lipflip – Metastatic melanoma, or stage IV melanoma, is a highly aggressive form of skin cancer that spreads to other organs. Traditional treatments like immunotherapy and targeted drugs have shown limited success, and conventional radiotherapy presents challenges due to its low energy transfer and potential harm to surrounding healthy tissues.
To address these limitations, a Japanese research team led by Assistant Professor Hiroyuki Suzuki from Chiba University has developed a new approach using targeted alpha therapy (TAT). Their breakthrough involves an astatine-211 (²¹¹At)-labeled peptide drug designed to enhance the effectiveness of radiotherapy while minimizing damage to healthy tissues.
This innovative treatment was developed in collaboration with experts from Chiba University, the National Institutes for Quantum Science and Technology, Juntendo University, and Osaka University. Their findings, published in the European Journal of Nuclear Medicine and Molecular Imaging on January 20, 2025. Highlight the potential of TAT to revolutionize metastatic melanoma treatment.
Targeted Alpha Therapy Shows Promise in Melanoma Treatment
Targeted alpha therapy (TAT) offers a new approach to radiotherapy by using drugs labeled with alpha particle-emitting radioisotopes. Unlike beta or gamma radiation, alpha particles have a short range but deliver high energy. Making them more effective at destroying cancer cells while reducing damage to surrounding healthy tissues.
A research team from Japan developed [²¹¹At]NpG-GGN4c, an astatine-211 (²¹¹At)-labeled α-melanocyte-stimulating hormone (α-MSH) peptide analog, to target melanocortin-1 receptors (MC1R), which melanoma cells overexpress. To improve tumor selectivity and minimize off-target effects, they first optimized a hydrophilic linker. The new compound demonstrated strong tumor specificity, reducing unnecessary radiation exposure to normal tissues.
Read More : Kim Sae-ron’s Death Exposes South Korea’s Celebrity Culture?
Testing Confirms Effectiveness in Melanoma Models
The team tested [²¹¹At]NpG-GGN4c on mice with B16F10 melanoma tumors. They analyzed biodistribution, tumor uptake, and clearance rates to assess treatment efficiency. Results showed high tumor accumulation and rapid clearance from non-target organs, confirming its specificity for MC1R.
Further studies revealed a dose-dependent suppression of tumor growth. Mice treated with the compound showed improved survival rates without significant toxicity. Additionally, the peptide demonstrated high stability in blood plasma, minimizing the risk of radioactive leakage. These findings suggest that [²¹¹At]NpG-GGN4c could be a breakthrough in metastatic melanoma treatment. Offering a more precise and effective alternative to conventional radiotherapy.
Potential for Expanding Targeted Alpha Therapy to Other Cancers
Dr. Suzuki and his team strongly believe that their molecular design for the astatine-211 (²¹¹At)-labeled drug could, in turn, pave the way for developing additional radiopharmaceuticals. Moreover, their approach effectively demonstrates how targeted alpha therapy (TAT) can be further adapted to treat other difficult-to-treat cancers beyond melanoma. By continuously refining the process, researchers could eventually expand the application of ²¹¹At-based treatments to a much broader range of malignancies.
The team is optimistic about advancing this therapy toward clinical trials. If successful, this targeted treatment could offer new hope for patients with advanced melanoma and other refractory cancers. Dr. Suzuki anticipates that with further research and regulatory approvals, ²¹¹At-based therapies may soon become viable options for individuals with limited treatment alternatives, significantly improving patient outcomes.