title: Modeling gold nanoparticle-eluting spacer degradation during brachytherapy application with in situ dose painting.
abstract: OBJECTIVE
  To investigate the dosimetric impact of slow vs burst release of gold nanoparticles (GNPs) from biodegradable brachytherapy spacers loaded with GNPs, which has been proposed to increase therapeutic efficacy during brachytherapy application with in situ dose painting.
  
  
  METHODS
  Mathematical models were developed based on experimental data to study the release of GNPs from a spacer designed with poly(lactic-co-glycolic acid) polymer. The models addressed diffusion controlled-release process and poly(lactic-co-glycolic acid) degradation kinetics that were used to determine GNP concentration profiles in tumour and the corresponding dose enhancement.
  
  
  RESULTS
  The results show a significant delay of GNP diffusion in the tumour in comparison to burst release assumed in previous studies. The model for diffusion controlled-release process and the model for combined processes of both diffusion and polymer degradation indicated that it may take about 25 and 45 days, respectively, for all GNPs to release from the spacer. Based on tumour concentration profiles, a significant dose enhancement factor (>2) could be attained at a tumour distance of 5 mm from a spacer loaded with 2-, 5- and 10-nm GNP sizes.
  
  
  CONCLUSIONS
  The results highlight the need to account for the slow release of GNPs from spacers and polymer biodegradation in research development of the GNP-eluting spacers. The findings suggest the use of radioisotopes with longer half-lives, such as iodine-125, in comparison with others with shorter half-lives such as Pd-103 and Cs-131. Advances in knowledge: The study provides a scientific platform and basis for research development of GNP-eluting spacers that can be used during brachytherapy to boost dose to tumour subvolumes, towards enhancing therapeutic efficacy. It concludes that the use of iodine-125 would be more feasible.
authors.affiliation: 1 Department of Biomedical Engineering and Biotechnology, University of Massachusetts, Lowell, MA, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Boateng
authors.affiliation: 1 Department of Biomedical Engineering and Biotechnology, University of Massachusetts, Lowell, MA, USA.|2 Department of Physics and Applied Physics, University of Massachusetts, Lowell, MA, USA.|3 Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Ngwa
mesh_terms: D001918:Brachytherapy / Q000295:instrumentation / Q000379:methods*; D003198:Computer Simulation; D004343:Drug Implants / Q000494:pharmacology*; D006046:Gold / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid; D053768:Metal Nanoparticles; D008962:Models, Theoretical; D009369:Neoplasms / Q000532:radiotherapy*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011874:Radiometry; D011879:Radiotherapy Dosage; D014018:Tissue Distribution
chemical_list: D004343:Drug Implants; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006046:Gold