Vincent Nuttens

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 5nm 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 Y290O3. 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 34MBq for tumor radii of 0.5 and 1.0cm, respectively, viable tumor cells can receive doses of up to 50Gy, 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.

Comparison of the clonogenic survival of A549 non-small cell lung adenocarcinoma cells after irradiation with low-dose-rate beta particles and high-dose-rate X-rays.

Abstract Purpose: Lung cancer is the leading cause of cancer-related death. Among the new modalities to treat cancer, internal radiotherapy seems to be very promising. However, the achievable dose-rate is two orders of magnitude lower than the one used in conventional external radiotherapy, and data has to be collected to evaluate the cell response to highlight the potential effectiveness of low-dose-rate beta particles irradiation. This work investigates the phosphorus beta irradiation (32P) dose response on the clonogenicity of human A549 non-small cell lung adenocarcinoma cells and compares it to high-dose-rate X-irradiations results. Materials and methods: Cell survival was evaluated by a colony forming assay eight days after low-dose-rate 32P beta irradiations (0.8 Gy/h) and high-dose-rate X-ray irradiations (0.855 Gy/min). Results: Survival curves were obtained for both types of irradiations, and showed hyper-radiosensitivity at very low doses. Radiosensitivity parameters were obtained by using the linear-quadratic and induced-repair models. Conclusions: Comparison with high-dose-rate X-rays shows a similar surviving fraction, confirming the effectiveness of beta particles for tumor sterilization.

Determination of the prescription dose for biradionuclide permanent prostate brachytherapy

A model based on the linear quadratic model that has been corrected for repopulation, sublethal cell damage repair, and RBE effect has been used to determine the prescription dose for prostate permanent brachytherapy using seeds loaded with a mixture of 103Pd and 125I or a mixture of 103Pd and 131Cs. The prescription dose was determined by comparing the tumor cell survival fractions between the considered biradionuclide seed implant and one monoradionuclide seed implant chosen from 103Pd, 125I, and 131Cs. Prostate edema is included in the model. The influence of the value of the radiobiological parameters and RBE were also investigated. Two mixtures of radionuclides were considered: 103Pd0.75-125I0.25 and 103Pd0.25-131Cs0.75, where the subscripts indicate the fractions of total initial internal activity in the biradionuclide seed. These fractions were selected in order to obtain a dose distribution that lies between that of 103Pd and 125I/131Cs. As expected, the computed prescription dose values are dependent on the model parameters (edema half-life and magnitude, radiobiogical parameters, and RBE). The radionuclide used as a benchmark also has a strong impact on the derived prescribed dose. The large uncertainties in the radiobiological parameters and RBE values produce big errors in the computed prescribed dose. Averaged over the range of all the parameters and depending on the radionuclide used as a benchmark (in subscript), the derived prescription dose for the first mixture (PdI) would be: D(PdI)(Pd)=142(+15)(-16) Gy and D(PdI)(I)=142(+6)(-8) Gy; and D(PdCs)(Pd)=128(+13)(-13) Gy and D(PdCs)(Cs)=115(+6)(-7) Gy for the PdCs mixture. The uncertainties could be reduced if the radiobiological parameters and RBE value were known more accurately. However, as edema characteristics are patient dependent and can be obtained only after the treatment, an unpredictable error is unavoidable.

AAPM TG-43U1 formalism adaptation and monte carlo dosimetry simulations of multiple-radionuclide brachytherapy sources.

This paper presents a preliminary study on multiple-radionuclide sources for brachytherapy. An adaptation of the AAPM TG-43U1 formalism is proposed in order to derive the dosimetry parameters of multiple-radionuclide sources from mono-radionuclides. The adapted formalism is applied to a bi-radionuclide case with the help of Monte Carlo calculations (MCNPX 2.5.0). InterSource seed loaded with 103Pd and 125I was chosen. This combination promotes a higher dose rate than InterSource125 (loaded with 125I) and deeper tissue penetration than InterSource103 (loaded with 103Pd) while reducing the dose at long distance (beyond 2.5 cm) relative to InterSource125. In conclusion, this work shows the benefits of combining different radionuclides inside the same seed and proposes an adaptation of the AAPM TG-43U1 formalism for the implementation of multiple-radionuclide sources in current treatment planning systems.

