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，大约有60,000名接受了近距离放射治疗。使用直接植入前列腺的微小放射性（0.1-10 MCI）钛种子进行前列腺近距离放射治疗（PB）。虽然磁共振成像（MRI）是前列腺和周围正常临界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种子在MRI上显示为黑洞（负面对比），并且不能准确地定位于前列腺和骨膜组织中。当前用于PB剂量法（超声检查，CT和荧光镜检查）的标准成像方式是次优的，质量保证（QA）已成为美国的主要问题。由于质量检查差，退伍军人管理局（VA）最近关闭了其四个前列腺牙治疗计划，导致治愈率降低和并发症的增加。使用次优成像，有时会无意间将过量剂量递送到尿液括约肌上。结果，大约8-10％的男性在PB后2年经历了尿液和尿失禁的泄漏。我们最近发明了由氯化钴（C4）组成的MRI标记物，该标记物可以准确地可视化PB中使用的植入的钛种子的MRI。 PI的小组一直积极开发和申请这项独特的技术，即“用于成像中使用的种子和标记”的国际专利申请。该STTR提案的最终目标是证明商业制造可植入的MRI标记的可行性。具体而言，该6个月计划的目标（第1阶段）是：（i）使用生物相容性聚合物材料制造MRI标记； （ii）前列腺幻象中MRI标记物的验证和优化。该提案具有创新性，因为使用C4 MRI标记是一种新型策略，它具有允许PB用于PROSTATE癌和其他类型癌症的MRI剂量测定法。 MRI-Visible近距离放射治疗标志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，并有可能导致美国超过200,000名男性的治疗范式转移。癌症治疗和消除尿失禁至关重要，将C4 MRI标记技术应用于PB的常规使用。在该项目过程中生产的C4 MRI标记将由Bard Brachtherapy Inc（总部位于新泽西州的20亿美元商业）评估，以作为PB链的间隔材料的潜在替代品和可能的许可。 C4 MRI标记对于前列腺，头颈，肺和胸枪治疗引起了极大的兴趣。 公共卫生相关性：该STTR提案的最终目标是证明商业植入可植入的C4 MRI标记的可行性。具体而言，该6个月计划的目标（第1阶段）是：（i）使用生物相容性聚合物材料制造C4 MRI标记； （ii）前列腺幻象中C4 MRI标记的验证和优化。 MRI-Visible近距离放射治疗C4标记的开发开发将满足提高PB剂量法的质量保证和国家标准化的关键需求。基于MRI的近距离放射治疗有可能导致每年诊断为局部前列腺癌的200,000多名男性的治疗范式转移。

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