KONICA MINOLTA

About Konica Minolta

Giving Shape to Ideas

Technologies for the Future

FLUORESCENT
NANOIMAGING

IMMUNOSTAINING TECHNOLOGY
THAT WILL REVOLUTIONIZE
CANCER TREATMENT
+ ANALYSIS TECHNOLOGY

Background
Pinpointing cancer cells
The era of
personalized medicine

With a growing elderly population worldwide, the number of cancer patients is also increasing.
According to a study by the International Agency for Research on Cancer (IARC), a branch of the World Health Organization(WHO), approximately 14.1 million new cases were reported in 2012; a number expected to rise by 150% to 21.6 million by 2030.
While advances in medical science have made cancer more treatable than ever, approximately 8.2 million people died of cancer worldwide in 2012, making it the #1 deadly disease and a major issue for society.

Pharmaceutical companies are working hard to develop cancer drugs. One recent focus has been on what are called "molecularly-targeted drugs" aimed at specific types of cancer. These drugs attack cancer cells with pinpoint accuracy, making them a highly effective form of treatment.
However, accurate diagnostic pathology is essential to developing and using these drugs. When someone has or is suspected of having cancer, accurately determining the amount and location of certain proteins in a tissue sample from that person allows for the development and deployment of an appropriate molecularly-targeted drugs at an early stage. Cancer becomes more "treatable" than ever.

With this in mind, Konica Minolta and Tohoku University have developed High Sensitive Tissue Testing (HSTT), which accurately detects the proteins that manifest in cancer cells using fluorescent nanoparticles.* HSTT determines the location and amount of specific proteins that manifest in cancer cells, offering an early-stage, highly precise diagnosis. It will also allow for better grouping of cancer patients, increase success rates of clinical trials, generate economic benefits for the healthcare industry, and improve cure rates of cancer.

*In the development of this technology, we received support between 2010 and 2014 from Research and Development Project to develop technology and system for highly precise diagnosis of tumor tissues by single-particle fluorescence imaging, part of the Integrated Project for Research and Development to develop extremely-early diagnosis and treatment devices for cancer by NEDO. We researched and developed this project with Professors Noriaki Ouchi and Kosuke Gonda of the Tohoku University School of Medicine, (Faculties of Medical Science and Nano-medical Science), as well as a group at the Tohoku University Hospital (Department of Pathology).

Technology
UNIQUE FLUORESCENT NANOPARTICLES
FOR ACCURATE
CANCER TREATMENT

Typically in a pathological examination, the doctor takes a tissue sample from the patient through an endoscopy or surgery. The sample is then placed on a slide, and dyed so it can be easily seen; a process known as immunostaining. Immunostaining allows doctors to check for the presence of specific proteins, and determine how far the cancer has spread.
Using the DAB method, a conventional compound for immunostaining, it is possible to confirm whether or not particular proteins found in cancer cells are present. With Konica Minolta's HSTT, we can not just confirm the presence of these proteins, but also their amount and location.

Only the specific proteins are illuminated. (nanostaining)
PID IMAGING + ANTIGEN-ANTIBODY INTERACTION CONTROL

With older forms of immunostaining, it was difficult to detect proteins quantitatively or with a high degree of precision.
Staining with enzymes creates a photochemical reaction which makes it impossible to determine the exact number of cells.
Regular fluorescent substances are not bright or sensitive enough, meaning images come out uneven.

HSTT uses fluorescent nanoparticles developed by Konica Minolta called Phosphor Integrated Dots (PIDs), which make it possible to pinpoint the amount and location of proteins that manifest in cancer cells. PIDs are tiny particles, just dozens of nanometers long, made of highly sensitive and resilient substances, and are extremely bright. Roughly 10,000 times brighter than a typical fluorescent substance, and highly durable. Even if there are only a small amount of cancer cell proteins present, the luminescent PIDs will stand out clearly.

It is crucial that the PIDs attach to the specified proteins (antigens), and as few other particles as possible. In HSTT, we use methods that increase the chances the PIDs will attach to the right proteins including exposing tissue samples to two stages of antigens. In addition, we give the PIDs a surface treatment and a unique blocking substance to decrease the chances they will adhere to other particles. All of this means that only the specified proteins will be dyed.

Pattern recognition algorithms
determine the number
and location of proteins

SOFTWARE ANALYSIS

PIDs light up diseased tissue to enable accurate count and positioning of cancer cell proteins in tissue samples. This is captured using a fluorescence microscope, and then analyzed using specialized software.

Images of the tissue are digitized. Then, "cell nucleus analysis module" and "light spot analysis module” algorithms are employed. The cell nucleus module determines the location and area of the cells, while the light spot module counts each point of light it sees as a PID. The higher the numbers, the more PIDs/cancer cell proteins there are. By analyzing each measured value, it is possible to determine which kinds of cells are where, and how much of which proteins are present.

Because different proteins manifest in different kinds of cancer cells, this technology can determine which kind of cancer is present and what the best treatment options are.

Solution
ACCURATE CLASSIFICATION OF PATIENTS
MEANS ADVANCES IN NEW DRUGS
AND PERSONALIZED MEDICINE

In July 2015, Konica Minolta began a "pathology specimen production" program, in an effort to put HSTT technology to practical use. Specimens were collected from companies in the healthcare industry, analyzed using our nanostaining technology, and then the data was published. Our hope is that this data will be used by pharmaceutical companies to develop new drugs. For example, in the development of molecularly-targeted drugs. In clinical trials, it's essential to know if the treatment is working for a given patient or not. Without that, it’s difficult to prove that the treatment works in the first place. HSTT makes it possible to reliably classify patients. Knowing which proteins, and therefore which cancers, are present, means knowing whether molecular targeting should work or not. Clinical trials can move forward quickly and effectively, saving time and money and hastening successful development of new drugs.

We hope this will make a contribution in cancer diagnosis and treatment. By being able to detect smaller amounts of cancer cell proteins than ever before, the right treatment course can be chosen early. This will not just lead to "personalized medicine," (where treatments are tailored to each patient and form of cancer,) it will also decrease unnecessary treatments, ensuring medical resources and services are allocated efficiently and effectively.

Future
DIGITIZATION LEADS TO
MORE EFFICIENT DIAGNOSIS
AND MOLECULAR IMAGING

Today, our main aim for HSTT is for it to support the diagnosis of disease through the analysis of specimens, but we are also exploring future applications. For example, "digital pathology," would allow diagnostic pathology to be done remotely, saving time and money. Or technology that would allow tissue to be analyzed inside the body without being extracted, making things easier on the patient.
When HSTT can be used effectively in molecular imaging, we would also be able to observe how drugs initially move through the body (such as where they are carried, and if they are having an effect).
Konica Minolta is eager to continue finding uses for its unique fluorescent nanoimaging PID technology, whether to help develop new treatments, cut healthcare costs, or improve patients' survival rates and quality of life, we hope to continue making a contribution to solving the world's challenges.

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