March 13, 2026
As part of a multisite, international clinical trial, Mayo Clinic is the first organization in the U.S. to treat a patient with a new radiopharmaceutical drug to target metastatic breast cancer. The clinical trial investigates actinium-225 DOTATATE, a highly potent alpha-emitting radiopharmaceutical therapy, for the treatment of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.
"This treatment is the first of its kind for metastatic breast cancer, and it targets the most common subset," says Rohit R. Rao, M.B.B.S., M.D., a medical oncologist at Mayo Clinic in Florida and co-investigator of the clinical trial. "Our hope is that radiopharmaceutical therapy will offer a benefit to our patients when other treatments haven't been helpful."
The phase 1b/2 open-label trial is underway at the Mayo Clinic academic sites in Minnesota, Arizona, and Florida and will roll out at approximately 20 other sites across the U.S. The first patient was treated with actinium-225 DOTATATE at Mayo Clinic in Florida.
Radiopharmaceutical therapy
Geoffrey Johnson, M.D., Ph.D., is a nuclear medicine specialist and a professor of radiology at Mayo Clinic in Rochester, Minnesota, and principal investigator of the trial. He explains that theranostics and radiopharmaceutical therapies deliver radioactive medicines designed to target and kill cancer cells with a high level of precision. The radiopharmaceutical is injected into a patient's vein and then finds and sticks to specific cancer cells to deliver powerful and targeted radiation from within tumors without harming the surrounding, healthy cells.
Actinium-225 DOTATATE was first developed to treat a rare subtype of gastroenteropancreatic neuroendocrine tumor. While the radiopharmaceutical is not Food and Drug Administration (FDA) approved in the U.S., it is currently under evaluation in the last part of a phase 3 trial for gastroenteropancreatic neuroendocrine tumors and a phase 1 trial for lung cancer. Dr. Johnson says early data indicate that the therapy is well tolerated.
"Actinium-225 DOTATATE is distinct because unlike most other radiopharmaceuticals we have used, it's an alpha emitter," says Dr. Johnson. "It's incredibly precise and works only right where the molecule is."
On average, the radiation of alpha-emitting radiopharmaceuticals travels just three cell lengths, whereas that from beta-emitting radiopharmaceuticals travels thousands of cell lengths and offers a lower level of precision. In addition, the alpha particles emitted are 8,000 times larger than beta particles. However, currently only beta-emitting therapies attached to DOTATATE are approved by the FDA.
In preclinical studies, data indicate that actinium-225 DOTATATE demonstrated feasibility and potential efficacy for the treatment of ER+ metastatic breast cancer in the laboratory by targeting somatostatin receptor subtype 2 expression. The radiopharmaceutical was developed by RayzeBio Inc., the sponsor of the active phase 1b/2 clinical trial.
Criteria for trial participation
To participate in the trial, patients must have histologically confirmed ER+, HER2-negative metastatic breast cancer, as well as previous treatment with two to four lines of chemotherapy and one round of antibody-drug conjugates (ACDs). In addition, 80% of measurable tumors must be somatostatin receptor (SSTR) positive on a DOTATATE PET scan to ensure that they express the target actinium-225 DOTATATE for binding. An estimated 1 in 3 to 1 in 5 patients has the markers required to participate in the study and receive the therapy, which is given over several months.
"We are actively searching for novel therapies and treatment options that are well tolerated and help maintain our patients' quality of life," says Dr. Rao. "This potent treatment is so targeted that side effects should be minimal, which is a great benefit for our patients."
Additional Mayo Clinic research on radiopharmaceuticals
Mayo Clinic has more than 20 active clinical trials in progress to study radiopharmaceutical therapies and their effects on different types of cancer, with additional trials preparing to launch soon.
As a leader in the use of radiopharmaceuticals, Mayo Clinic in Minnesota treats more patients with radiopharmaceuticals, including lutetium-177 DOTATATE and lutetium-177 PSMA, than any other medical center in the world. Lutetium-177 DOTATATE, which is used to treat neuroendocrine cancers, and lutetium-177 PSMA, which targets prostate cancers, are both beta-emitting radiopharmaceuticals.
For more information
RayzeBio Inc. Trial of 225Ac-DOTATATE (RYZ101) in Subjects with ER+, HER2-Negative Unresectable or Metastatic Breast Cancer Expressing SSTRs. (TRACY-1). ClinicalTrials.gov.
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