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

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.

Determination of biological vector characteristics and nanoparticle dimensions for radioimmunotherapy with radioactive nanoparticles.

Radioimmunotherapy with biological vector labeled with radioactive nanoparticles is investigated from a dosimetric point of view. Beta (32P, 90Y) and low-energy X-ray radionuclides (103Pd) are considered. Dose distributions inside solid tumors have been calculated using MCNPX 2.5.0. Nanoparticle dimensions and biological vector characteristics are also determined in order to reach the 50 Gy prescribed dose inside the entire tumor volume. The worst case of an avascular tumor is considered. Results show that for beta-emitting nanoparticles, a set of data (covering fraction, biological half-life, and nanoparticle radius) can be found within acceptable ranges (those of classical radioimmunotherapy). These sources (with Emax approximately few MeV) can be used for the treatment of tumors with a maximum diameter of about 1 cm. Low-energy X-rays (E<25 keV) can be used to extend the range of tumor diameter to 4-5 cm but require very tight biological vector characteristics.

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.

Structure of 12Be: intruder d-wave strength at N=8.

The breaking of the N=8 shell-model magic number in the 12Be ground state has been determined to include significant occupancy of the intruder d-wave orbital. This is in marked contrast with all other N=8 isotones, both more and less exotic than 12Be. The occupancies of the [FORMULA: SEE TEXT]orbital and the [FORMULA: SEE TEXT], intruder orbital were deduced from a measurement of neutron removal from a high-energy 12Be beam leading to bound and unbound states in 11Be.

Observation of excited states in 5H.

The 5H system was produced in the 3H(t,p)5H reaction studied with a 58 MeV tritium beam at small c.m. angles. High statistics data were used to reconstruct the energy and angular correlations between the 5H decay fragments. A broad structure in the 5H missing mass spectrum showing up above 2.5 MeV was identified as a mixture of the 3/2+ and 5/2+ states. The data also present evidence that the 1/2+ ground state of 5H is located at about 2 MeV.