Fabrication and validation of implantable MRI markers for prostate cancer treatme

描述（由申请人提供）：每年诊断患有前列腺癌的200,000名男性中约有60,000人接受近距离治疗。前列腺近距离放射治疗（PB）是将放射性微小（0.1-10 mCi）的钛粒子直接植入前列腺。虽然磁共振成像（MRI）是前列腺及周围正常关键结构的最佳成像方式，但目前尚未用于PB，因为植入的放射性钛粒子在MRI上表现为黑洞（负对比），不能准确定位在前列腺和前列腺周围组织内。目前用于铅剂量测定的标准成像方式（超声、CT和透视）是次优的，质量保证（QA）在美国已成为一个主要问题。退伍军人管理局（VA）最近关闭了四个前列腺近距离治疗项目，原因是质量保证不佳，导致治愈率下降，并发症增加。由于成像不理想，过量的剂量有时会不经意地传递到尿括约肌。结果，大约8-10%的男性在PB后2年出现尿漏和尿失禁。我们最近发明了由氯化钴络合物（C4）组成的MRI标记物，可以在MRI上精确显示植入PB的钛种子。PI小组一直在积极开发和申请这项独特技术的专利，最近提交了“用于成像的种子和标记”的国际专利申请。这项STTR提案的最终目标是证明可植入MRI标记物商业化制造的可行性。具体来说，这个为期6个月的项目（第一阶段）的目标是：(i)使用生物相容性聚合物材料制造MRI标记物；（ii）前列腺幻像MRI标记物的验证和优化。这个建议是创新的，因为使用C4 MRI标记物是一种新的策略，它为前列腺癌和其他类型癌症的PB MRI剂量测定带来了巨大的希望。mri可见近距离放射治疗标记物的开创性发展将解决改善PB剂量学质量保证的关键需求，并有可能导致美国20多万男性治疗的范式转变。C4 MRI标志物技术在前列腺癌中的常规应用，对治疗癌症和消除尿失禁都有重要意义。该项目生产的C4 MRI标记物将由巴德近距离治疗公司（Bard Brachytherapy Inc .，总部位于新泽西州，年销售额20亿美元）评估，作为PB链间隔材料的潜在替代品，并可能获得许可。C4 MRI标记物在前列腺、头颈部、肺部和乳房近距离治疗中具有很大的兴趣，这是C4 Imaging有限责任公司最近成立的核心业务，旨在加快这些标记物的商业化。

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.