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Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness
Kohsuke Gonda1,2, Mika Watanabe3, Hiroshi Tada4
1Department of Medical Physics, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. gonda@med.tohoku.ac.jp.
Insights
New phosphor-integrated dots (PIDs) significantly enhance immunohistochemistry (IHC) sensitivity and dynamic range for better pathological diagnosis. This novel fluorescent nanoparticle method aids in predicting breast cancer drug response.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pathology
Background:
- Conventional immunohistochemistry (IHC) with 3,3'-diaminobenzidine (IHC-DAB) has poor quantitative sensitivity and dynamic range due to enzyme activity.
- Fluorescent IHC improves sensitivity but is hindered by tissue autofluorescence.
Purpose of the Study:
- To develop novel fluorescent nanoparticles, phosphor-integrated dots (PIDs), to overcome limitations of current IHC methods.
- To establish a highly sensitive and quantitative IHC method using PIDs (IHC-PIDs).
- To evaluate the potential of IHC-PIDs for predicting therapeutic response in breast cancer patients.
Main Methods:
- Creation of phosphor-integrated dots (PIDs) with superior brightness and dynamic range compared to quantum dots.
- Development of an image-processing method to quantify PID particle numbers.
- Validation of IHC-PIDs sensitivity and accuracy by comparison with fluorescence-activated cell sorting (FACS).
Main Results:
- PIDs exhibit 100-fold greater brightness and over 300-fold greater dynamic range than commercial quantum dots.
- IHC-PIDs demonstrated strong correlation (R=0.94) with FACS for total protein quantification.
- IHC-PIDs successfully categorized response to molecular target-based drug therapy in breast cancer patients.
Conclusions:
- IHC-PIDs offer a significant advancement in quantitative IHC, overcoming limitations of autofluorescence and enzyme activity.
- The PID particle number quantified by IHC-PIDs can serve as a predictive score for trastuzumab efficacy in breast cancer.
- This novel method holds promise for personalized medicine and improved pathological diagnostics.
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.
