Abstract
Purpose: A potential new therapeutic strategy to help prevent prostate cancer (PCa) recurrence involves loading routinely used brachytherapy spacers with non‐toxic/biocompatible radiosensitizing gold nanoparticles (GNPs), which can be sustainably released in situ for radiation boosting of high‐risk tumor subvolume. In this study, we investigated the intra‐tumor biodistribution and corresponding dose enhancement (DEF) over time for the released GNPs, as a function of nanoparticle size. Methods: An experimentally determined diffusion coefficient (D) for 10 nm nanoparticles in mouse PCa tumor model from previous studies 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 intratumor concentration profile for released GNPs from the spacer over time. The corresponding DEF profiles were then determined based on previously published results of DEF versus concentration when GNPs are employed during Pd‐103 and I‐125 brachytherapy. Results: As expected, the generated profiles showed greater DEF over time for smaller GNPs 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 (for average PCa tumor size of about 2 cm diameter) after 14, and 65 days, respectively for GNPs sizes 2 nm, and 10 nm, when treating with I‐125. Meanwhile for Pd‐103, clinically significant DEF could be achieved at the same position after 13, and 57 days, respectively, for 2 nm and 10 nm nanoparticles. Conclusion: Our preliminary results verify that intra‐tumor dose enhancement or sub‐volume boosting profiles can be customized by varying the sizes of nanoparticle released or eluted from nanoparticle‐loaded brachytherapy spacers. These results provide a useful reference for further studies towards development of Brachytherapy Application with in situ Dose‐painting Administered via Gold‐nanoparticle Eluters (BANDAGE) for prostate cancer.
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