Clustering effects in nanoparticle-enhanced β⁻ emitting internal radionuclide therapy: a Monte Carlo study

Abstract

We investigate the effects of an increase in the production of secondary electrons when a β− source commonly used in internal radionuclide therapy, 67Cu, is radiolabelled to a super-paramagnetic iron oxide nanoparticle (SPION), with specific emphasis on the role of SPION cluster size and geometry. A positive relationship is found between the degree to which the nanoparticles are clustered and the associated radio-enhancement effects, with cluster population size playing a major role, as well as SPION separation within a cluster and the distance between clusters. Our simulation results indicate that SPIONs labelled with 67Cu can induce a nonlinear amplification in the number of secondary electrons produced of up to 4% in bulk, with localised regions of nearer inter-SPION separation producing an increase of over 400% for a 20 nm average SPION separation. Such variation in enhancement due to local concentration effects may help identify clinical strategies that enhance efficacy for a given radiation dosage, or achieve equal efficacy with reduced radiation dosage.

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“…oxidative stress, immune responses, as well as DNA damage and repair responses) rather than an enhancement in physical radiation dose (Butterworth et al 2012;Jain et al 2011;Schuemann et al 2020). Furthermore, nanoparticles radiolabelled with therapeutic isotopes commonly used in nuclear medicine may offer a more promising strategy for radioenhancement effects given the relatively low-energy (kV) regime of emitters commonly used in internal radionuclide therapy (Gholami et al 2019;Maschmeyer et al 2020).…”

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“…Dose-enhancement was due to the release of secondary electrons from the IONPs following interaction with the α- or β-particles emitted by the radionuclides. Maschmeyer et al ( 2020 ) conduced a MC dose-modeling study to estimate the nano-Radio Enhancement Ratio (nano-RER) defined as the ratio of the number of secondary electrons produced with/without 5 nm superparamagnetic iron oxide NPs (SPIONs) bound to 67 Cu. The nano-RER for a single [ 67 Cu]Cu-SPION decreased dramatically as the distance from the SPION increased.…”