QST develops drug that enables both diagnosis and treatment simply by swapping radionuclides — Single dose suppresses tumor growth in both primary and metastatic lesions

Director Ming-Rong Zhang, Principal Researcher Lin Xie, and their colleagues from the Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST) have announced the successful development of a theranostic drug targeting metabotropic glutamate receptor 1 (mGluR1) present on the surface of cancer cells. This new medical technology integrates therapy and diagnosis, allowing prediction of treatment efficacy before therapy begins, while alpha and beta rays physically destroy cancer cells with powerful energy. The drug is expected to enable potent and safe personalized medicine across a wide range of cancer types. The findings were published in Molecular Therapy on March 11.

Theranostics is a new medical technology that integrates therapy and diagnosis. In radiotheranostics, its application in the field of nuclear medicine, imaging is performed using a diagnostic agent that combines antibodies or drugs (molecularly targeted drugs)-which accumulate at molecules on the surface of cancer cells-with gamma-ray radionuclides or positron emission tomography (PET) radionuclides. The radionuclide attached to the drug is then replaced with an alpha-emitting or beta-emitting radionuclide to carry out treatment.

PET is a diagnostic method in which a drug is administered to the subject, and gamma rays arising from positrons emitted by the drug are detected to image the distribution and quantity of biological substances in deep tissue. Because this can confirm the state of the cancer and the amount of drug accumulation, it enables prediction of treatment efficacy before therapy begins.

Alpha and beta rays damage the DNA of cancer cells with powerful energy, killing them. By enabling both of these functions with the same drug, the team has developed a paired agent comprising the PET diagnostic agent "¹¹C-IMTM" and the targeted alpha-particle therapy (TAT) drug "²¹¹At-AMTM," allowing both diagnosis and treatment to be performed.

When the drug was administered to a mouse model with subcutaneously transplanted mouse-derived malignant melanoma and PET imaging was performed, the drug accumulated at high levels in the tumor site, confirming its usefulness for diagnosis. Accumulation in the brain and blood, which is associated with toxicity to the body, was low, and no safety concerns were identified.

Next, when ²¹¹At-AMTM was administered to mice, tumor growth was suppressed in all individuals, and the effect lasted for 10 days. Targeted alpha-particle therapy drugs are anticipated to be effective not only against primary lesions but also against metastases.

A lung metastasis mouse model was then created and evaluated. PET imaging clearly visualized the metastatic lesions in the lung, and survival was approximately doubled. Furthermore, evaluation in pancreatic cancer, which is refractory cancer, demonstrated a marked tumor growth suppression effect, with complete tumor elimination observed in 7 of 15 animals.

Astatine (At), which is used in the therapeutic drug, is a halogen element that can be produced by a cyclotron accelerator, making it relatively inexpensive and suitable for domestic production. Therapeutic effects have been confirmed even with a single administration, and the burden on the body is low. The team aims to proceed to clinical trials in humans in the future.

Journal Information
Publication: Molecular Therapy
Title: A mGluR1-targeted radiotheranostic strategy visualizes lesions and potentiates antitumor efficacy in melanoma and pancreatic cancer
DOI: 10.1016/j.ymthe.2026.02.032