Radioimmunotherapy with radioactive nanoparticles: first results of dosimetry for vascularized and necrosed solid tumors.
Radioimmunotherapy uses monoclonal antibodies that are still labeled with only one radioactive atom. The aim of this paper is to assess, by means of MCNPX simulations, the doses delivered around and throughout a solid tumor when the radioactive atom linked to each antibody is replaced by a 5 nm diameter nanoparticle composed of numerous radionuclides. A new model for a spherical vascularized tumor has been developed in which the antibody distributions inside the tumor can be uniform or heterogeneous. It is also possible to simulate a central necrotic core inside the tumor where the concentration of radiolabeled antibodies is assumed to be zero. Dosimetry calculations have been performed for the beta-emitting radionuclide (90)Y2O3. Preliminary results show that the irregularity of vasculature and the presence of a necrotic core have a noticeable influence on the deposited dose profiles. Moreover, with a total activity of 5 and 34 MBq for tumor radii of 0.5 and 1.0 cm, respectively, viable tumor cells can receive doses of up to 50 Gy, even if high nonuniformity of the total activity is observed in the tumor. These simulations still require accurate information about antibody characteristics and necrosis sizes but clearly confirm that the use of monoclonal antibodies conjugated to nanoparticles could lead to a considerable enhancement of treatment efficacy against cancer.
Bouchat
V
V
Laboratoire d'Analyses par Réactions Nucléaires, University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur, Belgium. bouchat@fundp.ac.be
Nuttens
V E
VE
Lucas
S
S
Michiels
C
C
Masereel
B
B
Féron
O
O
Gallez
B
B
Vander Borght
T
T
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D003198:Computer Simulation; D006801:Humans; D009010:Monte Carlo Method; D053758:Nanoparticles / Q000737:chemistry*; D009336:Necrosis / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic; D016499:Radioimmunotherapy / Q000295:instrumentation* / Q000379:methods*; D011874:Radiometry / Q000379:methods*; D012984:Software
D000906:Antibodies; D000911:Antibodies, Monoclonal