Abstract
Purpose:Replacing routinely used brachytherapy spacers with multifunctional ones loaded with cisplatin nanoparticles (CNP), which can be released into the tumor after implantation, could enable customizable radiation boosting to the prostate tumor in addition to chemotherapy effect. This study investigates the feasibility of customizing the intra‐tumor biodistribution and corresponding dose enhancement (DEF) over time for the released CNP as a function of nanoparticle size.Methods:Dose enhancement factors (DEF) due to photon‐induced emission of photo‐/Auger electrons from CNPs were calculated as a function of concentration using previously published analytical calculation method. An experimentally determined diffusion coefficient (D) for 10 nm nanoparticles in mouse tumor model was employed to estimate D for other sizes using the Stoke‐ Einstein equation. The error function diffusion model in the experimental study was applied to generate the intra‐tumor concentration profile for a burst release of CNPs from the spacer over time. The corresponding DEF profiles were then determined for brachytherapy using Pd‐103 and I‐125 sources.Results:As expected, the generated profiles showed greater DEF over time for smaller CNP sizes at sample distances from the spacer. For example, for a centrally located spacer, clinically significant DEF (> 20%) could be achieved near the tumor periphery (ca. 0.85 cm distance from the spacer for average PCa tumor size) after 20, and 100 days, respectively for CNPs sizes of 2 nm, and 10 nm, using I‐125. Meanwhile for Pd‐103, clinically significant DEF could be achieved at the same position after 22 and 108 days, respectively, for same size particles.Conclusion:Our preliminary results demonstrate the feasibility of customizing dose enhancement to prostate tumors as a function of spacer location, brachytherapy source type or size of CNPs released from multifunctional spacers. Such an approach could enable customizable radiation boosting to tumor sub‐volumes, while minimizing dose to healthy tissues.
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