Heterogeneity of dose distribution in normal tissues in case of radiopharmaceutical therapy with alpha-emitting radionuclides

Heterogeneity of dose distribution has been shown at different spatial scales in diagnostic nuclear medicine. In cancer treatment using new radiopharmaceuticals with alpha-particle emitters, it has shown an extensive degree of dose heterogeneity affecting both tumour control and toxicity of organs at risk. This review aims to provide an overview of generalized internal dosimetry in nuclear medicine and highlight the need of consideration of the dose heterogeneity within organs at risk. The current methods used for patient dosimetry in radiopharmaceutical therapy are summarized. Bio-distribution and dose heterogeneities of alpha-particle emitting pharmaceutical Ra-223 (Xofigo) within bone tissues are presented as an example. In line with the strategical research agendas of the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radiation Dosimetry Group (EURADOS), future research direction of pharmacokinetic modelling and dosimetry in patient radiopharmaceutical therapy are recommended.