The radiotracer can be visualized in vivo by using Positron Emission Tomography
Enzymes perform a range of key functions for the human body. As such, inside our cells, and inside the tiniest of organelles, proteins called cathepsins assist healthy cells with protein breakdown. However, in the presence of cancer cells spreading throughout the surrounding tissue, these enzymes can quickly turn on us, helping to promote tumor growth. Now, for the first time ever, scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) have developed a radiotracer they are using to track cathepsins on the surfaces of cancer cells. Through their experiments, the researchers were able to demonstrate that the substance they are using is preferentially taken up by diseased tissue.
It's a well-known fact that garbage is processed in recycling plants. Human cells, too, contain specialized recycling systems called lysosomes they use to break down old and damaged proteins into their component parts and process them, as well as proteins that have been taken up by our cells. Cathepsins figure prominently into this picture. Much like a pair of scissors, these enzymes are capable of unraveling proteins prior to the next steps in the recycling process. "Basically, these guys are like staff that work at our cells' recycling plants, where they perform an important job. Because when old or damaged proteins are not broken down, this may cause serious diseases," explains Dr. Reik Löser of the HZDR's Institute of Radiopharmaceutical Cancer Research.
However, this useful work can quickly turn sour the minute a tumor cell spreads to the extracellular matrix, the protein-rich material surrounding our cells. When this happens, cathepsins are released from lysosomes. Löser about the activity of tumor cell cathepsins within the extracellular matrix: "With their connection to their natural environment lost, these enzymes no longer remember they're actually recycling experts. Instead, they turn into something like overworked custodial staff at a museum, who can't decide whether it's art or trash they're looking at." In line with their regular job description, they end up furiously breaking down those proteins that give the tissue structure and stability, which in turn helps promote the spread of diseased cells.
"Which is why it's looking promising that we'll be able to treat tumors using inhibitory substances that help thwart the activity of cathepsins. In this context, it would be extremely helpful if we were able to visualize these enzymes with the help of medical imaging," says Löser. Using special chemical compounds called azadipeptide nitriles, the team around the Dresden researcher has come up with a radioactively labeled probe - a radiotracer - which binds to cancer cell cathepsins. "The basic substance is nothing more than an inhibitor to curtail the enzymes' molecular activities," explains Löser. "By attaching the radionuclide fluoride-18 to the chemical compound using a linker group, we managed to convert the substance into a radiotracer capable not only of detecting the tumor but also of telling us something about its propensity to invade the surrounding healthy tissue."
With the help of cutting-edge imaging technology called positron emission tomography (PET), the radiotracer - and, accordingly, the cathepsins plus the diseased cells - can be visualized in vivo. At a half-life of about 110 minutes, the tracer substance, which is injected into the bloodstream, disintegrates by the emission of positrons, which are positively charged, unstable elementary particles. As these positrons, too, "disappear," they give off additional energy - energy that can be measured using a detector. With the help of a computer, the measurements are then used to produce a three-dimensional image. The most intense radiation is given off by those cells containing the highest concentrations of deposits of the radioactively labeled substance. Says Löser: "This applies also to the tumor cells, as the tracer has a high affinity for binding to cathepsins on cancer cells."
The PET images help distinguish the healthy tissue from the diseased cells. The Dresden scientists were able to document this through experiments on mice that were carriers of human tumor cells. Their newly developed substance accumulated within the diseased cells. However, Löser is quite certain that it'll take time before the substance can be introduced into the clinical setting. "We have to increase the substance's stability in the bloodstream for a better contrast between tumor and healthy tissue. At this time, the contrast is still much too indistinct. Still, we have taken quite a giant leap forward with regards to development of a more precise way of diagnosing and characterizing tumors."
More news from this company
- Smart tomographic sensors control industrial processes of tomorrow (09/01/2017)
- Glutathione as a protective shield against Uranium (06/14/2016)
- Sustainable Processing of Rare Earths (04/01/2016)
- Novel concept for compact high-field high-repetition-rate accelerator-based Terahertz user facilities (03/15/2016)
- Camera for the Nano-Cosmos by combinin near-field optical microscopy and ultra-fast spectroscopy (08/17/2015)