Dosimetry and Radiobiology of Alpha-Particle Emitting Radionuclides

Background: Radiopharmaceutical therapy is a cancer treatment modality by which radiation is delivered directly to targeted tumor cells or to their microenvironment. This makes it possible to deliver highly potent alpha-particle radiation. The short-range and highly potent nature of alpha-particles require a dosimetry methodology that considers microscale distributions of the alpha-emitting agent. The high energy deposition density along an alpha-particle track causes a spectrum of DNA lesions. The majority of these are irreparable DNA double-stranded breaks. Accordingly the biologic effects of alpha- particles are largely impervious to the adaptive and resistance mechanism that renders other therapeutics ineffectual. Objectives: In this review, the radiobiology and dosimetry of alpha-particle emitting radionuclides as related to their use in radiopharmaceutical therapy, are presented. Conclusion: Alpha-particle emitter radiopharmaceutical therapy is distinguished from other treatment modalities. Its safe clinical use requires an understanding of its unique dosimetry and radiobiology.