Fabrication and validation of implantable MRI markers for prostate cancer treatme

DESCRIPTION (provided by applicant): Approximately 60,000 of the 200,000 men diagnosed annually with prostate cancer are treated with brachytherapy. Prostate brachytherapy (PB) is performed using tiny radioactive (0.1-10 mCi) titanium seeds implanted directly into the prostate gland. While magnetic resonance imaging (MRI) is the best imaging modality for the prostate and surrounding normal critical structures, it is currently not used for PB because the implanted radioactive titanium seeds appear as black holes (negative contrast) on MRI and cannot be accurately localized within the prostate and periprostatic tissue. The current standard imaging modalities used for PB dosimetry (sonography, CT, and fluoroscopy) are suboptimal, and quality assurance (QA) has become a major problem in the US. The Veterans Administration (VA) has recently closed four of its prostate brachytherapy programs due to poor QA, leading to decrease cure rates and an increase in complications. With suboptimal imaging, excessive doses are sometimes inadvertently delivered to the urinary sphincters. As a result, approximately 8-10% of men experience leakage of urine and urinary incontinence at 2 years after PB. We recently invented MRI marker comprised of a cobalt chloride complex (C4) that allows accurate visualization on MRI of the implanted titanium seeds used in PB. The PI's group has been active in developing and patenting this unique technology-an international patent application for Seeds and Markers for Use in Imaging was recently filed. The ultimate goal of this STTR proposal is to demonstrate the feasibility of commercial fabrication of implantable MRI markers. Specifically, the goals of this 6-month program (Phase 1) are: (i) fabrication of MRI markers using biocompatible polymer materials; and (ii) validation and optimization of MRI markers in prostate phantoms. This proposal is innovative because the use of C4 MRI markers is a novel strategy that holds tremendous promise for permitting MRI dosimetry for PB for prostate cancer and also other types of cancer. The pioneering development of MRI-visible brachytherapy markers will address the critical need for improvement in quality assurance for PB dosimetry and has the potential to cause a paradigm shift in treatment for the over 200,000 men in the US. It is essential for both cancer cure and eliminating incontinence to apply C4 MRI marker technology to the routine use in PB. The C4 MRI markers produced in the course of this project will be evaluated by Bard Brachytherapy Inc ( 2- billion-annual business headquartered in New Jersey) as a potential substitute for spacer materials for PB strands and possible licensure. The C4 MRI markers are of great interest for prostate, head and neck, lung, and breast brachytherapy, the core business of the company recently founded to expedite commercialization of these markers, C4 Imaging, LLC. PUBLIC HEALTH RELEVANCE: The ultimate goal of this STTR proposal is to demonstrate the feasibility of commercial fabrication of implantable C4 MRI markers. Specifically, the goals of this 6-month program (Phase 1) are: (i) fabrication of C4 MRI markers using biocompatible polymer materials; and (ii) validation and optimization of C4 MRI markers in prostate phantoms. The pioneering development of MRI-visible brachytherapy C4 markers will address the critical need to improve quality assurance and national standardization of PB dosimetry. MRI-based brachytherapy has the potential to cause a paradigm shift in treatment for the over 200,000 men in the US diagnosed annually with localized prostate cancer.