INVESTIGATION OF TUMOR CELL TOXICITY FROM PARTICLE INDUCED X-RAY EMISSION FROM A 45-MeV PROTON BEAM IRRADIATED FERRITE NANOPARTICLE

2009 ◽  
Vol 19 (03n04) ◽  
pp. 143-155 ◽  
Author(s):  
KI-HONG KIM ◽  
HONG-TAE KIM ◽  
JONG-HEE KIM ◽  
SEUNG-JUN SEO ◽  
DUCK-SOO CHUNG ◽  
...  
Keyword(s):  
Proton Beam ◽  
Proton Beam Therapy ◽  
Ferrite Nanoparticles ◽  
Cancer Center ◽  
Control Group ◽  
X Ray ◽  
Nanoparticle Distribution ◽  
Acridine Orange Staining ◽  
Horizontal Beam ◽  
Center Hospital

In order to investigate the potential cytotoxic effects of particle-induced x-ray emission (PIXE) on tumor cells, 45 MeV proton beam was irradiated on C6 glioma cell lines that had taken up alginate-coated ferrite nanoparticles (Alg-SNP). Cells were anchored in vertical 96-well dishes facing a horizontal beam where the Bragg peak was placed on the upper part of the 96-well dish. Experimental groups included cells without SNP as a control (No-SNP), and cells incubated with SNP for 6 hours (6hr-SNP) or overnight (ON-SNP). A 0 to 200 Gy proton beam from an MC50 cyclotron (Scanditronix, Sweden) at the Korea Cancer Center Hospital (Seoul, Korea) was used to irradiate each experimental group. Perinuclear Alg-SNP nanoparticle distribution was observed in glioma cells. The test groups (6hr-SNP or ON-SNP) showed an estimated 20-28% (ANOVA, P < 0.05) less cell survival compared to the control group based on MTT assay. Nuclear damage, indicating apoptosis, was present at a higher frequency in the 6hr-SNP and ON-SNP groups up to relatively low radiation dose of 100 Gy by fluorescence microscopy upon Hoechst 33342 and Acridine Orange staining. Ferrite nanoparticles alone were not cytotoxic at the experimental concentration of 0.15 mg/ml. Therefore ferrite nanoparticles may induce additional cytotoxicity from X-ray emission from potential PIXE effects. PIXE and metal nanoparticles may be developed as a therapeutic factor and prodrug for localized proton beam therapy without side effects of solid or disseminate tumors on the surrounding normal tissue.

scholarly journals A novel range telescope concept for proton CT

2022 ◽  
Author(s):  
Marc Granado-González ◽  
César Jesús-Valls ◽  
Thorsten Lux ◽  
Tony Price ◽  
Federico Sánchez
Keyword(s):  
Computed Tomography ◽  
Proton Beam ◽  
Energy Resolution ◽  
Plastic Scintillator ◽  
Proton Beam Therapy ◽  
Stopping Power ◽  
High Quality ◽  
X Ray ◽  
Proton Computed Tomography ◽  
Clinical Conditions

Abstract Proton beam therapy can potentially offer improved treatment for cancers of the head and neck and in paediatric patients. There has been asharp uptake of proton beam therapy in recent years as improved delivery techniques and patient benefits are observed. However, treatments are currently planned using conventional x-ray CT images due to the absence of devices able to perform high quality proton computed tomography(pCT) under realistic clinical conditions. A new plastic-scintillator-based range telescope concept, named ASTRA, is proposed here to measure the proton’s energy loss in a pCT system. Simulations conducted using GEANT4 yield an expected energy resolution of 0.7%. If calorimetric information is used the energy resolution could be further improved to about 0.5%. In addition, the ability of ASTRA to track multiple protons simultaneously is presented. Due to its fast components, ASTRA is expected to reach unprecedented data collection rates, similar to 10^8 protons/s.The performance of ASTRA has also been tested by simulating the imaging of phantoms. The results show excellent image contrast and relative stopping power reconstruction.

Computational evaluation of dose distribution for BNCT treatment combined with X-ray therapy or proton beam therapy

2020 ◽  
Vol 165 ◽  
pp. 109295
Author(s):  
Kenta Takada ◽  
Hiroaki Kumada ◽  
Akira Matsumura ◽  
Hideyuki Sakurai ◽  
Takeji Sakae
Keyword(s):  
Proton Beam ◽  
Dose Distribution ◽  
Proton Beam Therapy ◽  
X Ray ◽  
Computational Evaluation

scholarly journals Comparison of Proton and Photon Beam Irradiation in Radiation-Induced Intestinal Injury Using a Mouse Model

