title: Brachytherapy application with in situ dose painting administered by gold nanoparticle eluters.
abstract: OBJECTIVE
  Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS).
  
  
  METHODS
  An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131).
  
  
  RESULTS
  Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125.
  
  
  CONCLUSIONS
  Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application with in situ dose painting administered via gold nanoparticle eluters for prostate cancer.
authors.affiliation: Department of Sciences, Wentworth Institute of Technology, Boston, Massachusetts.
authors.forename: Neeharika
authors.initials: N
authors.lastname: Sinha
authors.affiliation: Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Gizem
authors.initials: G
authors.lastname: Cifter
authors.affiliation: Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts.
authors.forename: Erno
authors.initials: E
authors.lastname: Sajo
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, Massachusetts.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, Massachusetts.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sridhar
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cormack
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: G Mike
authors.initials: GM
authors.lastname: Makrigiorgos
authors.affiliation: Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: wngwa@lroc.harvard.edu.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Ngwa
mesh_terms: D001918:Brachytherapy / Q000295:instrumentation / Q000379:methods*; D003198:Computer Simulation; D004343:Drug Implants / Q000737:chemistry / Q000627:therapeutic use*; D005240:Feasibility Studies; D006046:Gold / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D008954:Models, Biological; D009369:Neoplasms / Q000737:chemistry* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D014018:Tissue Distribution
chemical_list: D004343:Drug Implants; D006046:Gold