The "Goldilocks" Isotope for Cancer Therapy

At-211 is often called the "perfect" or "Goldilocks" isotope because it can deliver just the right amount of radiation to destroy cancer cells while leaving the surrounding tissue unharmed. This breakthrough isotope has demonstrated strong potential against blood cancers, ovarian tumors, and certain brain cancers. Within the Texas A&M Cyclotron Institute, scientists are producing At-211 using the K150 cyclotron with support from the U.S. Department of Energy (DOE) Isotope Program. Since 2023, Texas A&M has been one of only two national suppliers of astatine for targeted cancer therapy through the National Isotope Development Center (NIDC) and its University Isotope Network.

"Targeted alpha therapy is a potentially transformative cancer therapeutic of great interest due to its ability to cause large amounts of damage near a tumor cell while keeping the healthy surrounding tissue and organs intact," said Texas A&M Distinguished Professor and Regents Professor of Chemistry Dr. Sherry J. Yennello, director of the Cyclotron Institute. "We are one of a handful of U.S. centers capable of routinely producing astatine in medically relevant quantities and delivering it to nearby facilities."

Harnessing the Power of Alpha Particles

When astatine decays, it emits alpha particles -- tiny clusters made of two protons and two neutrons -- that can release powerful, localized bursts of energy. These alpha particles are highly effective in destroying cancer cells because they travel only a short distance before releasing their energy, minimizing damage to healthy tissue. When At-211 is positioned within or near tumors, its alpha emissions penetrate just deep enough to eliminate cancerous cells while sparing surrounding organs.

At-211's short half-life also means it quickly loses its radioactivity, making it less toxic than longer-lived radiopharmaceuticals. Unlike many other isotopes, At-211 does not produce harmful secondary alpha decay, ensuring that its energy is used efficiently for therapy. This combination of precision and safety has drawn attention from researchers and pharmaceutical developers worldwide. It is already being tested in clinical trials for blood cancers and explored for potential use in treating Alzheimer's disease.

"Astatine-211's availability remains the biggest hurdle to harnessing its potential to transform the future of nuclear medicine," Yennello said. "Fortunately, the advances we're making here at Texas A&M will go a long way toward addressing that."

A Breakthrough in Isotope Production and Transport

One of Texas A&M's major achievements has been the creation of an automated system to separate and ship At-211. This patent-pending technology purifies the isotope by removing it from the bismuth target and then loads it onto a shipping column for incorporation into targeted alpha therapy drugs. According to Yennello, the new resin-column trapping technique allows for faster processing, enabling larger quantities of At-211 to be shipped with minimal decay and reduced risk compared with traditional methods. This improvement strengthens the case for At-211 as a viable next-generation cancer treatment.

Texas A&M has already delivered significant batches of At-211 to collaborators, including the University of Alabama at Birmingham and MD Anderson Cancer Center, which has received more than two dozen shipments. These partnerships are helping researchers refine At-211-based radiopharmaceuticals and deepen understanding of its chemical behavior.

Collaboration and Global Progress

Yennello and Dr. Federica Pisaneschi, a former MD Anderson radiochemist now at the University of Texas Health Science Center at Houston, are scheduled to present their findings at the 2025 World Astatine Community Meeting in New Orleans. Their talk, titled "The Texas Two-Step," will highlight their combined experience producing, shipping, and applying At-211 for therapeutic use. This first U.S.-based meeting will bring together researchers and commercial groups dedicated to expanding At-211's role in cancer treatment worldwide.

Yennello recently shared Texas A&M's progress at another major event -- the 26th International Symposium on Radiopharmaceutical Sciences, held in Queensland -- where she emphasized growing international interest in At-211 research.

"Although clinical trials in humans are in the early stages, there are initiatives currently looking at astatine-211's potential in Japan, several European countries and the United States," Yennello said. "I'm looking forward to sharing Texas A&M's success in producing and supplying astatine-211 while also learning more about global progress in our common efforts to better understand its chemical properties and possible therapeutic advancement in oncology."

This pioneering research is supported by the DOE Office of Science through the DOE Isotope Program, by Texas A&M through the Bright Chair in Nuclear Science, and by The Texas A&M University System Nuclear Security Office in partnership with Los Alamos National Laboratory.

In most cases, the cancer disappeared within three months of therapy, and nearly half of the patients remained cancer-free one year later.

"Traditionally, these patients have had very limited treatment options. This new therapy is the most effective one reported to date for the most common form of bladder cancer," said Sia Daneshmand, MD, director of urologic oncology at Keck Medicine of USC and lead author of the study, which was published in the Journal of Clinical Oncology. "The findings of the clinical trial are a breakthrough in how certain types of bladder cancer might be treated, leading to improved outcomes and saved lives.

How the TAR-200 System Works

The TAR-200 device is a small, pretzel-shaped implant that holds the chemotherapy drug gemcitabine. It is inserted into the bladder using a catheter, where it gradually releases the drug over the course of three weeks in each treatment cycle.

Traditionally, gemcitabine has been delivered as a liquid solution that remains in the bladder for only a few hours, which limited its effectiveness in killing cancer cells, said Daneshmand, who is also a member of the USC Norris Comprehensive Cancer Center.

"The theory behind this study was that the longer the medicine sits inside the bladder, the more deeply it would penetrate the bladder and the more cancer it would destroy," he explained. "And it appears that having the chemotherapy released slowly over weeks rather than in just a few hours is a much more effective approach."

Details of the Global Clinical Trial

The study, called SunRISe-1, took place at 144 sites around the world, including Keck Hospital of USC. It enrolled 85 patients diagnosed with high-risk non-muscle-invasive bladder cancer.

This form of cancer is the most common type of bladder cancer. It is classified as high risk when tumors are more likely to recur or spread into the bladder's muscle layer or to other areas of the body.

Standard Treatments and the Need for New Options

Patients in the trial had previously been treated with Bacillus Calmette-Guérin (BCG), an immunotherapy drug that is the current standard of care. However, for a portion of patients, BCG is ineffective and the cancer returns.

"The standard treatment plan for these patients was surgery to remove the bladder and surrounding tissue and organs, which has many health risks and may negatively impact patients' quality of life," said Daneshmand.

Strong Results with Fewer Side Effects

To provide a safer alternative, doctors administered TAR-200 every three weeks for six months, followed by four treatments per year for the next two years. Out of 85 patients, 70 experienced complete tumor disappearance, and nearly half remained cancer-free after one year. The therapy was well tolerated, with minimal side effects reported.

Researchers also found that combining TAR-200 with another immunotherapy drug (cetrelimab) was less effective and caused more side effects than TAR-200 alone.

Participants in the study will continue to be monitored for another year, but enrollment is now closed.

The Promise of Slow-Release Cancer Therapies

This study is part of a growing wave of research exploring slow-release drug delivery systems for cancer treatment. These approaches aim to provide longer-lasting exposure to cancer-fighting drugs directly at the tumor site.

"We are at an exciting moment in history," said Daneshmand, who has been investigating this technology since 2016. "Our mission is to deliver cancer-fighting medications into the bladder that will offer lasting remission from cancer, and it looks like we are well on our way toward that goal."

The U.S. Food and Drug Administration has granted TAR-200 a New Drug Application Priority Review, which allows the agency to expedite its evaluation. The device is manufactured by Johnson & Johnson.

Disclosure: Daneshmand has received grants/research funding and travel reimbursement from Johnson & Johnson, as well as consulting payments from Johnson & Johnson Innovative Medicine (formerly Janssen Pharmaceuticals).