Tumor Vasculature Dose-Painting with FDA Approved Concentrations of Cisplatin, Oxaliplatin, and Carboplatin Nanoparticles During External Beam Radiotherapy
W Ngwa1*, Y Altundal2, E Sajo3, G Makrigiorgos4, R Berbeco5, (1) Brigham & Woman's Hospital, Boston,, MA, (2) University of Massachusetts at Lowell, Lowell, MA, (3) University of Massachusetts at Lowell, Lowell, MA, (4) Dana Farber Cancer Institute, Boston, MA, (5) Brigham and Women's Hospital, Boston, MAWE-E-108-2 Wednesday 2:00PM - 3:50PM Room: 108
Purpose: Recent studies have cogently demonstrated major dose enhancement to tumor endothelial cells (EC) when targeted with gold nanoparticles (GNPs) during external beam radiotherapy (EBR). This study investigates the endothelial dose enhancement for FDA approved concentrations of platinum-based nanoparticles: cisplatin nanoparticles (CNPs), Oxaliplatin nanoparticles (ONPs) and carboplatin nanoparticles (CBNPs) as potential alternative to GNPs.
Methods: As in previous work for GNPs, analytic calculations were carried out to estimate the dose to the EC caused by radiation-induced photoelectrons from platinum nanoparticles during EBR. Here, Monte Carlo generated 6 MVp energy spectra at depth of 20 cm (10 x 10 cm2 field) was employed. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the EC with and without the presence of nanoparticles was calculated. The result was then appropriately scaled to reflect the percentage of platinum in CNPs, ONPs, and CBNPs. For the first time, the investigated concentration range took into account a potential clinical scenario where the nanoparticles are released in situ from routinely used fiducials loaded with the nanoparticles.
Results: As expected, the results showed increase in EDEF with increased concentration of the nanoparticles for both GNPs and platinum NPs, with the highest contribution to the EDEF coming from the lower kV-energy part of the EBR beam spectrum. At FDA concentration limits of in situ released nanoparticles results revealed EDEF values of up to ca. 1.8 for 60 mg/g CNPs, 1.6 for 50 mg/g ONPs and 2.2 for 120 mg/g CBNPs.
Conclusions: The results predict that substantial photon-induced dose boost to tumor endothelial cells can be achieved by applying tumor vasculature-targeted CNPs, ONPs or CBNPs during external beam radiotherapy. Such radiation boosting or vasculature dose painting could be customized to work complementarily with the chemotherapy effect of these nanoparticles for more effective treatment outcomes.