The metastatic melanoma is also called stage IV melanoma. It’s a form of skin cancer which spreads into other areas of the body. Current therapies, including targeted drugs and immunotherapy, are only partially effective. The use of radiotherapy to treat melanoma is a new treatment. However, conventional beta-emitting therapies are limited by their long range radiation and low energy transfer. This can result in unintended tissue damage. A research team led by Professor Hiroyuki Suzuki of Chiba University and including Dr. Tomoya UEhara, Chiba University and Dr. Noriko SS Ishioka, National Institutes for Quantum Science and Technology and Dr. Hiroshi TANAK from Juntendo University and Dr. Tadashi WATABE from Osaka University adopted the targeted alpha treatment (TAT) to enhance radiotherapy efficacy. The team developed a astatine-211-labeled drug, which could be a breakthrough in treating metastatic melanomas. This research, conducted with National Institutes for Quantum Science and Technology in conjunction with other institutions was published on 20 January 2025 in European Journal of Nuclear Medicine and Molecular Imaging. TAT
is a type of radiotherapy which uses drugs that emit alpha particles. Alpha particles have a shorter range than other radioactive emission forms (beta or gamma). Due to their larger mass, the alpha particles have a higher energy which can be beneficial in destroying cancer cells. The researchers identified the optimal hydrophilic links to improve tumor targeting, and minimize off-target accumulation. The team then designed an astatine-211(211At)-labeled a-melanocyte-stimulating hormone (a-MSH) peptide analog called [211At]NpG-GGN4c to specifically target melanocortin-1 receptors (MC1R), which are overexpressed in melanoma cells. “Since the tagged peptide was also receptor-targeted, it allowed for a high tumor selectivity while minimizing radiation exposure to the surrounding tissues,” comments Dr. Suzuki.
After testing the synthesized molecules on B16F10 mice with melanoma, the researchers conducted a biodistribution study, comparing tumor uptake and clearance of organs as well as the stability of the compounds. Dr. Uehara elaborates the method, saying “We treated the mice with different doses of the compound while monitoring the tumor response, body weight, and survival rates over time. We found a dose-dependent inhibitory effect in a melanoma-bearing mouse model, confirming the effectiveness of our approach.”
that the findings were impressive. The NpG GGN4c [211At]showed high accumulation of tumors as well as rapid clearance in non-targeted organs. This confirmed its specificity to MC1R melanoma cell. The tumors were significantly suppressed in dose-dependent fashion. Additionally, [211At]showed high stability of NpG GGN4c in plasma blood, which minimized the risk for radioactive leakage into the body.
Hailing the exciting results, Dr. Suzuki affirms that the molecular design of their synthesized drug could be useful for developing other 211At-labeled radiopharmaceuticals. He adds, ” “We believe our approach could open up new possibilities for treating refractory cancers beyond melanoma.”
the team is hopeful of promoting a TAT based on 211At for clinical use.” “If successfully translated into human trials, this therapy may emerge as a viable treatment option for patients with advanced melanoma in the coming years,” speculates Dr. Suzuki. “This could provide new therapeutic opportunities for patients with refractory cancer.”
