Purpose: to estimate the dose to adjacent tissue and distant organs in clinical trials with Diffusing Alpha-emitters Radiation Therapy for oral cavity and skin squamous cell carcinoma (SCC) tumors.
Methods: blood and urine samples were taken from 24 patients treated with 14-338 ÂµCi Ra-224, at days 5, 11 and 30 post treatment, and measured to determine the specific activity of Pb-212. Results were compared with biokinetic modelling, and used to estimate the organ dose. The alpha particle dose around each seed was estimated from autoradiography measurements in murine SCC. The beta and gamma dose was calculated using the EGSnrc code, with and without considering the diffusion of Ra-224 daughter atoms near the seed.
Results: the measured Pb-212 activities in blood and urine samples were consistent to leading order with the predictions of the biokinetic model. The average alpha particle dose to the kidneys and bone marrow was 2Â±1 cGy and 0.9Â±0.6 cGy respectively. Preclinical autoradiography measurements indicate that the alpha dose exceeds 10 Gy up to 2.5-3 mm from the seed, rapidly dropping to negligible levels at larger distances. The beta and gamma dose drops below 1 Gy ~3.5 mm away from the seed. The assumption that all beta and gamma emissions originate from the seed provides an excellent approximation to the case of Ra-224 daughter atom diffusion. Clinically, no radiation-related side effects were observed either locally or in distant organs.
Conclusion: Clinical data demonstrates the excellent radiation safety of Diffusing Alpha-emitters Radiation Therapy, both locally and at a distance. Biokinetic modelling provides reliable order-of-magnitude estimates for the systemic dose. The alpha dose is limited to a few mm around each seed. The beta and gamma dose is negligible already 3 mm away from the seed and can be accurately calculated using standard Monte Carlo codes.
Funding Support, Disclosures, and Conflict of Interest: L. Arazi, M. Schmidt, T. Cooks, Y. Keisari and I. Kelson are minor share holders in Alpha TAU Medical (ATM).