RESUMO
PURPOSE: The main objective of the present study was to compare the 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) and 3'-[18F]fluoro-3'-deoxythymidine ([18F]-FLT) PET imaging biomarkers for the longitudinal follow-up of small animal proton therapy studies in the context of hepatocellular carcinoma (HCC). PROCEDURES: SK-HEP-1 cells were injected into NMRI nude mice to mimic human HCC. The behavior of [18F]-FDG and [18F]-FLT tumor uptake was evaluated after proton therapy procedures. The proton single-fraction doses were 5, 10, and 20 Gy, with a dose rate of 10 Gy/min. The experimental protocol consisted of 8 groups of 10 mice, each group experiencing a particular dose/radiotracer condition. A reference PET exam was performed on each mouse the day before the irradiation procedure, followed by PET exams every 3 days up to 16 days after irradiation. RESULTS: [18F]-FDG uptake showed a linear dose-dependent increase in the first days after treatment (37%, p < 0.05), while [18F]-FLT uptake decreased in a dose-dependent manner (e.g., 21% for 5 Gy compared to 10 Gy, p = 1.1e-2). At the later time point, [18F]-FDG normalized activity showed an 85% decrease (p < 0.01) for both 10 and 20 Gy doses and no variation for 5 Gy. Conversely, a significant 61% (p = 0.002) increase was observed for [18F]-FLT normalized activity at 5 Gy and no variation for higher doses. CONCLUSION: We showed that the use of the [18F]-FDG and [18F]-FLT radiolabeled molecules can provide useful and complementary information for longitudinal follow-up of small animal proton therapy studies in the context of HCC. [18F]-FDG PET imaging enables a treatment monitoring several days/weeks postirradiation. On the other hand, [18F]-FLT could represent a good candidate to monitor the treatment few days postirradiation, in the context of hypo-fractioned and close irradiation planning. This opens new perspectives in terms of treatment efficacy verification depending on the irradiation scheme.
Assuntos
Carcinoma Hepatocelular , Didesoxinucleosídeos , Fluordesoxiglucose F18 , Neoplasias Hepáticas , Tomografia por Emissão de Pósitrons , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Didesoxinucleosídeos/química , Didesoxinucleosídeos/farmacocinética , Modelos Animais de Doenças , Feminino , Fluordesoxiglucose F18/química , Fluordesoxiglucose F18/farmacocinética , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Camundongos , Camundongos Nus , Terapia com PrótonsRESUMO
PURPOSE: With the increase in proton therapy centers, there is a growing need to make progress in preclinical proton radiation biology to give accessible data to medical physicists and practicing radiation oncologists. METHODS: A cyclotron usually producing radioisotopes with a proton beam at an energy of about 25 MeV after acceleration, was used for radiobiology studies. Depleted silicon surface barrier detectors were used for the beam energy measurement. A complementary metal oxide semiconductor (CMOS) sensor and a plastic scintillator detector were used for fluence measurement, and compared to Geant4 and an in-house analytical dose modeling developed for this purpose. Also, from the energy measurement of each attenuated beam, the dose-averaged linear energy transfer (LETd ) was calculated with Geant4. RESULTS: The measured proton beam energy was 24.85 ± 0.14 MeV with an energy straggling of 127 ± 22 keV before scattering and extraction in air. The measured flatness was within ± 2.1% over 9 mm in diameter. A wide range of LETd is achievable: constant between the entrance and the exit of the cancer cell sample ranging from 2.2 to 8 keV/µm, beyond 20 keV/µm, and an average of 2-5 keV/µm in a scattering spread-out Bragg peak calculated for an example of a 6-mm-thick xenograft tumor. CONCLUSION: The dosimetry and the characterization of a 25-MeV proton beam line for preclinical radiobiology research was performed by measurements and modeling, demonstrating the feasibility of delivering a proton beam for preclinical in vivo and in vitro studies with LETd of clinical interest.
Assuntos
Prótons , Radiobiologia/instrumentação , Radiometria/instrumentação , Método de Monte Carlo , Doses de RadiaçãoRESUMO
PURPOSE: The lack of evidence of biomarkers identifying patients who would benefit from proton therapy has driven the emergence of preclinical proton irradiation platforms using advanced small-animal models to mimic clinical therapeutic conditions. This study aimed to determine the optimal physical parameters of the proton beam with a high radiation targeting accuracy, considering small-animal tumors can reach millimetric dimensions at a maximum depth of about 2 cm. METHODS AND MATERIALS: Several treatment plans, simulated using Geant4, were generated with different proton beam features to assess the optimal physical parameters for small-volume irradiations. The quality of each treatment plan was estimated by dose-volume histograms and gamma index maps. RESULTS: Because of its low-energy straggling, low-energy proton (<50 MeV) single-field irradiation can generate homogeneous spread-out Bragg peaks to deliver a uniform dose in millimeter-sized tumors, while sparing healthy tissues located within or near the target volume. However, multifield irradiation can limit the dose delivered in critical structures surrounding the target for attenuated high-energy beams (E > 160 MeV). CONCLUSION: Low-energy proton beam platforms are suitable for precision irradiation for translational radiobiology studies.