2019 ◽  
Vol 20 (8) ◽  
pp. 1894 ◽  
Author(s):  
Changhoon Choi ◽  
Chansu Lee ◽  
Sung-Won Shin ◽  
Shin-Yeong Kim ◽  
Sung Noh Hong ◽  
...  
Keyword(s):  
Proton Beam ◽  
Mouse Models ◽  
Proton Irradiation ◽  
Apoptotic Cell ◽  
Proton Beam Therapy ◽  
Tunel Assay ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Limiting Factor ◽  
X Rays ◽  
X Ray

When radiotherapy is applied to the abdomen or pelvis, normal tissue toxicity in the gastrointestinal (GI) tract is considered a major dose-limiting factor. Proton beam therapy has a specific advantage in terms of reduced doses to normal tissues. This study investigated the fundamental differences between proton- and X-ray-induced intestinal injuries in mouse models. C57BL/6J mice were irradiated with 6-MV X-rays or 230-MeV protons and were sacrificed after 84 h. The number of surviving crypts per circumference of the jejunum was identified using Hematoxylin and Eosin staining. Diverse intestinal stem cell (ISC) populations and apoptotic cells were analyzed using immunohistochemistry (IHC) and a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay, respectively. The crypt microcolony assay revealed a radiation-dose-dependent decrease in the number of regenerative crypts in the mouse jejunum; proton irradiation was more effective than X-ray irradiation with a relative biological effectiveness of 1.14. The jejunum is the most sensitive to radiations, followed by the ileum and the colon. Both types of radiation therapy decreased the number of radiosensitive, active cycling ISC populations. However, a higher number of radioresistant, reserve ISC populations and Paneth cells were eradicated by proton irradiation than X-ray irradiation, as shown in the IHC analyses. The TUNEL assay revealed that proton irradiation was more effective in enhancing apoptotic cell death than X-ray irradiation. This study conducted a detailed analysis on the effects of proton irradiation versus X-ray irradiation on intestinal crypt regeneration in mouse models. Our findings revealed that proton irradiation has a direct effect on ISC populations, which may result in an increase in the risk of GI toxicity during proton beam therapy.

Early Experience of the World’s First Single-Room Gantry Mounted Active Scanning Proton Therapy System at an Integrated Cancer Center

2020 ◽  
Author(s):  
Matthew Forsthoefel ◽  
Elizabeth Ballew ◽  
Keith R. Unger ◽  
Peter H. Ahn ◽  
Sonali Rudra ◽  
...  
Keyword(s):  
Proton Beam ◽  
Proton Therapy ◽  
Insurance Coverage ◽  
Early Experience ◽  
Cancer Center ◽  
X Ray ◽  
Proton Beam Radiotherapy ◽  
Single Room ◽  
Active Scanning ◽  
Insurance Approval

Abstract Introduction Review the early experience with a single-room gantry mounted active scanning proton therapy system implemented in the modern era. Materials and Methods All patients treated with proton beam radiotherapy (PBT) were enrolled in an institutional review board-approved patient registry. Proton beam radiotherapy was delivered with a 250 MeV gantry mounted synchrocyclotron in a single-room integrated facility within the pre-existing cancer center. Demographic data, cancer diagnoses, treatment technique, and geographic patterns were obtained for all patients. Treatment plans were evaluated for mixed modality therapy. Insurance approval data was collected for all patients treated with PBT. Results A total of 132 patients were treated with PBT between March 2018 and June 2019. The most common oncologic subsites treated included the central nervous system (22%), gastrointestinal tract (20%), and genitourinary tract (20%). The most common histologies treated included prostate adenocarcinoma (19%), non-small cell lung cancer (10%), primary CNS gliomas (8%), and esophageal cancer (8%). Rationale for PBT treatment included limitation of dose to adjacent critical organs at risk (67%), reirradiation (19%), and patient comorbidities (11%). Patients received at least one x-ray fraction delivered as prescribed (36%) or less commonly due to unplanned machine downtime (34%). Concurrent systemic therapy was administered to 57 patients (43%). Twenty-six patients (20%) were initially denied insurance coverage and required peer-to-peers (65%), written appeals (12%), secondary insurance approval (12%), and comparison x-ray to proton plans (8%) for subsequent approval. Proton beam radiotherapy approval required a median of 17 days from insurance submission. Conclusion Incorporation of PBT into our existing cancer center allowed for multidisciplinary oncologic treatment of a diverse population of patients. Insurance coverage for PBT presents as a significant hurdle and improvements are needed to provide more timely access to necessary oncologic care.

