Radioimmunotherapy with radioactive nanoparticles: Biological doses and treatment efficiency for vascularized tumors with or without a central hypoxic area

Research Center in Physics of Matter and Radiation, Laboratoire d'Analyses par Réactions Nucléaires, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium.
Medical Physics (Impact Factor: 2.64). 04/2010; 37(4):1826-39. DOI: 10.1118/1.3368599
Source: PubMed


Radioactive atoms attached to monoclonal antibodies are used in radioimmunotherapy to treat cancer while limiting radiation to healthy tissues. One limitation of this method is that only one radioactive atom is linked to each antibody and the deposited dose is often insufficient to eradicate solid and radioresistant tumors. In a previous study, simulations with the Monte Carlo N-Particle eXtended code showed that physical doses up to 50 Gy can be delivered inside tumors by replacing the single radionuclide by a radioactive nanoparticle of 5 nm diameter containing hundreds of radioactive atoms. However, tumoral and normal tissues are not equally sensitive to radiation, and previous works did not take account the biological effects such as cellular repair processes or the presence of less radiosensitive cells such as hypoxic cells.
The idea is to adapt the linear-quadratic expression to the tumor model and to determine biological effective doses (BEDs) delivered through and around a tumor. This BED is then incorporated into a Poisson formula to determine the shell control probability (SCP) which predicts the cell cluster-killing efficiency at different distances "r" from the center of the tumor. BED and SCP models are used to analyze the advantages of injecting radioactive nanoparticles instead of a single radionuclide per vector in radioimmunotherapy.
Calculations of BED and SCP for different distances r from the center of a solid tumor, using the non-small-cell lung cancer as an example, were investigated for 90Y2O3 nanoparticles. With a total activity of about 3.5 and 20 MBq for tumor radii of 0.5 and 1.0 cm, respectively, results show that a very high BED is deposited in the well oxygenated part of the spherical carcinoma.
For either small or large solid tumors, BED and SCP calculations highlight the important benefit in replacing the single beta-emitter 90Y attached to each antibody by a 90Y2O3 nanoparticle.

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    • "Bouchat et al. modeled Y-90 labeled antibody biodistribution by Monte Carlo code and showed that RIT would not result in tumor doses sufficient to treat solid tumors such as lung cancer (biological effective dose < 60 Gy). Using a similar modeling system, they showed that radioactive nanoparticles with ~100 Y-90 atoms per nanoparticle can substantially increase the biologic effective dose deposited to a solid tumor (Bouchat et al. 2010). Additionally, radioisotopes that are usually insoluble in body fluids can be encapsulated within nanoparticles, allowing them to be sequestered until delivery at the target (Khan et al. 2008). "

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