Radiotherapy Enhancement for Prostate Cancer Using Platinum-Based Nanoparticles
G Cifter1*, E Sajo2, G Makrigiorgos3, W Ngwa4, (1) University of Massachusetts, Lowell, Lowell, MA, (2) University of Massachusetts at Lowell, Lowell, MA, (3) Dana Farber Cancer Institute, Boston, MA, (4) Brigham & Woman's Hospital, Boston, MAWE-A-108-2 Wednesday 8:00AM - 9:55AM Room: 108
Purpose: In this work, the nucleus dose enhancement (nDEF) due to photoelectric interactions with cisplatin/oxaliplatin nanoparticles (CNPs/ONPs) is investigated in comparison to the nDEF due to gold nanoparticles (AuNPs) during prostate brachytherapy. CNPs/ONPs are particularly attractive since they may provide a more cost-effective alternative to AuNPs, but could also provide additional chemotherapy effect for prostate tumors.
Methods:As in previous studies, the dose enhancement to the PCa endothelial cells (EC) was determined using analytic microdosimetry calculations to determine the energy deposited in the EC nucleus due to radiation-induced photoelectrons emitted by the nanoparticles. Dividing the energy deposited by the mass of the nucleus yields the dose. The nDEF defined as the ratio of the overall dose to the nucleus with and without nanoparticles, was determined for a range of CNP and ONP concentrations up to the FDA approved limit, which is 1-34 mg/g and 1-50 mg/g for oxaliplatin and cisplatin, respectively.
Results:For Pd-103, the calculated nDEF due to photoelectrons alone was up to 2.4, and 2.3 for oxaliplatin, and cisplatin respectively, compared to over 3 for comparable concentrations of AuNPs. For I-125, the calculated nDEF was up to 1.95, and 1.8 for oxaliplatin, and cisplatin, respectively in comparison to 2.5 for comparable concentrations of AuNP.
Conclusion:The results predict that major localized dose enhancement to PCa cells can be achieved using targeted CNPs/ONPs. A potential application strategy for this result is to load routinely used brachytherapy spacers with such nanoparticles, which can then be sustainably released from within the tumor volume for photon-induced dose enhancement combined to the chemotherapy effect, with no increased toxicity to healthy tissue. Overall, the results motivate further work including: Monte Carlo work incorporating dose enhancement from Auger electrons, as well as corroborative experimental work towards development of this new application strategy.