Economic implications of the "Green Revolution" and the strategy of agricultural development in West Pakistan

Original document thought to be incomplete

Preclinical Evaluation of Biodistribution and Toxicity of [211At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer

Watabe T., Kaneda-Nakashima K., Kadonaga Y., et al. Preclinical Evaluation of Biodistribution and Toxicity of [211At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer. International Journal of Molecular Sciences 25, 5667 (2024); https://doi.org/10.3390/ijms25115667.Astatine (211At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the 211At-labeled prostate-specific membrane antigen (PSMA) compound ([211At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [211At]PSMA-5 was administered to both normal male ICR mice (n = 85) and cynomolgus monkeys (n = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day (n = 10 per group) and 14 days (n = 5 per group). Monkeys were observed 24 h post-administration of [211At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [211At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of 211At using a cyclotron supports its applicability for clinical use