Cold head maintenance with minimal service interruption

Turn-key superconducting magnet systems are increasingly conduction-cooled by cryogenerators. Gifford-McMahon systems are reliable and cost effective, but require annual maintenance. A usual method of servicing is replacing the cold head of the cryocooler. It requires a complicated design with a vacuum chamber separate from the main vacuum of the cryostat, as well as detachable thermal contacts, which add to the thermal resistance of the cooling heat path and reduce the reliability of the system. We present a rapid warm-up scheme to bring the cold head body, which remains rigidly affixed to the cold mass, to room temperature, while the cold mass remains at cryogenic temperature. Electric heaters thermally attached to the cold head stations are used to warm them up, which permits conventional cold head maintenance with no danger of contaminating the inside of the cold head body. This scheme increases the efficiency of the cooling system, facilitates annual maintenance of the cold head and returning the magnet to operation in a short time.

Magnet Design of the New IBA Cyclotron for PET Radio-isotope Production

An innovative isochronous cyclotron for PET isotope production has been designed, constructed, tested and industrialized at Ion Beam Applications (IBA) [1]. The design has been optimized for cost-effectiveness, compactness, ease of maintenance and high performance,which are key elements considering its application in the dedicated market. This cyclotron (patent application pending) produces 18MeV protons and the cyclotron is called the Cyclone® KIUBE. Compared to the previous 18MeV proton and 9MeV deuteron machine from IBA, the Cyclone®18/9, the gap between the poles has been reduced from 30mm to 24mm and the method of pole shimming to obtain an isochronous magnetic field has been reviewed thoroughly. In early 2016, the first prototype Cyclone® KIUBEwas successfully commissioned at the IBA factory and the measured proton beam intensity outperformed the Cyclone® 18/9.

Development of the Cyclone® Kiube: A Compact, High Performance and Self-Shielded Cyclotron for Radioisotope Production

About 15 months ago, at IBA, we have launched the design, construction, tests and industrialization of an innovative isochronous cyclotron for PET isotope production (patent applications pending). The design has been optimized for cost effectiveness, compactness, ease of maintenance, activation reduction and high performances, with a particular emphasis on its application on market. Multiple target stations can be placed around the vacuum chamber. An innovative extraction method (patent applications pending) has been designed which allows to obtain the same extracted beam sizes and properties on the target window independent of the target position. INTRODUCTION This isochronous cyclotron for PET radioisotope production produces fixed energy 18MeV proton beam and is called the Cyclone® KIUBE, Figure 1. Today, three versions are available producing 100μA, 150μA and 180μA on target and the option with selfshielding is also available. Figure 1: CYCLONE® KIUBE.

Development of Cyclotrons for Proton and Particle Therapy

All particle therapy systems are modular systems built with smaller subsystems. The various modules are (1) the beam production system, (2) the beam transport system, and (3) the beam delivery system as shown in Fig. 2.1.

An NTCP Analysis of Urethral Complications from Low Doserate Mono- and Bi-Radionuclide Brachytherapy

Urethral NTCP has been determined for three prostates implanted with seeds based on 125I (145 Gy), 103Pd (125 Gy), 131Cs (115 Gy), 103Pd-125I (145 Gy), or 103Pd-131Cs (115 Gy or 130 Gy). First, DU20, meaning that 20% of the urhral volume receive a dose of at least DU20, is converted into an I-125 LDR equivalent DU20 in order to use the urethral NTCP model. Second, the propagation of uncertainties through the steps in the NTCP calculation was assessed in order to identify the parameters responsible for large data uncertainties. Two sets of radiobiological parameters were studied. The NTCP results all fall in the 19%–23% range and are associated with large uncertainties, making the comparison difficult. Depending on the dataset chosen, the ranking of NTCP values among the six seed implants studied changes. Moreover, the large uncertainties on the fitting parameters of the urethral NTCP model result in large uncertainty on the NTCP value. In conclusion, the use of NTCP model for permanent brachytherapy is feasible but it is essential that the uncertainties on the parameters in the model be reduced.