Development of Smart INCeRT Brachytherapy Spacers via PLGA and Docetaxel for Combined Chemo-Radiation Therapies in Prostate Cancer
Mentor: Robert Cormack, Ph.D. (Dana Farber Cancer Institute)
Prostate cancer (PCa) is the second leading cause of cancer related deaths in men with 26,730 deaths and 161,360 new cases estimated in the US in 2017. Treatment options are scarce and often leave survivors with reduced quality of life due to off-target side effects. Radiation treatment in the form of permanent brachytherapy calls for the deposition of radioactive seeds in the prostate gland that release radiation overtime. Standard brachytherapy utilizes plastic inert spacers to obtain spatial guidance to place and separate radioactive seeds. Later stage PCa therapies include highly toxic and aggressive treatments such as systemic chemotherapy to control local progression and spreading of metastasis. Docetaxel (DTX), a chemotoxic agent via mitotic inhibition, is the primary drug used for chemotherapy treatments of PCa. In an effort to combine radiation therapy and chemotherapy to achieve targeted drug delivery and minimize toxicity levels, biodegradable “smart” spacers have been synthesized. These spacers are fabricated with a docetaxel loaded Poly(lactic-co-glycolic) acid (PLGA) cylindrical implant for intratumoral injection during brachytherapy procedures. Previous research has demonstrated the success of such spacers created from a mixture of PLGA, DTX and a solvent. In this project, methods to create solvent-free “smart” spacers are underway and require rheological and calorimetric analysis of the materials. Learned characteristics from these tests will enable us to successfully hot-melt extrude DTX loaded biocompatible spacers to be used in conjunction with radioactive seeds. Further research for this project regarding in vitro experiments and in vivo experiments in rodent models will help determine the synergistic affects of the combined chemo-radiation therapy (CRT) for tumors. The associated benefits of CRT compared to monotherapy require synchronization of the two modalities to achieve maximum benefit. The need to investigate novel PCa therapeutic strategies is immediate and will provide patients with higher survival rates, improve targeted drug delivery and avoid systemic toxicity.
On the left, a post-operative x-ray image of radioactive seeds placed during brachytherapy is shown. On the right, lab-synthesized “smart” INCeRT spacers containing the chemotoxic agent, Docetaxel, are displayed. The spacers provide clinicians with spatial and temporal guidance in order to approximately separate the radioactive seeds from one another and avoid ‘hot spots.’ Source: