Brachytherapy in situ dose-painting administered via gold-nanoparticle eluters

通过金纳米颗粒洗脱器进行近距离放射治疗原位剂量涂抹

• 批准号: 9326917
• 负责人: Wilfred Ngwa
• 金额: $ 17.71万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-17 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9326917
• 关键词: 3-Dimensional; Award; Biodistribution; Biological; Blood; Brachytherapy; Brachytherapy Seeds; Cancer Patient; Clinical; Clinical Research; Custom; Dana-Farber Cancer Institute; Development; Diffusion; Dose; Drug Kinetics; Electrons; Environment; Faculty; Film; Fluorescence; Goals; Gold; Human; Implant; In Situ; International; LNCaP; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Methods; Mission; Modality; Mus; Nanotechnology; Neoplasm Metastasis; Normal tissue morphology; Nude Mice; Outcome; Patients; Photons; Polymers; Positioning Attribute; Pre-Clinical Model; Prior Therapy; Productivity; Prostate; Prostatic Neoplasms; Publications; Quality of life; Radiation; Radiation therapy; Radiation-Sensitizing Agents; Rectum; Recurrence; Relapse; Research; Research Personnel; Resources; Salvage Therapy; Software Tools; Source; Stream; Therapeutic; Time; Tissues; Toxic effect; Training; Tumor Volume; Urethra; Work; X-Ray Computed Tomography; Xenograft procedure; biomaterial compatibility; cancer recurrence; cancer therapy; career; career development; cohort; controlled release; design; dosimetry; experience; fight against; high risk; implantation; improved; in vivo; innovation; medical schools; minimal risk; mouse model; nanoparticle; predictive tools; prevent; programs; prostate cancer model; public health relevance; radioresistant; radiosensitizing; research and development; tool; treatment choice; treatment planning; treatment site; tumor

DESCRIPTION (provided by applicant): The candidate has demonstrated great potential to successfully transition into independence as evinced by his research productivity, high quality of research publications, awards, and honors. His immediate career goal is to develop the new BANDAGE for prostate cancer treatment approach and successfully transition into independence. His long term goal is to develop an internationally recognized research program in applications of nanotechnology in radiation therapy. The KO1 award will provide protected time for carrying out the proposed research and complementary didactic and clinical training components Environment: The institutional environment, Dana-Farber Cancer Institute (DFCI), Harvard Medical School is optimally suitable for conducting the proposed research and career development of the candidate. The necessary didactic, clinical and research resources are available together with key faculty to work with. Research: The overall goal of the proposed research is to develop a new brachytherapy application with in situ dose-painting administered via gold-nanoparticle eluters (BANDAGE) that would circumvent current critical barriers to salvage radiotherapy and radiation boosting for prostate cancer. BANDAGE seeks to circumvent these critical limitations by loading routinely used brachytherapy spacers with radio-sensitizing (but) biocompatible gold nanoparticles (AuNP), which can be released/eluted in situ after implantation in prostate tumors. The AuNP release, in situ, from the spacers and consequent 3-dimensional intra-tumor bio-distribution over time may be customized e.g. by varying AuNP size, spacer position, concentration, and other parameters to provide sub-volume AuNP-aided radiation boosting of the prostate without increased toxicity to healthy tissue. The central hypothesis of this K01 application is that the new BANDAGE for prostate cancer treatment modality is a more efficacious approach for salvage radiotherapy and radiation boosting, because of the potential for customizable sub-volume boosting without increase in normal tissue toxicity. The specific aims are: 1) Establish customizable intra-tumor biodistribution profiles and pharmacokinetics of gold nanoparticles (AuNP) released from gold-loaded brachytherapy spacers in pre-clinical models; 2) Demonstrate significant therapeutic enhancement using BANDAGE in preclinical models; 3) Develop treatment planning software tools for BANDAGE for prostate cancer. Relevant to the mission of the NCI, the expected outcomes of this project include: development of potentially improved treatment option (BANDAGE) for prostate cancer patients, and career development of the applicant into a successful and productive independent investigator in the fight against cancer.

