In Vitro Dose Enhancement From Gold Nanoparticles During Low-dose-rate Gamma Irradiation With I-125 Brachytherapy Seeds

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<ul><li><p>they are used for fast image acquisition or advanced techniques such as</p><p>dose enhancement factor (DEF), representing the ratio of the dose to</p><p>the cells with and without the presence of AuNP, was estimated fromvirtual native scans and bone removal. But they also provide new ways</p><p>for a better tissue characterization. The latter is especially needed in</p><p>proton and ion radiation therapy where uncertainties in the CT calibration</p><p>jeopardize the potential of high accuracy treatment delivery. When tissues</p><p>deviate significantly from water-equivalency (or standard tissue),</p><p>a single CT number fails as quantifier for proton/ion range. Metal</p><p>implants aggravate the situation considerably by being highly non-tissue</p><p>equivalent or by inducing severe imaging artifacts. This even leads to the</p><p>rejection of patients. Therefore, our study investigates the possible</p><p>benefits of DECT for proton and ion radiation therapy treatment</p><p>planning.</p><p>Materials/Methods: DECT scans with two different photon spectra wereused to compute the electron density and effective atomic number of tissue</p><p>surrogates and materials with elevated atomic number. Furthermore,</p><p>preclinical reconstruction algorithms with extended CT range and raw data</p><p>based beam hardening correction were used for imaging artifact correction</p><p>and an improved geometrical characterization. We scanned a series of</p><p>tissue equivalent materials, polymers and metal samples in a second</p><p>generation DECT scanner. A novel CT data calibration was established,</p><p>which relates both DECT parameters to measured ions ranges (270 MeV/u</p><p>Carbon).</p><p>Results: We extracted the electron densities and effective atomic numbersof the measured materials. Using this additional information, a better</p><p>material differentiation was feasible. Furthermore, we were able to</p><p>correlate the effective atomic number to the mean ionization energy which</p><p>is crucial for the ion range estimation of materials with higher atomic</p><p>number. This allowed us to improve the WEPL predictions not only for</p><p>tissue equivalent, but also for non tissue-equivalent materials such PMMA</p><p>(from -6.7% to 1%) and Aluminum (11.3% deviation from theoretical</p><p>value, which may be further improved). The reconstruction algorithms</p><p>used in this study impact the assessment of geometry and artifacts of metal</p><p>implants.</p><p>Conclusions: DECT imaging offers additional tissue information that canenhance ion range calculations in materials with non standard elemental</p><p>composition. It can provide better geometrical information on metal</p><p>implants with less noise and artifacts.</p><p>Author Disclosure: C. Tremmel: None. N. Huenemohr: None. B. Krauss:</p><p>A. Employee; Siemens AG. H. Schlemmer: None. O. Jaekel: None. S.</p><p>Greilich: None.</p><p>332In Vitro Dose Enhancement From Gold Nanoparticles During Low-dose-rate Gamma Irradiation With I-125 Brachytherapy SeedsW. Ngwa,1 H. Korideck,2 A. Kimmelman,2 A.I. Kassis,3 R. Kumar,4</p><p>S. Sridhar,4 M. Makrigiorgos,1 and R.A. Cormack1; 1Brigham and</p><p>Womens Hospital, Dana-Farber Cancer Institute and Harvard Medical</p><p>School, Boston, MA, 2Dana-Farber Cancer Institute and Harvard Medical</p><p>School, Boston, MA, 3Harvard Medical School, Boston, MA, 4Northeastern</p><p>University, Boston, MA</p><p>Purpose/Objective(s): Recent studies have predicted substantial doseenhancement to tumors when gold nanoparticles (AuNP) are employed as331Dual Energy CT: Treatment Planning for Proton and Ion RadiationTherapy Beyond Standard Tissue CompositionC. Tremmel,1 N. Huenemohr,1 B. Krauss,2 H. Schlemmer,1 O. Jaekel,3,1</p><p>and S. Greilich1; 1German Cancer Research Center (DKFZ), Medical</p><p>Physics in Radiation Oncology, Heidelberg, Germany, 2Siemens AG,</p><p>Healthcare Sector, Imaging and Therapy Division, Forchheim, Germany,3University Hospital of Heidelberg, Radiation Oncology and Radiation</p><p>Therapy, Heidelberg, Germany</p><p>Purpose/Objective(s): Dual energy computed tomography (DECT)scanners are increasingly available in the clinic today. Most commonly,</p><p>S134adjuvants to radiation therapy at kV energies. Because the enhancementthe data.