EP-1043 REIRRADIATION FOR RECURRENT MALIGNANT BRAIN TUMOR WITH X-RAY RADIOTHERAPY OR PROTON BEAM THERAPY

2012 ◽  
Vol 103 ◽  
pp. S408
Author(s):  
T. Koji ◽  
M. Mizumoto ◽  
T. Okumura ◽  
H. Ishikawa ◽  
T. Yamamoto ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Proton Beam ◽  
Proton Beam Therapy ◽  
Malignant Brain Tumor ◽  
X Ray

Deformable motion reconstruction for scanned proton beam therapy using on-line x-ray imaging

2013 ◽  
Vol 58 (24) ◽  
pp. 8621-8645 ◽  
Author(s):  
Ye Zhang ◽  
A Knopf ◽  
C Tanner ◽  
D Boye ◽  
A J Lomax
Keyword(s):  
Proton Beam ◽  
Proton Beam Therapy ◽  
Motion Reconstruction ◽  
X Ray ◽  
X Ray Imaging ◽  
On Line ◽  
Deformable Motion

scholarly journals Clinical results of proton beam therapy for twenty older patients with esophageal cancer

2015 ◽  
Vol 49 (4) ◽  
pp. 371-378 ◽  
Author(s):  
Takashi Ono ◽  
Tatsuya Nakamura ◽  
Yusuke Azami ◽  
Hisashi Yamaguchi ◽  
Yuichiro Hayashi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Proton Beam ◽  
Older Patients ◽  
Dose Range ◽  
Proton Beam Therapy ◽  
Clinical Results ◽  
Local Control Rate ◽  
High Dose ◽  
X Ray ◽  
Node Metastases

Abstract Background. In an aging society, increasing number of older patients are diagnosed with esophageal cancer. The purpose of this study was to assess the clinical efficacy and safety of proton beam therapy for older patients with esophageal cancer. Patients and methods. Older patients (age: ≥ 65 years) newly diagnosed with esophageal cancer between January 2009 and June 2013 were enrolled in this study. All patients underwent either proton beam therapy alone or proton beam therapy with initial X-ray irradiation. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results. Twenty patients were eligible for this study and all completed the treatment. The median age was 78 years (range: 65–89 years) and the median follow-up time was 26.5 months (range: 6–62 months). Seven patients had lymph node metastases and 10 had stage II/III cancer. The median dose of proton beam therapy was 72.6 Gy relative biological dose effectiveness (RBE) (range: 66–74.8 Gy [RBE]) for proton beam therapy alone and 33 Gy (RBE) (range: 30.8–39.6 Gy [RBE]; total dose range: 66.8–75.6 Gy [RBE]) for proton beam therapy with initial X-ray irradiation. The 2-year overall survival rate was 81.8% (95% confidence interval [CI]: 62.4%–100%), and the 2-year local control rate was 89.4% (95% CI: 75.5%–100%). Grade 2 or 3 toxicities occurred in some cases; however, no grade 4 or 5 toxicity was observed. Conclusions. High-dose (66–75.6 Gy [RBE]) proton beam therapy without chemotherapy was an efficacious and safe treatment for older patients with esophageal cancer.

scholarly journals Downregulation of Mcl-1 by Panobinostat Potentiates Proton Beam Therapy in Hepatocellular Carcinoma Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 554
Author(s):  
Changhoon Choi ◽  
Ga Haeng Lee ◽  
Arang Son ◽  
Gyu Sang Yoo ◽  
Jeong Il Yu ◽  
...  
Keyword(s):  
Proton Beam ◽  
Proton Irradiation ◽  
Apoptotic Cell ◽  
Relative Effectiveness ◽  
Hdac Inhibitors ◽  
Proton Beam Therapy ◽  
Clonogenic Survival ◽  
X Rays ◽  
Histone H4 ◽  
X Ray

Epigenetic modulation by histone deacetylase (HDAC) inhibitors is an attractive anti-cancer strategy for diverse hematological and solid cancers. Herein, we explored the relative effectiveness of the pan-HDAC inhibitor panobinostat in combination with proton over X-ray irradiation in HCC cells. Clonogenic survival assays revealed that radiosensitization of Huh7 and Hep3B cells by panobinostat was more evident when combined with protons than X-rays. Panobinostat increased G2/M arrest and production of intracellular reactive oxygen species, which was further enhanced by proton irradiation. Immunofluorescence staining of γH2AX showed that panobinostat enhanced proton-induced DNA damage. Panobinostat dose-dependently decreased expression of an anti-apoptotic protein, Mcl-1, concomitant with increasing acetylation of histone H4. The combination of panobinostat with proton irradiation enhanced apoptotic cell death to a greater extent than that with X-ray irradiation. Depletion of Mcl-1 by RNA interference enhanced proton-induced apoptosis and proton radiosensitization, suggesting a potential role of Mcl-1 in determining proton sensitivity. Together, our findings suggest that panobinostat may be a promising combination agent for proton beam therapy in HCC treatment.

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