Fabrication and validation of implantable MRI markers for prostate cancer treatme

用于前列腺癌治疗的植入式 MRI 标记物的制造和验证

• 批准号: 7999684
• 负责人: Andrew Bright
• 金额: $ 15.58万
• 依托单位: C4 IMAGING, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7999684
• 关键词: Address; Adverse effects; Affect; Aftercare; Agar; Biocompatible; Biocompatible Materials; Biological Sciences; Bladder Control; Body Temperature; Brachytherapy; Breast; Businesses; Cancer Center; Cancer Model; Cancer Survivor; Chemicals; Clinical; Clinical Research; Complex; Contrast Media; Custom; Development; Devices; Diagnosis; Dose; Dysuria; Effectiveness; Encapsulated; Engineering; Environment; Erectile dysfunction; Evaluation; Extravasation; Figs - dietary; Fluoroscopy; Future; Gland; Goals; Head; Head and neck structure; Heating; Hemorrhage; High temperature of physical object; I125 isotope; Image; Imagery; Imaging Techniques; Implant; Incidence; Incontinence; International; Lead; Legal patent; Length; Licensing; Licensure; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Marketing; Mechanics; Methods; Modification; Morphologic artifacts; New Jersey; Noise; Normal tissue morphology; Notification; Organ; Palladium; Palladium 103; Performance; Periprostatic; Phase; Physicians; Polymers; Positioning Attribute; Predisposition; Problem Solving; Procedures; Process; Production; Property; Prostate; Prostatic Neoplasms; Protocols documentation; Quality of life; Radiation; Radiation Oncology; Radiation therapy; Radioactive; Radioisotopes; Relative (related person); Research; Research Ethics Committees; Robot; Robotics; Safety; Science; Seed Implantation; Seeds; Signal Transduction; Small Business Technology Transfer Research; Solutions; Sphincter; Standardization; Structure; System; Technology; Time; Tissues; Titanium; Tube; Ultrasonics; Ultrasonography; United States; United States Department of Veterans Affairs; Universities; University of Texas M D Anderson Cancer Center; Urinary Incontinence; Urine; Validation; Weight; Work; X-Ray Computed Tomography; base; biocompatible polymer; biomaterial compatibility; cancer type; cobaltous chloride; commercialization; cost; design; dosimetry; experience; imaging modality; improved; innovation; interest; interstitial; irradiation; large scale production; manufacturing process; men; minimally invasive; novel; novel strategies; phase 1 study; phase 2 study; polyetheretherketone; prevent; professor; programs; public health relevance; quality assurance; radiofrequency; rectal; scale up; seal; treatment planning; urinary; verification and validation; vibration

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.

描述（由申请人提供）：每年诊断为前列腺癌的200，000名男性中约有60，000人接受近距离放射治疗。前列腺近距离放射治疗（PB）使用直接植入前列腺的微小放射性（0.1-10 mCi）钛粒子进行。虽然磁共振成像（MRI）是前列腺和周围正常关键结构的最佳成像方式，但目前不用于PB，因为植入的放射性钛粒子在MRI上显示为黑洞（负对比度），无法准确定位在前列腺和前列腺周围组织内。目前用于PB剂量测定的标准成像模式（超声、CT和荧光透视）是次优的，质量保证（QA）已成为美国的主要问题。退伍军人管理局（VA）最近关闭了四个前列腺近距离放射治疗项目，由于质量保证不佳，导致治愈率下降和并发症增加。在次优成像的情况下，过量的剂量有时会无意中输送到尿道括约肌。结果，大约8-10%的男性在PB后2年出现漏尿和尿失禁。我们最近发明了由氯化钴复合物（C4）组成的MRI标记物，可在MRI上准确显示PB中使用的植入钛粒子。PI的团队一直在积极开发这项独特的技术并为其申请专利-最近提交了一项国际专利申请“用于成像的种子和标记”。本STTR提案的最终目标是证明植入式MRI标记商业制造的可行性。具体而言，该6个月项目（第1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;以及（ii）在前列腺体模中验证和优化MRI标记物。该提议是创新的，因为C4 MRI标记物的使用是一种新的策略，其对于允许用于前列腺癌以及其他类型的癌症的PB的MRI剂量测定具有巨大的希望。MRI可见近距离放射治疗标记物的开创性开发将解决改善PB剂量测定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。将C4 MRI标记技术应用于PB的常规应用，对于癌症的治疗和消除尿失禁都是至关重要的。Bard Brachytherapy Inc（总部位于新泽西，年营业额20亿美元）将对本项目过程中生产的C4 MRI标记物进行评价，作为PB股线垫片材料的潜在替代品，并可能获得许可。C4 MRI标记物对前列腺、头颈部、肺和乳腺近距离放射治疗非常感兴趣，这是最近成立的公司C4 Imaging，LLC的核心业务，旨在加快这些标记物的商业化。 公共卫生相关性：本STTR提案的最终目标是证明植入式C4 MRI标记的商业制造的可行性。具体而言，该6个月项目（第1阶段）的目标是：（i）使用生物相容性聚合物材料制造C4 MRI标记物;以及（ii）在前列腺体模中验证和优化C4 MRI标记物。MRI可见近距离放射治疗C4标记物的开创性发展将解决改善PB剂量测定的质量保证和国家标准化的迫切需要。基于MRI的近距离放射治疗有可能导致美国每年诊断患有局限性前列腺癌的20多万男性的治疗模式转变。

项目成果

Permanent prostate brachytherapy postimplant magnetic resonance imaging dosimetry using positive contrast magnetic resonance imaging markers.

使用正对比磁共振成像标记进行永久性前列腺近距离放射治疗植入后磁共振成像剂量测定。

• DOI: 10.1016/j.brachy.2017.04.004
• 发表时间: 2017
• 期刊: Brachytherapy
• 影响因子: 1.9
• 作者: Martin,GeoffreyV;Pugh,ThomasJ;Mahmood,Usama;Kudchadker,RajatJ;Wang,Jihong;Bruno,TeresaL;Bathala,Tharakeswara;Blanchard,Pierre;Frank,StevenJ
• 通讯作者: Frank,StevenJ