A Sparse-readout Quantitative PET scanner for breast cancer therapy optimization

用于优化乳腺癌治疗的稀疏读数定量 PET 扫描仪

• 批准号: 10080314
• 负责人: William Coulis Jason Hunter
• 金额: $ 123.11万
• 依托单位: PET/X, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-29 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080314
• 关键词: Adjuvant Therapy; Algorithms; Antineoplastic Agents; Breast; Breast Cancer Patient; Breast Cancer therapy; Caliber; Cancer Etiology; Cessation of life; Clinic; Clinical; Clinical Oncology; Clinical Trials; Clinical/Radiologic; Data; Development; Diagnosis; Disease; ERBB2 gene; Excision; FDA approved; Functional disorder; Future; Goals; Health Care Costs; Image; Imaging Phantoms; Immunotherapy; In complete remission; Individual; Injections; Laboratories; Left; Lesion; Letters; Malignant Neoplasms; Malignant neoplasm of lung; Mammary Neoplasms; Mammography; Measures; Metabolic; Modality; Molecular; Molecular Biology; Neoadjuvant Therapy; Operative Surgical Procedures; Outcome; PF4 Gene; Pathologic; Patient Care; Patient imaging; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Phase; Phenotype; Positioning Attribute; Positron-Emission Tomography; Precision Medicine Initiative; Recommendation; Regimen; Relapse; Reporting; Reproducibility; Resolution; Roentgen Rays; Role; Selection for Treatments; Side; Source; System; Technology; Testing; Therapy Evaluation; Time; Toxic effect; Tracer; Treatment Efficacy; United States National Institutes of Health; Variant; Woman; X-Ray Computed Tomography; anatomic imaging; base; breast cancer diagnosis; breast imaging; breast scanner; cancer therapy; cancer type; commercialization; comparative; cost; cost effective; design; detector; effective therapy; effectiveness evaluation; fluorodeoxyglucose; human imaging; image reconstruction; image registration; imaging system; improved; improved outcome; ineffective therapies; malignant breast neoplasm; molecular imaging; prototype; quantitative imaging; resistance mechanism; response; sensor; side effect; standard of care; success; targeted treatment; therapy resistant; tomosynthesis; treatment optimization; treatment response; tumor; uptake

Our goal is to improve how breast cancer therapies are matched to individual breast-cancer patients with early- stage disease by providing a timely evaluation of therapy efficacy during the window of opportunity between diagnosis and surgical resection. In so doing, we aim to direct patients more quickly to effective therapies, improving outcomes, and reducing toxicities and healthcare costs from ineffective treatments. We will achieve this goal by developing a commercially viable, quantitative molecular breast imaging system (the PET/X scanner) that combines synergistically with mammography or tomosynthesis systems in breast imaging clinics. Breast cancer is the most common type of cancer found in US women and is the second leading cause of cancer death among women after lung cancer. Substantial progress has been made in treating breast cancer due to the use of targeted therapies. Unfortunately, despite the successes of targeted therapies the relapse rate in patients expressing the targets and receiving these therapies still approaches 50% for certain phenotypes. The drugs can be very costly and carry toxic side effects. Selecting from the 69 FDA approved breast cancer drugs (the most of any cancer) is challenging. A test to provide a rapid and direct measure of therapy response in each patient, or lack thereof, would greatly benefit patient care by matching patients to drugs with demonstrated success against their disease. The selection of therapies that optimize patient outcomes is a cornerstone of both the NIH precision medicine initiative and recommendations from the NCI Cancer Moonshot report. Positron emission tomography (PET) has a demonstrated ability to improve therapy selection. However, PET studies thus far using whole-body (WB) PET scanners to assess therapy response are limited to a lesion size greater than 2 cm to be quantitatively accurate. This is a challenge for breast cancer as a majority of patients present with early stage disease in which the lesions are smaller than 2 cm. To enable this treatment paradigm a PET scanner needs to be much more compact and less expensive than WB PET scanners and support correlative anatomical imaging. In addition, a high level of quantitative accuracy is needed. To meet these criteria, we will use the cost-effective dual-sided position-sensitive sparse sensor (DS-PS3) technology developed in Phase-I to build a viable PET system for the breast cancer window-of- opportunity response assessment task. The PET scanner is compatible with x-ray mammography or tomosynthesis, forming a dual-modality PET/X scanner system. We will then assess quantitative performance of this prototype with phantom images and we will acquire proof-of-concept patient images. The outcome of this Phase-2 application will be a clinic-ready prototype scanner that will be used to assess clinical feasibility and to acquire preliminary human-image data needed as evidence to warrant full commercial development and provide data for planning a clinical trial and regulatory submissions.

我们的目标是改善乳腺癌治疗如何与早期乳腺癌患者个体相匹配， 通过在以下时间段的机会窗内提供治疗疗效的及时评估， 诊断和手术切除。通过这样做，我们的目标是更快地指导患者接受有效的治疗， 改善结果，减少无效治疗的毒性和医疗费用。我们将实现 通过开发商业上可行的定量分子乳腺成像系统（PET/X 扫描仪），其与乳房成像诊所中的乳房X射线照相术或断层合成系统协同组合。 乳腺癌是美国女性中最常见的癌症类型，也是导致乳腺癌的第二大原因。 女性肺癌后的癌症死亡率。治疗乳腺癌取得了实质性进展 因为使用了靶向治疗。不幸的是，尽管靶向治疗取得了成功， 表达靶点并接受这些治疗的患者中， 表型这些药物可能非常昂贵，并带有毒副作用。从69个FDA批准的 乳腺癌药物（所有癌症中最具挑战性的）。一种快速直接测量 每个患者的治疗反应或缺乏治疗反应，将通过将患者与 已经证明对他们的疾病有效的药物。选择优化患者的治疗方法 结果是NIH精确医学倡议和NCI建议的基石 癌症登月报告。 正电子发射断层扫描（PET）已被证明能够改善治疗选择。然而，PET 迄今为止，使用全身（WB）PET扫描仪评估治疗反应的研究仅限于病变大小 大于2 cm的尺寸，则定量准确。这对大多数乳腺癌患者来说是一个挑战， 存在早期疾病，其中病变小于2 cm。 为了实现这种治疗范例，PET扫描仪需要比常规PET扫描仪更紧凑且更便宜。 WB PET扫描仪，支持相关解剖成像。此外，高水平的定量准确性 是必要的。为了满足这些标准，我们将使用具有成本效益的双面位置敏感稀疏传感器 （DS-PS3）技术在第一阶段开发，以建立一个可行的PET系统，用于乳腺癌窗口期， 机会反应评估任务。PET扫描仪与X射线乳腺摄影兼容， 断层合成，形成双模态PET/X扫描仪系统。然后，我们将评估量化绩效 这个原型的幻象图像，我们将获得概念验证患者图像。 第二阶段应用的结果将是一个临床就绪的原型扫描仪， 临床可行性，并获得所需的初步人体图像数据，作为保证完全商业化的证据 开发和提供数据以规划临床试验和监管申报。