Development of a Novel Peptide Platform for Targeted PET Imaging and Radiotherapy of Breast Cancer

开发用于乳腺癌靶向 PET 成像和放射治疗的新型肽平台

基本信息

批准号：
9763552
负责人：
Lukas Michael Carter
金额：
$ 6.37万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-18 至 2020-09-17
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9763552
关键词：
4T1 90Y Acidity Affect Affinity Analytical Chemistry Area Biodistribution Breast Cancer Model Breast Cancer Treatment Breast Cancer therapy Cancer Biology Cancerous Career Choice Cell membrane Cellular Membrane Chelating Agents Cleaved cell Clinic Clinical Communities Complement Cyclotrons Daughter Development Diagnosis Diagnostic Distant Dose ERBB2 gene Educational workshop Exhibits Fellowship Foundations Functional disorder Future Goals Grant Image Individual National Research Service Award Institution International Isotopes Knowledge Label Lead Malignant Neoplasms Mammary Neoplasms Memorial Sloan-Kettering Cancer Center Mentors Modality Modeling Molecular Mus Nature Patient Care Peptides Pharmacologic Substance Positron-Emission Tomography Prediction of Response to Therapy Public Speaking Radiation therapy Radioactive Radiochemistry Radioisotopes Radiology Specialty Radionuclide Generators Radiopharmaceuticals Research Research Design Research Personnel Research Project Grants Resources Site Solid Staging Syringes System Technology Testing Therapeutic Therapeutic Uses Tissues Toxic effect Training Translational Research Treatment Efficacy Twin Multiple Birth United States Variant Woman Work Writing analog animal-assisted therapy anticancer research base cancer cell career development clinical application computational chemistry design ds-DNA experience extracellular fluorodeoxyglucose imaging agent improved in vivo in vivo evaluation innovation malignant breast neoplasm neoplastic cell novel oncology outcome forecast patient population portability post-doctoral training pre-clinical professor student mentoring targeted agent targeted treatment theranostics tool trait treatment response triple-negative invasive breast carcinoma tumor tumor microenvironment virtual

项目摘要

Project Summary/Abstract The PI is committed to the development of novel tools for the diagnosis and treatment of breast cancer, with a short-term objective to gain impactful and necessary training and a long-term commitment towards a career path in breast cancer radiology and oncology. The PI recently joined the community of dedicated cancer researchers at Memorial Sloan Kettering Cancer Center (MSK) as a postdoctoral research scholar in the Lab of Professor Jason S. Lewis, an internationally renowned expert in PET probe development and translational science. The Advising Committee, comprised of a Primary Mentor (Lewis) and Co-Mentors (Drs. Weber and Morris) and PI have identified specific areas in cancer biology, pathophysiology, and radiology which the PI will need to further develop to establish himself as an independent researcher; they have cooperatively formulated a plan for training and development. The proposed F32 training plan outlines a set of career development activities and workshops—including grant writing, public speaking, lab management, and mentoring students— designed to enhance the PI’s ability to be an independent investigator. The PI’s choice of sponsors, research project, and training will provide a solid foundation to reach his present and future academic and professional goals (please see Biosketches and Facilities & Resources). Breast cancer remains the most common cancer among women in the United States, with approximately 12% of women developing breast cancer over the course of her lifetime. 10-20% of this patient population is affected by triple-negative breast cancer (TNBC), a subtype with particularly poor prognosis in part due to the lack of effective targeted therapies. The Lewis Lab has developed a pH(low) insertion peptide (pHLIP®), which targets tissues with increased extracellular acidity—a hallmark of virtually all cancerous tissue—through cellular membrane insertion. Affinity of pHLIP® for this universally exhibited tumoral trait highlights its potential for use in oncologic clinical applications, and in particular for TNBC, as pHLIP® targeting is unaffected by the absence of ER, PR, and HER2 characterized by TNBC. Therefore, the objective of this project is multifaceted: a) to optimize pHLIP® for use as a general diagnostic tool with generator-produced radiometals in an effort to decouple clinics from the need for a neighboring cyclotron, b) to extend the clinical applications of pHLIP® to targeted therapy and theranostics for TNBC, c) to develop a novel 225Ac-based pHLIP® radiobioconjugate for targeted α-therapy of TNBC, and finally, d) to make a lasting contribution to patient care through the development of a motivated, independent investigator committed to the conquest of cancer.

