Optimal drug release schedule for in-situ radiosensitization of image guided permanent prostate implants

Planned in-situ radiosensitization may improve the therapeutic ratio of image guided 125I prostate brachytherapy. Spacers used in permanent implants may be manufactured from a radiosensitizer-releasing polymer to deliver protracted localized sensitization of the prostate. Such devices will have a limited drug-loading capacity, and the drug release schedule that optimizes outcome, under such a constraint, is not known. This work determines the optimal elution schedules for 125I prostate brachytherapy. The interaction between brachytherapy dose distributions and drug distribution around drug eluting spacers is modeled using a linear-quadratic (LQ) model of cell kill. Clinical brachytherapy plans were used to calculate the biologic effective dose (BED) for planned radiation dose distributions while adding the spatial distributions of radiosensitizer while varying the temporal release schedule subject to a constraint on the drug capacity of the eluting spacers. Results: The greatest increase in BED is achieved by schedules with the greatest sensitization early in the implant. Making brachytherapy spacers from radiosensitizer eluting polymer transforms inert parts of the implant process into a means of enhancing the effect of the brachytherapy radiation. Such an approach may increase the therapeutic ratio of prostate brachytherapy or offer a means of locally boosting the radiation effect without increasing the radiation dose to surrounding tissues.