</p><p>Results: From the dose response behavior, the results show that the bio-logic effect when irradiating with 0.2 mg/mL concentration of AuNP is up</p><p>to 2.3 times greater than without AuNP. This major increase in radiation</p><p>damage to cancer cells incubated with AuNP corresponds to an estimated</p><p>DEF of over 3.5.</p><p>Conclusions: Our findings provide the first experimental evidence ofsubstantial dose enhancement from gold nanoparticles during low dose rate</p><p>gamma irradiation from brachytherapy sources. These in vitro study results</p><p>provide impetus for further preclinical and clinical investigations in the</p><p>development of gold nanoparticle-aided brachytherapy.</p><p>Author Disclosure: W. Ngwa: None. H. Korideck: None. A. Kimmelman:</p><p>None. A.I. Kassis: None. R. Kumar: None. S. Sridhar: None. M. Makri-</p><p>giorgos: None. R.A. Cormack: None.</p><p>333Local Targeted Delivery of Micro-size Radiation Therapy-sourceUsing Temperature-sensitive Hydrogel (RT-GEL)Y. Kim, D. Seol, S. Mohapatra, M.K. Schultz, F.E. Domann, and T. Lim;</p><p>University of Iowa, Iowa City, IA</p><p>Purpose/Objective(s): We propose using a temperature-sensitivehydroGEL to allow clinicians to perform direct needle-based injection of</p><p>micro-size radiation therapy (RT)-sources for localized tumors (RT-GEL).</p><p>RT-GEL allows clinicians to perform direct needle-based injection of</p><p>micro-size radioactive-sources for localized tumors. For instance, it can</p><p>be used for initially not-lumpectomy eligible breast tumor as a form of</p><p>neoadjuvant chemotherapy and concurrent RT-GEL boost or for localized</p><p>liver cancer.</p><p>Materials/Methods: The hydrogel is liquid at room temperature butalmost immediately gels at body temperature. It was generated as an</p><p>injectable vehicle to deliver micro-size radioactive-sources by</p><p>synthesizing two FDA-approved polymers, Pluronic F-127 (BASF,</p><p>Gurney, USA) and animal-free sodium hyaluronate (SH, Shiseido,</p><p>Japan). Indium-111 (T1/2 Z 2.8 days, primary gamma ray 862keV)was tested as a micro-size radioactive source. The radiation effect of</p><p>In111 on the characteristics of hydrogel was tested. The injectability</p><p>and efficacy of RT-GEL delivery to human breast tumor using the</p><p>control datasets of RT-Saline injection were also tested. As proof-of-results from processes at kV energies, some studies proposed gold nano-</p><p>particle-aided brachytherapy as a radiation therapy approach with potential</p><p>to meet technical and clinical requirements for implementation. To the best</p><p>of our knowledge, there has been no study providing clear experimental</p><p>evidence to corroborate the substantial dose enhancement predictions</p><p>when irradiating with low dose rate gamma photons from brachytherapy</p><p>sources. This study investigates the in vitro dose enhancement of AuNP</p><p>during irradiation of cancer cells by I-125 low dose rate brachytherapy</p><p>sources.</p><p>Materials/Methods: HeLa cell cultures were incubated with andwithout gold nanoparticles (AuNP) in alternate wells of an 8 well-</p><p>chamber slide; 4 wells on each slide had cell cultures with AuNP</p><p>while 4 wells contained cell cultures with no AuNP. Two slides were</p><p>prepared for each experiment: one slide to be irradiated while the</p><p>other serves as sham-irradiation control. The cells were irradiated with</p><p>gamma photons from I-125 brachytherapy seeds in a plaque contained</p><p>in a custom-built irradiation jig. The plaque was designed to achieve</p><p>a relatively homogeneous dose distribution in the plane of the cell</p><p>culture slide. Four sets of irradiation experiments were conducted at</p><p>370C at dose rates ranging from 2.1 cGy/hr to 4.5 cGy/hr. The dose</p><p>rates were varied by varying the height of the cell culture slide above</p><p>the plaque containing the I-125 seeds. Residual gammaH2AX was</p><p>measured 24 hours after irradiation and used to compare the dose</p><p>response of the cells with and without AuNP. In addition, the relative</p><p>International Journal of Radiation Oncology Biology Physicsconcept studies, a total 6 nude mice were tested in which 4 million</p><p>Dual Energy CT: Treatment Planning for Proton and Ion Radiation Therapy Beyond Standard Tissue CompositionPurpose/Objective(s)Materials/MethodsResultsConclusions</p><p>In Vitro Dose Enhancement From Gold Nanoparticles During Low-dose-rate Gamma Irradiation With I-125 Brachytherapy SeedsPurpose/Objective(s)Materials/MethodsResultsConclusions</p><p>Local Targeted Delivery of Micro-size Radiation Therapy-source Using Temperature-sensitive Hydrogel (RT-GEL)Purpose/Objective(s)Materials/Methods</p></li></ul>


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