项目概要/摘要 PI 致力于开发用于乳腺癌诊断和治疗的新工具，获得有效且必要的培训以及对职业生涯的长期承诺的短期目标 PI 最近加入了乳腺癌放射学和肿瘤学领域。纪念斯隆凯特琳癌症中心 (MSK) 的研究人员作为实验室的博士后研究学者国际知名 PET 探针开发和转化专家 Jason S. Lewis 教授咨询委员会由主要导师（刘易斯）和联合导师（韦伯博士和 Morris）和 PI 已经确定了癌症生物学、病理生理学和放射学的特定领域，PI 将需要进一步发展以确立自己作为独立研究者的地位；培训和发展计划拟议的 F32 培训计划概述了一套职业发展计划。活动和研讨会——包括资助写作、公开演讲、实验室管理和指导学生—— 旨在增强 PI 成为独立研究者的能力 PI 选择赞助商、研究。项目和培训将为他现在和未来的学术和专业发展奠定坚实的基础目标（请参阅生物草图以及设施和资源）。乳腺癌仍然是美国女性最常见的癌症，约占 12% 10-20% 的女性在其一生中罹患乳腺癌。受三阴性乳腺癌 (TNBC) 影响，该亚型的预后特别差，部分原因是缺乏有效的靶向疗法 Lewis 实验室开发了一种 pH（低）插入肽 (pHLIP®)，靶向细胞外酸度增加的组织（几乎所有癌组织的标志） pHLIP® 对这种普遍表现出的肿瘤特征的亲和力凸显了其潜力。用于肿瘤临床应用，特别是 TNBC，因为 pHLIP® 靶向不受缺乏以 TNBC 为特征的 ER、PR 和 HER2 因此，该项目的目标是多方面的： a) 优化 pHLIP®，将其用作发生器产生的放射性金属的通用诊断工具，以期将诊所与邻近回旋加速器的需求分离，b) 将 pHLIP® 的临床应用扩展到 TNBC 的靶向治疗和治疗诊断学，c) 开发一种新型的基于 225Ac 的 pHLIP® 放射性生物共轭物 TNBC 的靶向 α 疗法，最后，d) 通过以下方式为患者护理做出持久贡献：培养一位积极主动、独立的研究者，致力于征服癌症。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

PARaDIM: A PHITS-Based Monte Carlo Tool for Internal Dosimetry with Tetrahedral Mesh Computational Phantoms.

PARaDIM：基于 PHITS 的蒙特卡罗工具，用于使用四面体网格计算模型进行内部剂量测量。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Carter, Lukas M;Crawford, Troy M;Sato, Tatsuhiko;Furuta, Takuya;Choi, Chansoo;Kim, Chan Hyeong;Brown, Justin L;Bolch, Wesley E;Zanzonico, Pat B;Lewis, Jason S
通讯作者：
Lewis, Jason S

MIRD Pamphlet No. 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry.

MIRD 小册子第 28 号，第 1 部分：MIRDcalc-A 用于医疗内辐射剂量测定的软件工具。

DOI：
发表时间：
2023-07
期刊：
影响因子：
0
作者：
Kesner, Adam L;Carter, Lukas M;Ramos, Juan C Ocampo;Lafontaine, Daniel;Olguin, Edmond A;Brown, Justin L;President, Bonnie;Jokisch, Derek W;Fisher, Darrell R;Bolch, Wesley E
通讯作者：
Bolch, Wesley E

The Impact of Positron Range on PET Resolution, Evaluated with Phantoms and PHITS Monte Carlo Simulations for Conventional and Non-conventional Radionuclides.

正电子范围对 PET 分辨率的影响，通过体模和 PHITS 蒙特卡罗模拟对常规和非常规放射性核素进行评估。

DOI：
发表时间：
2020
期刊：
影响因子：
3.1
作者：
Carter, L M;Kesner, Adam Leon;Pratt, E C;Sanders, V A;Massicano, A V F;Cutler, C S;Lapi, S E;Lewis, Jason S
通讯作者：
Lewis, Jason S

Technical Note: Patient-morphed mesh-type phantoms to support personalized nuclear medicine dosimetry - a proof of concept study.

技术说明：患者变形的网状模型支持个性化核医学剂量测定 - 概念验证研究。