Targeted Alpha Therapy (TAT)

Targeted Alpha Therapy (TAT) is an advanced form of cancer treatment that uses alpha-emitting radionuclides attached to targeting molecules (such as antibodies, peptides, or small molecules) that specifically bind to cancer cells.

1. A targeting vector (e.g., a monoclonal antibody) is linked to an alpha-emitting radionuclide.
2. This compound is administered to the patient and selectively binds to tumor-specific antigens on the surface of cancer cells.
3. The alpha particles, which have high energy but short range (~50–100 micrometers), are emitted at the tumor site.
4. These particles cause double-strand DNA breaks, leading to irreversible damage and cell death, primarily in the targeted cancer cells.

• High cytotoxicity – Effective even in small numbers.
• Minimal off-target effects – Due to short range of alpha particles.
• Effective against micrometastases and isolated cancer cells.

• Actinium-225 (²²⁵Ac)
• Astatine-211 (²¹¹At)
• Bismuth-213 (²¹³Bi)
• Thorium-227 (²²⁷Th)

• Prostate cancer (e.g., 225Ac-PSMA-617)
• Leukemia and lymphoma
• Gliomas
• Neuroendocrine tumors

1. Limited supply of suitable alpha emitters
2. Radiochemistry complexity
3. Toxicity management, especially renal and bone marrow
4. Cost and regulatory hurdles

Glioblastoma Targeted Alpha Therapy