Breakthrough Cancer Treatment: Japan’s Alpha Particle Assassin

Researchers at Japan’s RIKEN institute have made a significant breakthrough in cancer treatment with a revolutionary technique that selectively kills cancer cells using alpha radiation, while sparing healthy tissue. This groundbreaking approach, successfully tested on mice, resulted in a remarkable 100% survival rate and substantial reduction in tumor growth. By leveraging the cancer cells’ affinity for the compound acrolein, the scientists introduced a molecule called astatine-211, which emits alpha radiation upon decay. With plans to advance to clinical trials in humans, this development holds immense potential for treating multiple types of cancer.

Led by Katsunori Tanaka from the RIKEN Cluster for Pioneering Research (CPR) and Hiromitsu Haba from the RIKEN Nishina Center for Accelerator-Based Science (RNC), the team has devised a technique that offers a generic approach to treating various cancers with fewer adverse side effects compared to existing methods. Their proof-of-concept study, published on June 27 in the journal Chemical Science, revealed that a single injection of a compound designed to emit controlled amounts of alpha radiation within cancer cells achieved nearly three times less tumor growth in mice and a 100% survival rate, while leaving healthy tissue unharmed.

Standard chemotherapy and radiation treatments often come with devastating side effects, and the complete eradication of cancer cells is not guaranteed, particularly in cases where the cancer has metastasized. Consequently, current research aims to identify targeted treatments that selectively attack tumors, sparing healthy cells. Although some targeted treatments are available, they are not universally applicable to all types of cancer. Tanaka explains, “One of the greatest advantages of our new method is that it can be used to treat many kinds of cancer without any targeting vectors, such as antibodies or peptides.”

The technique builds on basic chemistry and exploits the accumulation of a compound called acrolein in cancer cells. Previously, Tanaka’s team employed a similar approach to detect individual breast cancer cells, using a fluorescent compound attached to a specific type of azide—a molecule featuring a group of three nitrogen atoms (N3) at the end. When the azide and acrolein interact within a cancer cell, they form a reaction that anchors the fluorescent compound to internal structures within the cell. This technique acted as a probe, illuminating cancer cells within the body since acrolein is nearly absent in healthy cells.

In their latest study, the researchers went beyond detection and targeted cancer cells for destruction. They modified the approach by attaching the azide to a substance capable of killing cells without harming neighboring healthy cells. The team chose to work with astatine-211, a radionuclide that emits a small amount of radiation in the form of alpha particles upon decay. Although alpha particles are highly lethal, they have a limited travel distance of about one-twentieth of a millimeter and can be stopped by a piece of paper. In theory, when astatine-211 is anchored to the inside of a cancer cell, the emitted alpha particles should exclusively damage the cancer cell and minimize harm to surrounding tissue.

Once the optimal method of attaching astatine-211 to the azide probe was determined, the researchers conducted a proof-of-concept experiment to test their hypothesis. They implanted human lung tumor cells into mice and subjected them to three different conditions: injection of astatine-211 directly into the tumor, injection of the astatine-211-azide probe into the tumor, and injection of the astatine-211-azide probe into the bloodstream. The results were consistent with expectations: without targeting, tumors continued to grow, and mice did not survive. However, when the azide probe was used, tumor growth decreased by almost threefold, and a significantly higher number of mice survived—100% when injected into the tumor and 80% when injected into the bloodstream.

Tanaka states, “We found that a single tumor injection with just 70 kBq of radioactivity was highly effective at targeting and eliminating tumor cells. Even when administering the treatment compound into the bloodstream, we achieved similar results. This means we can use this method to treat very early-stage cancer, even without precise knowledge of the tumor’s location.”

The fluorescent probe version of this technique is already undergoing clinical trials to visualize and diagnose cancer at the cellular level. The next phase involves partnering with institutions to initiate clinical trials utilizing this groundbreaking method for cancer treatment in humans.

Reference: “Therapeutic efficacy of 211At-radiolabeled 2,6-diisopropylphenyl azide in mouse models of human lung cancer” by Yudai Ode, Ambara R. Pradipta, Peni Ahmadi, Akihiro Ishiwata, Akiko Nakamura, Yasuko Egawa, Yuriko Kusakari, Kyohei Muguruma, Yang Wang, Xiaojie Yin, Nozomi Sato, Hiromitsu Haba, and Katsunori Tanaka, 27 June 2023, Chemical Science.
DOI: 10.1039/D3SC02513F

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• RIKEN Institute: Official Website
• Chemical Science Journal: Research Publication
• ClinicalTrials.gov: Clinical Trials Database
• American Cancer Society: Cancer Treatment Information