High Sensitive Tissue Testing
A diagnostic technique using nanotechnology could promote cancer treatment and the hunt for new drugs
By 2030, more than 21 million people annually will hear the words “you have cancer” from a doctor. This is nearly double the figure for 2008, according to the American Cancer Society, and means that now, more than ever, we need effective diagnostic techniques and treatments to keep the disease in check.
Cancer is a widespread, complex disease that has long defied easy, effective treatment. Conventional treatments such as chemotherapy use chemicals to attack cancer cells, but they also damage healthy cells, causing hair loss, a weakened immune system and digestive tract inflammation.
Over the past 20 years, doctors around the world have been trying to fight cancer with approaches that target the disease at the molecular level. If a drug can be delivered only to proteins in cancerous cells, patients could experience fewer side effects, easing recovery. One example is monoclonal antibodies which target a specific protein on cancer cells: mortality rates from non-Hodgkin lymphoma have dropped in the USA since monoclonal antibody drugs were introduced in 1997.
A key part of this strategy involves examining tissue samples to determine which proteins are present so doctors can deploy the right drugs for the cancer in question. A technique called immunostaining has traditionally relied on an organic compound, which allows pathologists to confirm whether cancer cell proteins are present in a sample, showing how far the disease has spread.
But a new approach developed by Konica Minolta allows for a more accurate picture of cancer’s progression — it shows not only whether cancer is present, but the location and number of cancer proteins.
The technique, developed in cooperation with professors Noriaki Ohuchi and Kohsuke Gonda of Tohoku University, is called High Sensitive Tissue Testing (HSTT) and it’s based in part on Konica Minolta’s photography know-how cultivated over a century.
The light-sensitive chemicals used in photographic film, known as silver halide particles, are the building blocks for making extremely small particles called Phosphor Integrated Dots (PIDs).
Measuring only a few dozen nanometers across, PIDs are fluorescent nanoparticles conjugated with antibodies that act as hooks. After the tissue samples and PIDs are optimized, the antibodies will only hook onto antigens on proteins on the targeted cancer cells.
Since the PIDs are 30,000-fold brighter than conventional fluorescent substances, they stand out clearly in tissue samples when irradiated, acting like tiny points of light. When they’re imaged with a fluorescence microscope and processed using specialized software, the result is a digital map and numerical count of cancer cells. Statistical software can process this information and determine the type of cancer present and the best course of treatment.
“Unlike conventional approaches, the location and strength of protein expression can be seen via digital means and with high sensitivity in HSTT,” says Hiroaki Yanagimoto, assistant professor of surgery at Kansai Medical University. “In addition, through multiple immunostainings, we can grasp the positional relationship of lymphocytes and other objects. This can lead to better decisions and therapeutic effects. It’s hoped that this will lead to big breakthroughs in cancer treatment.”
While there’s still a long way to go, the HSTT method has the potential to revolutionize cancer diagnosis and therapy. Effective treatments could be launched with early diagnosis and patients would benefit from personalized strategies.
Konica Minolta is now working with pharmaceutical companies to prove the efficacy of HSTT through clinical trials.
HSTT could be evolved into an even more sophisticated tool by applying it not only to tissue samples, but to cells inside the body itself.
Konica Minolta is developing an observation system to track PIDs in mice in a joint research project with France’s Institut Pasteur and imaging startup BioAxial, with funding from the Japan-France Bilateral R&D Cooperation Program, as part of Japan’s New Energy and Industrial Technology Development Organization (NEDO). It allows researchers to see how the drug with PIDs affects target cells, potentially accelerating the process of drug discovery. This invitro observation on the nanoscale presents a big business opportunity in drug testing.
“We’re providing this technology to drug discovery and clinical trial programs, but ultimately we would like to develop a testing and diagnostic business for functional contrast agents and induced pluripotent cells,” says Kunihiro Koshizuka, senior executive officer at Konica Minolta.
Konica Minolta is developing HSTT so it can work with material such as DNA so that a diagnosis could be made based on a simple blood test. In the future, quantitative protein data could be combined with other medical information to produce more advanced diagnostic results, says Koshizuka.
Konica Minolta has been working with hospitals and pharmaceutical companies to improve our workflow in everything from document handling to document management.
HSTT, however, is one example our ongoing transformation into what we call Cyber Physical Systems — the capturing and processing of huge amounts of data based on observed events in the real world. In the case of HSTT, Konica Minolta won’t sell the equipment or even the PIDs for cellular cancer testing. Instead, we will provide the service of measuring the protein quantities and diagnostic results.
“We want to help society through diagnosis and drug discovery,” says Koshizuka. “So we’re building on our legacy know-how of fine chemicals and particle synthesis from analog photography technology, and combining that with deep learning and protein visualization to unleash the potential of HSTT. We believe this could have a tremendous impact on healthcare.”
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