Metastatic melanoma is the most aggressive form of skin cancer. In an effort to achieve targeted therapy for metastatic melanoma, researchers recently developed a new radioactive drug that emits alpha particles.
Metastatic melanoma is the most aggressive form of skin cancer . In an effort to achieve targeted therapy for metastatic melanoma, researchers recently developed a new radioactive drug that emits alpha particles.
With their short range of emission and high energy, alpha particles are particularly promising for targeted therapies that require high energy release in the cancer tissue while minimizing the damage to nearby healthy tissues. Metastatic melanoma, also known as stage IV melanoma, is a type of skin cancer that spreads to other parts of the body. It is one of the most aggressive forms of skin cancer, with current therapies -- including immunotherapy and targeted drugs -- showing limited effectiveness. Radiotherapy is an emerging treatment for melanoma, but conventional beta-emitting radionuclide therapies have limitations due to their low energy transfer and long-range radiation, which can cause unintended damage to healthy tissues. To enhance the efficacy of radiotherapy, a research team from Japan, led by Assistant Professor Hiroyuki Suzuki from Chiba University, including Dr. Tomoya Uehara from Chiba University, Dr. Noriko S. Ishioka from National Institutes for Quantum Science and Technology, Dr. Hiroshi Tanaka from Juntendo University, Dr. Tadashi Watabe from Osaka University, adopted targeted alpha therapy as a promising alternative to conventional beta therapy. They developed an astatine-211 -labeled peptide drug that could offer a potential breakthrough for treating metastatic melanoma. The research was conducted in collaboration with the National Institutes for Quantum Science and Technology and was published in theTAT is a form of radiotherapy that involves drugs labeled with alpha particle-emitting radioisotopes. Compared to other forms of radioactive emissions , alpha particles are heavier and therefore have a short range. Owing to their greater mass, alpha particles also carry relatively higher energy, which is beneficial for the disruption of cancer cells. To develop the treatment, the researchers first identified an optimal hydrophilic linker to enhance tumor targeting and reduce off-target accumulation. The team then designed an astatine-211, 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. The synthesized peptides were then tested on B16F10 melanoma-bearing mice models, following which they conducted a biodistribution analysis where the team compared tumor uptake, clearance from organs, and the overall stability of the compound. Dr. Uehara elaborates on the methodology, 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."At]NpG-GGN4c showed high accumulation in tumors and rapid clearance from non-target organs, confirming its specificity for MC1R on melanoma cells. Monitoring tumor growth revealed significant tumor suppression in a dose-dependent manner. Furthermore, NpG-GGN4c also demonstrated high stability in blood plasma, minimizing the risk of radioactive leakage in the body. Hailing the exciting results, Dr. Suzuki affirms that the molecular design of their synthesized drug could be useful for developing otherAt-labeled radiopharmaceuticals. He says,"We believe our approach could open up new possibilities for treating refractory cancers beyond melanoma."At-based TAT."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."Hiroyuki Suzuki, Saki Yamashita, Shoko Tanaka, Kento Kannaka, Ichiro Sasaki, Yasuhiro Ohshima, Shigeki Watanabe, Kazuhiro Ooe, Tadashi Watabe, Noriko S. Ishioka, Hiroshi Tanaka, Tomoya Uehara.Researchers have developed a new type of tumor-targeted alpha-particle therapy that has the potential to generically treat several kinds of cancer, with fewer negative side effects than currently ... Researchers found that particles which are secreted by tumor cells, extracellular vesicles , displayed a high level of protein integrins alpha-v and beta-1, in patients with locally advanced and ... The U.S. Food and Drug Administration has approved a novel therapy for patients with metastatic or inoperable melanoma, an aggressive type of skin ... A new study with zebrafish shows that a deadly form of skin cancer -- melanoma -- alters the metabolism of healthy tissues elsewhere in the body. The research suggests that these other tissues could ...
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