Modelling and dosimetry for alpha-particle therapy

Abstract

As a consequence of the high potency and short range of alpha-particles, radiopharmaceutical therapy with alpha- particle emitting radionuclides is a promising treatment approach that is under active pre-clinical and clinical investigation. To understand and predict the biological effects of alpha-particle radiopharmaceuticals, dosimetry is required at the micro or multi-cellular scale level. At such a scale, highly non-uniform irradiation of the target volume may be expected and the utility of a single absorbed dose value to predict biological effects comes into question. It is not currently possible to measure the pharmacokinetic input required for micro scale dosimetry in humans. Accordingly, pre-clinical studies are required to provide the pharmacokinetic data for dosimetry calculations. The translation of animal data to the human requires a pharmacokinetic model that links macro- and micro-scale pharmacokinetics thereby enabling the extrapolation of micro-scale kinetics from macroscopic measurements. These considerations along with a discussion of the appropriate physical quantity and related units for alpha-particle radiopharmaceutical therapy are examined in this review.

Fig. (1)

Schematic of three potential alpha-emitter distributions (red dots). In (a), the distribution of emitters is uniformly distributed in the trabecular marrow cavity. In panel (b), the agent localizes to the bone surface and only irradiates a portion of the marrow. In (c), the emitters are distributed around tumor cells in the marrow. Each of these configurations will have a different impact on marrow toxicity. Case (a) can be accommodated by single value, absorbed fraction-based calculations. The other two scenarios are best handled by Monte Carlo methods that yield dose-volume histograms to calculate radiobiological parameters that can relate the dose-volume histogram to biological efficacy or toxicity.

Fig. (2)

Schematic representation of the kidney (a) depiction of realistic anatomy (from http://www.uic.edu/classes/bios/bios100/-lecturesf04am/kidney01a.jpg) and (b) idealized model of a nephron that may be used in Monte Carlo calculations once the distribution of emissions is localized to the different micro-scale kidney compartments.