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News article31 October 2018

Alpha-particle emitters encapsulated in nanoparticles for targeted radionuclide therapy

Figure 1: Symbolic image of alpha-particle cascade emitters located in the centre of core-shell nanoparticles. Sufficiently thick shells from heavy materials such as gold can confine the radioactive daughter nuclides created in the decay cascade. All alph
Symbolic image of alpha-particle cascade emitters located in the centre of core-shell nanoparticles
© EU, 2018

JRC scientists explored the potential of encapsulation of alpha-particle emitters in nanoparticles - also referred to as alpha-particle nanogenerators - for safer radionuclide therapy. This is used in the fight against cancer for example.

Targeted radionuclide therapy in cancer treatment is a rapidly evolving field, as it delivers locally therapeutic radiation doses even in disseminated diseases where beam radio therapies are not applicable.

So far, beta-emitters play a dominating role, however due to the limited linear energy transfer of beta-radiation a cell must be hit by many thousands of beta-particles before it is successfully killed.

The use of alpha particles emitters solves this problem, as they can deliver much higher therapeutic radiation doses to small volumes at high dose rate. However, they also may cause unspecific off-target irradiation and unintentional toxicity.

This is especially critical if alpha-particle emitters are used that are at the starting point of a decay chain as for example 225-actinium (225Ac, see Fig.1). Conventional chemical bonding to a tumour seeking molecule cannot ensure that the alpha-emitters (221-francium [221Fr], 217-astatine [217At] and 213-bismut [213Bi], see Fig.1) will emit their alpha-particles in the diseased tissue.

Whenever an alpha-particle is emitted the created daughter radionuclide will receive a recoil energy that is about 10.000 times higher than the chemical bond strength, and it will become dissociated from its targeting molecule. The safe encapsulation of all alpha emitters in the decay chain in properly sized nano-carriers may avoid this problem.

But the nano-carriers that guarantee 100% confinement of all daughter radionuclides are frequently too large to preserve good tumour penetration and uptake.

In this respect it is important to understand how much of the fraction of alpha particles will be emitted from outside the nanoparticle when its size is reduced below the radius that guarantees complete confinement of all radioactive daughter nuclides.

Therefore, JRC scientists developed a model for spherical nanoparticles that allows an estimate of the fraction of recoiling alpha particle emitters that may escape from the nanoparticles a s function of their size. It is expected that this work may improve the application safety of alpha-particle emitters such as 225-actinium and 223-radium for cancer therapy.

Read more in: U. Holzwarth et al.: A random walk approach to estimate the confinement of alpha-particle emitters in nanoparticles for targeted radionuclide therapy, EJNMMI Radiopharmacy and Chemistry (2018), doi: 10.1186/s41181-018-0042-3

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A random walk approach to estimate the confinement of alpha-particle emitters in nanoparticles for targeted radionuclide therapy

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Publication date
31 October 2018