描述（由申请人提供）：候选人表现出成功过渡到独立的巨大潜力，这通过他的研究生产力、高质量的研究出版物、奖项和荣誉得到证明。他近期的职业目标是开发新的 BANDAGE 前列腺癌治疗方法并成功过渡到独立。他的长期目标是开发国际认可的纳米技术在放射治疗中的应用研究项目。 KO1 奖将为开展拟议的研究以及补充性的教学和临床培训部分提供受保护的时间。 环境：哈佛医学院 Dana-Farber 癌症研究所 (DFCI) 的机构环境非常适合开展拟议的研究和职业发展。候选人。我们提供必要的教学、临床和研究资源以及与之合作的主要教师。研究：拟议研究的总体目标是开发一种新的近距离放射治疗应用，通过金纳米颗粒洗脱器（BANDAGE）进行原位剂量涂抹，从而规避当前前列腺癌挽救性放射治疗和增强放射治疗的关键障碍。 BANDAGE 试图通过在常规使用的近距离放射治疗垫片上装载放射增敏（但）生物相容性金纳米粒子（AuNP）来规避这些关键限制，这些金纳米粒子可以在植入前列腺肿瘤后原位释放/洗脱。 AuNP 从间隔物中原位释放以及随后随时间推移的 3 维肿瘤内生物分布可以定制，例如通过改变 AuNP 尺寸、间隔物位置、浓度和其他参数，可提供亚体积 AuNP 辅助的前列腺辐射增强，而不增加对健康组织的毒性。该 K01 应用的中心假设是，用于前列腺癌治疗方式的新 BANDAGE 是挽救性放射治疗和增强辐射的更有效方法，因为它具有可定制的子体积增强而不增加正常组织毒性的潜力。具体目标是： 1）在临床前模型中建立可定制的肿瘤内生物分布曲线和金纳米粒子（AuNP）从载金近距离放射治疗垫片释放的药代动力学； 2) 在临床前模型中证明使用 BANDAGE 具有显着的治疗增强作用； 3) 开发前列腺癌 BANDAGE 治疗计划软件工具。与 NCI 的使命相关，该项目的预期成果包括：为前列腺癌患者开发潜在改进的治疗方案 (BANDAGE)，以及将申请人的职业发展为抗击癌症的成功且富有成效的独立研究者。

项目成果

Nanoparticle-aided external beam radiotherapy leveraging the Čerenkov effect.

• DOI: 10.1016/j.ejmp.2016.06.015
• 发表时间: 2016-07
• 期刊: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)
• 作者: Ouyang Z;Liu B;Yasmin-Karim S;Sajo E;Ngwa W
• 通讯作者: Ngwa W

A Software App for Radiotherapy with In-situ Dose-painting using high Z nanoparticles.

• DOI: 10.1007/978-3-319-19387-8_151
• 发表时间: 2015-06
• 期刊: IFMBE proceedings
• 作者: Jermoumi M;Yucel A;Hao Y;Cifter G;Sajo E;Ngwa W
• 通讯作者: Ngwa W

Radiation Oncology Solutions in Tanzania.

坦桑尼亚的放射肿瘤学解决方案。

• DOI: 10.1016/j.ijrobp.2015.08.043
• 发表时间: 2015
• 期刊: International journal of radiation oncology, biology, physics
• 作者: Avery,Stephen;Kenton,Owen;binDachi,Jumaa;Metz,James;Ngwa,Wilfred
• 通讯作者: Ngwa,Wilfred

Smart Radiation Therapy Biomaterials.

• DOI: 10.1016/j.ijrobp.2016.10.034
• 发表时间: 2017-03-01
• 期刊: International journal of radiation oncology, biology, physics
• 作者: Ngwa W;Boateng F;Kumar R;Irvine DJ;Formenti S;Ngoma T;Herskind C;Veldwijk MR;Hildenbrand GL;Hausmann M;Wenz F;Hesser J
• 通讯作者: Hesser J

Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation.

• DOI: 10.1088/0031-9155/60/18/7035
• 发表时间: 2015-09-21
• 期刊: Physics in medicine and biology
• 影响因子: 3.5
• 作者: Hao Y;Altundal Y;Moreau M;Sajo E;Kumar R;Ngwa W
• 通讯作者: Ngwa W