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Alpha particle: New approach to treating many types of cancer
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Alpha particle: New approach to treating many types of cancer.
Researchers led by Katsunori Tanaka of the RIKEN Pioneering Research (CPR) Cluster in Japan and Hiromitsu Haba of RIKEN Nishina Accelerator Science Center (RNC) in RIKEN have developed a new technique that has the potential to universally treat a variety of cancers, unlike currently available method with fewer side effects.
Image source: RIKEN
The proof-of-concept study, published June 27 in the journal Chemical Science, showed that tumor growth in mice was nearly three-fold reduced and 100 percent survivable after injecting just one compound, Designed to emit small amounts of alpha radiation. inside the cancer cells, killing them without harming healthy tissue.
The side effects of standard chemotherapy and radiation can be devastating, and there is no guarantee that all cancer cells will be wiped out, especially if the cancer has metastasized and spread throughout the body.
Therefore, the goal of most current research is to find a way to specifically target cancer cells so that the treatment affects only the tumor.
Some targeted therapies do exist, but they do not work for all cancers.
“One of the greatest strengths of our new method is that it can be used to treat a variety of cancers without any targeting vectors such as antibodies or peptides,” Tanaka said.
Targeted alpha particle therapy (TAT) using 211At radiolabeled 2,6-diisopropylphenyl azide (ADIPA). Image source: RIKEN
The new technique relies on basic chemistry and the fact that a compound called acrolein accumulates in cancer cells. A few years ago, Tanaka’s group used a similar technique to detect individual breast cancer cells.
They attached a fluorescent compound to a specific type of azide, an organic molecule with three nitrogen atoms (N3) at the end. When the azide and acrolein meet inside the cancer cell, they react and the fluorescent compound anchors to the structure inside the cancer cell.
Since acrolein is almost absent in healthy cells, the technique acts like a probe to illuminate cancer cells in the body.
In the new study, instead of simply detecting cancer cells, the team targeted those cells for destruction.
The logic is fairly simple. Instead of attaching the azide to a fluorescent compound, they attached it to a substance that would kill the cells without harming surrounding cells. They chose to use astatine-211, a radionuclide that emits small amounts of radiation in the form of alpha particles when it decays.
Alpha particles are somewhat more deadly than other forms of radiation therapy, but they only travel about one-twentieth of a millimeter and can be stopped by a piece of paper. In theory, when astatine 211 is anchored inside a cancer cell, the emitted alpha particles can damage the cancer cell without causing too much tissue damage.
Once the team figured out the best way to attach astatine 211 to the azide probe, they were able to conduct a proof-of-concept experiment to test their theory.
They implanted human lung tumor cells into mice and tested the treatment under three conditions: simply injecting astatine 211 into the tumor, injecting an astatine 211 azide probe into the tumor, and injecting astatine 211 azide into the tumor.
Compound probes are injected into the bloodstream. They found that without targeting, the tumors continued to grow and the mice did not survive. As expected, when the azide probe was used, the tumor growth rate was almost threefold reduced and more mice survived—100% survival when injected into the tumor and 100% when injected into the bloodstream. The survival rate is 80%.
“We found that just one tumor injection containing only 70 kBq of radioactivity can target and eliminate tumor cells very effectively,” Tanaka said. “We were able to achieve similar results even when the therapeutic compound was injected into the bloodstream.” This means we can use this approach to treat very early-stage cancers even if we don’t know where the tumors are.”
A fluorescent probe version of the technology is already being tested in clinical trials as a way to visualize/diagnose cancer at the cellular level, the next step is to find partners and start clinical trials using this new approach to treat cancer in humans .
Image source: RIKEN
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