MO‐FG‐BRA‐01: Development of An Image‐Guided Dosimetric Planning System for Injectable Brachytherapy Using ELP Nanoparticles

Purpose: To develop, validate, and evaluate a methodology for determining dosimetry for intratumoral injections of elastin‐like‐polypeptide (ELP) brachytherapy nanoparticles. These organic‐polymer‐based nanoparticles are injectable, biodegradable, and genetically tunable. We present a genetically encoded polymer‐solution, composed of novel radiolabeled‐ELP nanoparticles that are custom‐designed to self‐assemble into a local source upon intratumoral injection. Our preliminary results of a small animal study demonstrate 100% tumor response, effective radionuclide retention‐rates, strong in vivo stability, and no polymer‐induced toxicities. While our approach is therefore highly promising for improved brachytherapy, the current workflow lacks a dosimetry framework. Methods: We are developing a robust software framework that provides image‐guided dosimetric‐planning capabilities for ELP brachytherapy. The user graphically places ELP injection sites within a µCT‐planning‐image, and independently defines each injection volume, concentration, and radioisotope to be used. The resulting internal dosimetry is then pre‐determined by first modeling post‐injection ELP advection‐diffusion, and then calculating the resulting dose distribution based on a point‐ dose‐kernel‐convolution algorithm. We have experimentally measured ELP steady‐state concentrations via µSPECT acquisition, and validated our dose calculation algorithm against Monte Carlo simulations of several radioactivity distributions. Finally, we have investigated potential advantages and limitations of various ELP injection parameters. Results: The µSPECT results demonstrated inhomogeneous steady‐state distributions of ELP in tissue, and Monte Carlo radioactivity distributions were designed accordingly. Our algorithm yielded a root‐mean‐square‐error of less than 2% for each distribution tested (average root‐mean‐square‐error was 0.73%). Dose‐Volume‐Histogram analysis of five different plans showed how strategic injection placement, and an injection volume‐tapering technique, could be used to achieve D95% target coverage. Conclusion: We have preliminarily developed a novel planning framework for ELP brachytherapy. Its dosimetry accuracy has been validated against Monte Carlo, and we have started to investigate the potential advantages of injection‐based planning. This system, once fully developed, will serve as the technical foundation for our novel approach.