Continuous administration of alpha radionuclide therapy: a proof-of-concept based on black hole like-dynamics.

. Targeted radionuclide therapy using alpha-particle-emitting radiopharmaceuticals (alpha-RPT) is increasingly recognized as an effective, safe and economically viable clinical treatment. However, it is restricted to few cancer types, and to metastatic or unresectable tumors as a palliative treatment. Broader implementation of alpha-RPT across cancer types and earlier disease stages is hampered by limitations of current clinical dosimetry. Alpha-RPT administration regimens rely on fixed protocols for intermittent radioactivity (RT) administration, without dynamic adjustments. This study provides a computational proof-of-concept of continuous dynamic-discretized RT administration strategy for alpha-RPT inspired by black hole (BH)-like dynamics.BHs can exhibit impressive forms of convergence, stability and robustness, ensuring a trapped region, in which matter cannot escape from it. When extrapolated to cancer therapy, the tumor is analogically considered as a mass inside a BH, in which the BH center represents the cancer remission, and the alpha-RPT administration acts as the gravitational attraction pulling the tumor mass towards the center (where a complete remission is reached). Using a recently validated mathematical model of Actinium-225 alpha-RPT in a Murine breast cancer model, we were able to predict geometro-radiopharmacokinetics and tumor dynamics for different number of tumor cells, discretization intervals, and a wide variation range of tumor parameters.Our results show that BH-like RT administration can significantly reduce total administered RT and treatment duration compared with current clinical practice based on intermittent administration, while maintaining therapeutic efficacy, even under highly uncertain tumor dynamics. Reductions in treatment duration up to 48.8% were obtained, as well as reductions in maximum/average RT administration up to 54.3%/81.1%.. These findings suggest that adaptive control strategies may overcome key limitations of current alpha-RPT protocols, allowing dynamically adjusted RT administration according to tumor state data obtained from biomarker data and/or theranostic imaging. This strategy holds the potential to refine clinical protocols and expand alpha-RPT beyond its current limitations, establishing the 'biological BH' as a new high-impact foundation for spreading alpha emitting RPT to primary cancers and multiple cancer types.