4.898. View

13.

Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979; 76(9):4350-4. PMC: 411572. DOI: 10.1073/pnas.76.9.4350. View

14.

Camp R, Chung G, Rimm D . Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med. 2002; 8(11):1323-7. DOI: 10.1038/nm791. View

15.

Gonda K, Watanabe T, Ohuchi N, Higuchi H . In vivo nano-imaging of membrane dynamics in metastatic tumor cells using quantum dots. J Biol Chem. 2009; 285(4):2750-7. PMC: 2807330. DOI: 10.1074/jbc.M109.075374. View

16.

Swain S, Kim S, Cortes J, Ro J, Semiglazov V, Campone M . Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013; 14(6):461-71. PMC: 4076842. DOI: 10.1016/S1470-2045(13)70130-X. View

17.

Wu X, Liu H, Liu J, Haley K, Treadway J, Larson J . Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol. 2002; 21(1):41-6. DOI: 10.1038/nbt764. View

18.

Untch M, Rezai M, Loibl S, Fasching P, Huober J, Tesch H . Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010; 28(12):2024-31. DOI: 10.1200/JCO.2009.23.8451. View

19.

Perez E, Romond E, Suman V, Jeong J, Sledge G, Geyer Jr C . Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014; 32(33):3744-52. PMC: 4226805. DOI: 10.1200/JCO.2014.55.5730. View

20.

Lavabre-Bertrand T, Janossy G, Ivory K, Peters R, Porwit-Macdonald A . Leukemia-associated changes identified by quantitative flow cytometry: I. CD10 expression. Cytometry. 1994; 18(4):209-17. DOI: 10.1002/cyto.990180404. View