Abstract 4917: Smart brachytherapy spacers eluting nanoencapsulated radiosensitizers for chemo-radiation therapy

Abstract

Abstract Introduction: We have developed a new approach for chemoradiation therapy (CRT), termed Biological In-Situ Image Guided Radiation Therapy BIS-IGRT, which involves the coating of spacers routinely used during prostate I-125-based brachytherapy with radiosensitizing drugs (e.g. docetaxel DTX and gold nanoparticles). 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 providing sustained delivery and drug concentration and with minimal additional inconvenience to the patient. Thereby BIS-IGRT improves the therapeutic ratio of radiation therapy without introducing additional patient interventions over current brachytherapy procedures. Methods: We have fabricated a nanoparticles based smart ‘INCeRT’ (Implantable Nanoplatform for Chemo-Radiation Therapy) implant for localized delivery of radiosensitizing nanoparticles/ drugs in prostate cancer in conjunction with brachytherapy. These implants are physically similar to the clinically used brachytherapy spacers but have the added capability of imaging and local drug delivery. We have fabricated INCeRT spacers with biocompatible and biodegradable polymer, PLGA impregnated with nanoparticles encapsulating imaging probe (Cyanine 7.5) and chemotherapeutic drug, docetaxel (DTX). Using a similar approach, we have also fabricated PLGA spacers impregnated with high Z (atomic number) gold nanoparticles (Hi-Z-CuRE: High Z-Customizable Radiotherapy Enhancement) for effectively boosting the radiation dose locally. The morphology, composition and nanoparticle's distribution inside the spacers was studied by SEM (scanning electron microscopy) and EDS (Energy-dispersive X-ray spectroscopy). Further, preliminary in vivo imaging experiments with subcutaneous prostate cancer tumored mice implanted with INCeRT spacers showed a size dependent diffusion of nanoparticles from the spacers in the tumor matrix. Also, from in vivo therapeutic studies with these spacers showed a sustained and slow release of the DTX from the spacers and showed a better response in suppressing the tumor as opposed to control mice with saline injections. Further experiments for studying the combined chemo-radiation therapy are underway. Conclusions: BIS-IGRT is a powerful approach 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 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. This work was supported partially by NSF-DGE-0965843, HHS/1U54CA151881 CORE1, 1R03 CA164645-01 and a seed grant from the BWH Biomedical Research Institute. Note: This abstract was not presented at the meeting. Citation Format: Rajiv Kumar, Jodi Belz, Stacey Markovic, Mark Niedre, Wilfred Ngwa, Houari Korideck, Robert Cormack, Paul Nguyen, Anthony D'Amico, Mike Makrigiorgos, Srinivas Sridhar. Smart brachytherapy spacers eluting nanoencapsulated radiosensitizers for chemo-radiation therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4917. doi:10.1158/1538-7445.AM2014-4917