In Vitro Dose Enhancement From Gold Nanoparticles During Low-dose-rate Gamma Irradiation With I-125 Brachytherapy Seeds page 1

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

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  • they are used for fast image acquisition or advanced techniques such as

    dose enhancement factor (DEF), representing the ratio of the dose to

    the cells with and without the presence of AuNP, was estimated fromvirtual native scans and bone removal. But they also provide new ways

    for a better tissue characterization. The latter is especially needed in

    proton and ion radiation therapy where uncertainties in the CT calibration

    jeopardize the potential of high accuracy treatment delivery. When tissues

    deviate significantly from water-equivalency (or standard tissue),

    a single CT number fails as quantifier for proton/ion range. Metal

    implants aggravate the situation considerably by being highly non-tissue

    equivalent or by inducing severe imaging artifacts. This even leads to the

    rejection of patients. Therefore, our study investigates the possible

    benefits of DECT for proton and ion radiation therapy treatment

    planning.

    Materials/Methods: DECT scans with two different photon spectra wereused to compute the electron density and effective atomic number of tissue

    surrogates and materials with elevated atomic number. Furthermore,

    preclinical reconstruction algorithms with extended CT range and raw data

    based beam hardening correction were used for imaging artifact correction

    and an improved geometrical characterization. We scanned a series of

    tissue equivalent materials, polymers and metal samples in a second

    generation DECT scanner. A novel CT data calibration was established,

    which relates both DECT parameters to measured ions ranges (270 MeV/u

    Carbon).

    Results: We extracted the electron densities and effective atomic numbersof the measured materials. Using this additional information, a better

    material differentiation was feasible. Furthermore, we were able to

    correlate the effective atomic number to the mean ionization energy which

    is crucial for the ion range estimation of materials with higher atomic

    number. This allowed us to improve the WEPL predictions not only for

    tissue equivalent, but also for non tissue-equivalent materials such PMMA

    (from -6.7% to 1%) and Aluminum (11.3% deviation from theoretical

    value, which may be further improved). The reconstruction algorithms

    used in this study impact the assessment of geometry and artifacts of metal

    implants.

    Conclusions: DECT imaging offers additional tissue information that canenhance ion range calculations in materials with non standard elemental

    composition. It can provide better geometrical information on metal

    implants with less noise and artifacts.

    Author Disclosure: C. Tremmel: None. N. Huenemohr: None. B. Krauss:

    A. Employee; Siemens AG. H. Schlemmer: None. O. Jaekel: None. S.

    Greilich: None.

    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

    S. Sridhar,4 M. Makrigiorgos,1 and R.A. Cormack1; 1Brigham and

    Womens Hospital, Dana-Farber Cancer Institute and Harvard Medical

    School, Boston, MA, 2Dana-Farber Cancer Institute and Harvard Medical

    School, Boston, MA, 3Harvard Medical School, Boston, MA, 4Northeastern

    University, Boston, MA

    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

    and S. Greilich1; 1German Cancer Research Center (DKFZ), Medical

    Physics in Radiation Oncology, Heidelberg, Germany, 2Siemens AG,

    Healthcare Sector, Imaging and Therapy Division, Forchheim, Germany,3University Hospital of Heidelberg, Radiation Oncology and Radiation

    Therapy, Heidelberg, Germany

    Purpose/Objective(s): Dual energy computed tomography (DECT)scanners are increasingly available in the clinic today. Most commonly,

    S134adjuvants to radiation therapy at kV energies. Because the enhancementthe data.

    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

    to 2.3 times greater than without AuNP. This major increase in radiation

    damage to cancer cells incubated with AuNP corresponds to an estimated

    DEF of over 3.5.

    Conclusions: Our findings provide the first experimental evidence ofsubstantial dose enhancement from gold nanoparticles during low dose rate

    gamma irradiation from brachytherapy sources. These in vitro study results

    provide impetus for further preclinical and clinical investigations in the

    development of gold nanoparticle-aided brachytherapy.

    Author Disclosure: W. Ngwa: None. H. Korideck: None. A. Kimmelman:

    None. A.I. Kassis: None. R. Kumar: None. S. Sridhar: None. M. Makri-

    giorgos: None. R.A. Cormack: None.

    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;

    University of Iowa, Iowa City, IA

    Purpose/Objective(s): We propose using a temperature-sensitivehydroGEL to allow clinicians to perform direct needle-based injection of

    micro-size radiation therapy (RT)-sources for localized tumors (RT-GEL).

    RT-GEL allows clinicians to perform direct needle-based injection of

    micro-size radioactive-sources for localized tumors. For instance, it can

    be used for initially not-lumpectomy eligible breast tumor as a form of

    neoadjuvant chemotherapy and concurrent RT-GEL boost or for localized

    liver cancer.

    Materials/Methods: The hydrogel is liquid at room temperature butalmost immediately gels at body temperature. It was generated as an

    injectable vehicle to deliver micro-size radioactive-sources by

    synthesizing two FDA-approved polymers, Pluronic F-127 (BASF,

    Gurney, USA) and animal-free sodium hyaluronate (SH, Shiseido,

    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

    In111 on the characteristics of hydrogel was tested. The injectability

    and efficacy of RT-GEL delivery to human breast tumor using the

    control datasets of RT-Saline injection were also tested. As proof-of-results from processes at kV energies, some studies proposed gold nano-

    particle-aided brachytherapy as a radiation therapy approach with potential

    to meet technical and clinical requirements for implementation. To the best

    of our knowledge, there has been no study providing clear experimental

    evidence to corroborate the substantial dose enhancement predictions

    when irradiating with low dose rate gamma photons from brachytherapy

    sources. This study investigates the in vitro dose enhancement of AuNP

    during irradiation of cancer cells by I-125 low dose rate brachytherapy

    sources.

    Materials/Methods: HeLa cell cultures were incubated with andwithout gold nanoparticles (AuNP) in alternate wells of an 8 well-

    chamber slide; 4 wells on each slide had cell cultures with AuNP

    while 4 wells contained cell cultures with no AuNP. Two slides were

    prepared for each experiment: one slide to be irradiated while the

    other serves as sham-irradiation control. The cells were irradiated with

    gamma photons from I-125 brachytherapy seeds in a plaque contained

    in a custom-built irradiation jig. The plaque was designed to achieve

    a relatively homogeneous dose distribution in the plane of the cell

    culture slide. Four sets of irradiation experiments were conducted at

    370C at dose rates ranging from 2.1 cGy/hr to 4.5 cGy/hr. The dose

    rates were varied by varying the height of the cell culture slide above

    the plaque containing the I-125 seeds. Residual gammaH2AX was

    measured 24 hours after irradiation and used to compare the dose

    response of the cells with and without AuNP. In addition, the relative

    International Journal of Radiation Oncology Biology Physicsconcept studies, a total 6 nude mice were tested in which 4 million

    Dual Energy CT: Treatment Planning for Proton and Ion Radiation Therapy Beyond Standard Tissue CompositionPurpose/Objective(s)Materials/MethodsResultsConclusions

    In Vitro Dose Enhancement From Gold Nanoparticles During Low-dose-rate Gamma Irradiation With I-125 Brachytherapy SeedsPurpose/Objective(s)Materials/MethodsResultsConclusions

    Local Targeted Delivery of Micro-size Radiation Therapy-source Using Temperature-sensitive Hydrogel (RT-GEL)Purpose/Objective(s)Materials/Methods