Assuntos
Transferência Linear de Energia/fisiologia , Neoplasias/patologia , Neoplasias/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Animais , Modelos Animais de Doenças , Método de Monte Carlo , Transplante de Neoplasias , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/efeitos adversos , Lesões Experimentais por Radiação/prevenção & controle , Dosagem Radioterapêutica , Transplante Heterólogo , Carga TumoralRESUMO
PURPOSE: Due to the considerable development of proton radiotherapy, several proton platforms have emerged to irradiate small animals in order to study the biological effectiveness of proton radiation. A dedicated analytical treatment planning tool was developed in this study to accurately calculate the delivered dose given the specific constraints imposed by the small dimensions of the irradiated areas. METHODS: The treatment planning system (TPS) developed in this study is based on an analytical formulation of the Bragg peak and uses experimental range values of protons. The method was validated after comparison with experimental data from the literature and then compared to Monte Carlo simulations conducted using Geant4. Three examples of treatment planning, performed with phantoms made of water targets and bone-slab insert, were generated with the analytical formulation and Geant4. Each treatment planning was evaluated using dose-volume histograms and gamma index maps. RESULTS: We demonstrate the value of the analytical function for mouse irradiation, which requires a targeting accuracy of 0.1 mm. Using the appropriate database, the analytical modeling limits the errors caused by misestimating the stopping power. For example, 99% of a 1-mm tumor irradiated with a 24-MeV beam receives the prescribed dose. The analytical dose deviations from the prescribed dose remain within the dose tolerances stated by report 62 of the International Commission on Radiation Units and Measurements for all tested configurations. In addition, the gamma index maps show that the highly constrained targeting accuracy of 0.1 mm for mouse irradiation leads to a significant disagreement between Geant4 and the reference. This simulated treatment planning is nevertheless compatible with a targeting accuracy exceeding 0.2 mm, corresponding to rat and rabbit irradiations. CONCLUSION: Good dose accuracy for millimetric tumors is achieved with the analytical calculation used in this work. These volume sizes are typical in mouse models for radiation studies. Our results demonstrate that the choice of analytical rather than simulated treatment planning depends on the animal model under consideration.
Assuntos
Terapia com Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Animais , Simulação por Computador , Camundongos , Método de Monte Carlo , Células Neoplásicas Circulantes , Imagens de Fantasmas , Terapia com Prótons/instrumentação , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/instrumentação , ÁguaRESUMO
PURPOSE: The real-time monitoring of the spread-out Bragg peak would allow the planned dose delivered during treatment to be directly verified, but this poses a major challenge in modern ion beam therapy. A possible method to achieve this goal is to exploit the production of secondary particles by the nuclear reactions of the beam with the patient and correlate their emission profile to the planned target volume position. In this study, we present both the production rate and energy spectra of the prompt-γ produced by the interactions of the 12 C ion beam with a polymethyl methacrylate (PMMA) target. We also assess three different Monte Carlo models for prompt-γ simulation based on our experimental data. METHODS: The experiment was carried out at the GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany with a 220 MeV/u 12 C ions beam impinging on a 5× 5× 20 cm3 polymethyl methacrylate beam stopping target, with the prompt-γ being detected by a hexagonally-shaped barium fluoride scintillator with a circumscribed radius of 5.4 cm and a length of 14 cm, placed at 60° and 90° with respect to the beam direction. Monte Carlo simulations were carried out with three different hadronic models from the Geant4 code: binary ion cascade (BIC), quantum molecular dynamics (QMD), and Liege intranuclear cascade (INCL++ ). RESULTS: An experimental prompt-γ yield of 1.06 × 10-2 sr-1 was measured at 90°. A good agreement was observed between the shapes of the experimental and simulated energy spectra, especially with the INCL++ physics list. The prompt-γ yield obtained with this physics list was compatible with the measurement within 2σ, with a relative difference of 26% on average. BIC and QMD physics lists proved to be less accurate than INCL++ , with the difference between the measured and simulated yields exceeding 100%. The differences between the three physics lists were ascribed to important discrepancies between the models of the physical processes producing prompt-γ emissions. CONCLUSION: In conclusion, this study provides prompt-γ yield values in agreement with previously published results for different carbon ions energies. This work demonstrates that the INCL++ physics list from Geant4 is more accurate than BIC and QMD to reproduce prompt-γ emission properties.
Assuntos
Benchmarking , Radioterapia com Íons Pesados , Carbono , Humanos , Método de Monte Carlo , Fenômenos Físicos , RadiometriaRESUMO
We measured the physical and radiobiological characteristics of 1 GeV protons for possible applications in stereotactic radiosurgery (image-guided plateau-proton radiosurgery). A proton beam was accelerated at 1 GeV at the Brookhaven National Laboratory (Upton, NY) and a target in polymethyl methacrylate (PMMA) was used. Clonogenic survival was measured after exposures to 1-10 Gy in three mammalian cell lines. Measurements and simulations demonstrate that the lateral scattering of the beam is very small. The lateral dose profile was measured with or without the 20-cm plastic target, showing no significant differences up to 2 cm from the axis A large number of secondary swift protons are produced in the target and this leads to an increase of approximately 40% in the measured dose on the beam axis at 20 cm depth. The relative biological effectiveness at 10% survival level ranged between 1.0 and 1.2 on the beam axis, and was slightly higher off-axis. The very low lateral scattering of relativistic protons and the possibility of using online proton radiography during the treatment make them attractive for image-guided plateau (non-Bragg peak) stereotactic radiosurgery.