1. Med Phys. 2010 Apr;37(4):1826-39.

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

Bouchat V, Nuttens VE, Michiels C, Masereel B, Feron O, Gallez B, Vander Borght
T, Lucas S.

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. virginie.bouchat@fundp.ac.be

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

PMID: 20443505 [PubMed - indexed for MEDLINE]