Abstract 1473: Nanocoated brachytherapy spacers eluting radiosensitizers for biological in situ image-guided radiation therapy of prostate cancer

Abstract

Abstract The overall goal of this project is to develop means to locally radio-sensitize the prostate to enable prostate cancer (PCa) cure with the use of lower radiation doses, thereby leading to less rectal toxicity. This new approach for chemoradiation therapy (CRT), termed Biological In-Situ Image Guided Radiation Therapy BIS-IGRT, involves the coating of spacers routinely used during prostate I-125-based brachytherapy with radiosensitizing drugs (e.g. docetaxel DTX for PCa). This approach provides localized in-situ delivery of the sensitizer to the tumor and avoids the toxicity associated with current systemic delivery of radiosensitizers. BIS-IGRT adds radiosensitization capability to the standard brachytherapy procedure and with minimal additional inconvenience to the patient. Current CRT with adjuvant systemic chemotherapy does not provide the sustained delivery and drug concentration needed for efficient radiosensitization. Thereby BIS-IGRT improves the therapeutic ratio of radiation therapy without introducing additional patient interventions over current brachytherapy procedures. We have established the following: 1. We have shown through modeling that drug distributions can be achieved that can lead to increased efficiency of image-guided brachytherapy (drug-coated spacers) or image guided external beam therapy (drug-coated fiducials). 2. Doxorubicine-coated fiducials (Dox/PLGA-PEG/CHIT) show release characteristics over 40 days in aqueous media, which is tailored to the time scales required for BIS-IGRT. The cytotoxicity of Dox/ PLGA-PEG NP is comparable to that of free Dox, so that there is no reduction of activity upon encapsulation in the NP. 3. Localized bolus injection of dye-loaded PLGA-PEG nanoparticles (NPs) distributes within 24 hours throughout the tumor, indicating that the sustained release from coated brachytherapy spacers has the potential to achieve the desired biological dose-painting of the tumor. BIS-IGRT could proffer radiation oncologists and medical physicists with a new treatment option for substantially enhancing therapeutic ratio and boosting cure rate for the hundreds of thousands of Americans diagnosed with prostate cancer each year. This new treatment approach would be of crucial benefit for patients with local relapse who require salvage radiotherapy but have reached their radiotherapy normal tissue dose limits. BIS-IGRT can still be accompanied by IV administration of chemotherapeutics, particularly for micro-metastasis, so that existing therapeutic approaches are not compromised. In addition BIS-IGRT could potentially become a mainstream treatment for patients newly diagnosed with prostate or other cancers, where radiation therapy is a common treatment modality. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1473. doi:1538-7445.AM2012-1473