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
Y
90
2
O
3
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
β
-emitter
Y
90
attached to each antibody by a
Y
90
2
O
3
nanoparticle.
An approach using physical vapor deposition technology to produce nanoparticles (NPs) containing radioactive atoms and the methodology to transfer them in pure water is investigated. NPs are ...synthesized by magnetron sputtering at high pressure and radioactive atoms are loaded on magnetron cathodes prior to sputtering. The technique was tested for gold cathode loaded with
57/58
Co and
195/196
Au. Linked to biological vector molecules, the nanoparticles can be used to enhance diagnostic sensitivity in medical imaging or to treat cancer.
Sizes and morphologies of the NPs were analyzed by electron microscopy, UV-Visible spectroscopy and atomic absorption spectroscopy. Results show well dispersed NPs with sizes varying between 5 and 10
nm. Activities of these NPs were measured with a CAPINTEC well counter and a High Purity Germanium detector system. Centrifugation analyses also demonstrate that the choice of the activated metal which can be alloyed with NPs plays an important role in the synthesis. This was confirmed by the Au–Co phase diagram that shows that cobalt cannot be included efficiently in the gold NPs conversely to gold.
► Production of cold and radioactive nanoparticles by magnetron sputtering. ► Phase diagram validation for Au/Co alloy in nanoparticle form. ► Nanoparticle functionalization by PPAA plasma. ► Water dispersion stability over time.
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
Y
2
90
O
3
. 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.
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
E
max∼few MeV) can be used for the treatment of tumors with a maximum diameter of about 1
cm. Low-energy X-rays (
Ē<25
keV) can be used to extend the range of tumor diameter to 4–5
cm but require very tight biological vector characteristics.
The competition between fusion-fission and quasi-fission in the reactions
48Ca+
208Pb
and
48Ca+
244Pu(E
* = 40MeV) is investigated using the pre-scission neutron multiciplicity distributions (
PSNMD) ...obtained with a new analysis protocol.
The space and time configurations of the dissociation of 8He into 6He+n+n, on C and Pb targets, have been explored simultaneously for the first time. The final-state interactions in the n-n and 6He-n ...channels are successfully described within a model that considers independent emission of neutrons from a Gaussian volume with a given lifetime. The dissociation on C target exhibits a dominant sequential decay through the ground state of 7He, consistent with neutrons being emitted from a Gaussian volume of r nn rms = 7.3 0.6 fm with a n-n delay in the sequential channel of 1400 400 fm/c, in agreement with the lifetime of 7He. The lower-statistics data on Pb target correspond mainly to direct breakup, and are well described using the n-n volume measured, without any n-n delay. The validity of the phenomenological model used is discussed.
It is more and more necessary to improve the sensitivity of gamma-ray spectroscopy systems, especially in nuclear astrophysics. In the case of radiative proton capture reactions, one means is to ...avoid the reactions on the target impurities by using reverse kinematics. This technique is possible with the LARN accelerator and can provide very clean cross-section measurements. For that purpose, a hydrogen standard has been carried out by means of ion implantation in silicon. In addition, a low-level setup has been put in place on a new beam line of the accelerator. A high efficiency and high resolution germanium detector is used conjointly with a double shielding. A passive lead castle shielding system is used to reduce the natural radioactivity and an active shielding consisting of an anti-cosmic veto is provided by an anticoincidence between the plastic scintillator and the gamma-ray detector. The setup allows a reduction of 70% of the background interference and provides an approximately 200 fold sensitivity gain of between 600 and 3000
keV. Some other developments have also been carried out to optimize the setup. The entire setup and the reverse kinematics have been validated by measuring the cross-section of the
13C(p,γ)
14N and
15N(p,γ)
16O reactions that present some astrophysical interest.
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
Y
90
2
O
3
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
β
-emitter
Y
90
attached to each antibody by a
Y
90
2
O
3
nanoparticle.
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