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IBS Found a Fluorescent Material for Precision Diagnosis of Diabetes

  • Tuesday, February 25, 2020, 2:45 pm
  • ACROFAN=Seunghee Shin
  • seunghee.shin@acrofan.com
Techniques have been developed to quickly and accurately diagnose the development and progression of diabetes. The study was conducted by the Institute for Basic Science (IBS) research team led by Chang, Young-Tae (Professor, Department of Chemistry, Pohang University of Science and Technology) at the Center for Self-assembly and Complexity. They have developed a new PiF‧Pancreatic islet Fluorinated probe that can be used for both precision diagnosis and biopsy of diabetes through joint research at home and abroad.

The diagnosis of diabetes usually involves measuring the concentration of glucose in the blood (blood sugar). However, it is difficult to keep track of the disease progression with only blood sugar information in diabetes, which has a number of complex factors. If it becomes possible to directly measure the condition of the pancreatic beta cells responsible for insulin secretion, a more accurate diagnosis will be available.

▲ In vitro image after injecting PiF (Image by IBS)

Until now, the only way of the analysis was to remove some pancreas surgically. However, it was impossible to repeat the surgical method, and there was a limitation of finding all the pancreatic islets unevenly distributed in the pancreas and measure the amount quickly. In addition, it was also challenging to determine the number of beta cells varying with disease progression using an analysis technique that takes one to two days.

The research team has developed a tool for non-invasively visualizing beta cells and measuring the mass of healthy beta cells. They first selected compounds that fluoresce when they bind to insulin secreted from pancreatic beta cells. They then pre-introduced fluorine (F) atoms into candidate compounds for use as the contrast medium of positron emission tomography (PET), and finally sorted out PiF, which explicitly detects pancreatic beta cells.

Subsequently, the team injected PiF into the tails of type 1 diabetic mice that induced beta-cell destruction. As a result of an optical microscopic observation 2 hours after the injection, it was confirmed that PiF selectively detected only pancreatic beta cells. The treatment time was significantly reduced compared to the conventional biopsy, which required more complicated procedures and more than one day. As more insulin is bound, the fluorescence will get stronger, so based on the intensity of fluorescence, the amount of healthy pancreatic beta cells can also be identified.

▲ Fluorescence imaging using PiF after transplanting pancreatic islets (Image by IBS)

Diabetes patients who are unable to control their blood sugar levels receive treatment of transplanting pancreatic islets as a last resort. At the time, PiF can be used to monitor the success of transplantation. The research team transplanted 1000 separated pancreatic islets into mice's hepatic portal vein and injected PiF the next day. As a result, the PiF fluorescence signal of mice transplanted with pancreatic islets was significantly higher than that of mice without transplants. This means that based on the fluorescent signal, the transplanted pancreatic islet can be tested for proper fixation and function in the original tissue.

The research team confirmed the efficacy of PiF as a PET contrast medium through animal experiments. The fluorine atoms introduced into PiF were replaced with radioactive isotopes (fluorine-18) and then administered to mice. Isotopes differ only in the weight of their atoms, but their chemical properties are almost identical. Therefore, the features of PiF with high selectivity for beta cells are reflected in PET images.

PET analysis revealed a clear distribution of PiF in the pancreas. PiF reached the pancreas in 30 minutes and showed the highest absorption state, and most quickly escaped after 60 minutes. This means that when used as a contrast medium during diagnosis, the side effects are less likely to appear.

The findings were published on February 10 in the Journal of the American Chemical Society (IF 14.695).

▲ PET-CT images using PiF (Image by IBS)