A Comprehensive Review of Diffusing Alpha-Emitters Radiation Therapy (DaRT): From Dosimetry to Its Biological Effectiveness

Diffusing alpha-emitters radiation therapy (DaRT) represents a groundbreaking development in cancer therapy, offering a solution to the limitations of conventional radiation therapy. By deploying 224Ra embedded seeds, DaRT achieves targeted delivery of high-dose alpha particles directly to tumor sites, showing considerable efficacy in tumor control and minimal damage to adjacent healthy tissues. This comprehensive review analyzes the published literature regarding mechanisms, seed production, dose calculation, measurement, and biological experiments related to DaRT. It includes in-depth discussions on mathematical models, Monte Carlo simulations for dose distribution, real-time in vivo dosimetry developments, and biological experiments both in vitro and in vivo. Clinical trial outcomes are also examined to evaluate the therapy's effectiveness in various cancer types. DaRT utilizes 224Ra-labeled seeds, using the decay chain of 224Ra to deliver alpha particles effectively within a tumor. Several asymptotic diffusion-leakage models were developed to calculate the alpha dose distribution of DaRT. In vivo dosimetry techniques have been developed for real-time monitoring. Biological experiments demonstrated the cytotoxic effects of DaRT across various cancer cells, with varying radiosensitivity. Additionally, the enhanced effects of combined therapy with chemotherapy and immunotherapy were suggested by many in vivo studies. Clinical trials have shown high complete response rate in squamous cell carcinoma, with minimal side effects, suggesting DaRT's feasibility and safety. DaRT emerges as a highly localized cancer treatment method with minimal side effects compared to traditional radiation therapy. It directly ablates tumors and potentially enhances immune responses, indicating a significant advance in cancer therapy. Future research and ongoing clinical trials will further elucidate its efficacy across different cancer types and in combination with other treatments.