SBIR-STTR Award

The goal of this project is to develop a quantitative molecular breast imaging PET (QMBI-PET) scanner to improve the way in which breast cancer therapies are matched to individual patients by providing evaluation of therapy efficacy during the window of opportunity between diagnosis and surgical resection. More than 250,000 women in the US with invasive disease start therapy for breast cancer each year. In 2016 approximately 40,000 deaths will result from breast cancer. 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. There are currently 68 FDA approved breast cancer drugs, the most of any cancer. PET holds great promise to improve therapy selection, thereby sparing patients from ultimately ineffective drugs and directing them more quickly to effective regimens, thus improving patient outcomes, and reducing costs via a more efficient therapy selection process. However, all of the studies thus far using PET to assess therapy response have been limited to the quantitative accuracy of clinical whole-body PET scanners A compact, lower-cost, high resolution, and quantitatively accurate PET imaging scanner will help inform the physician's choices of effective therapies for breast cancer patients. Early evaluation of a therapy's effectiveness will help the treating physician individualize a patient's treatment: In the neo-adjuvant setting or the window of opportunity between diagnosis and surgery, a baseline (pre-treatment) PET image will be taken, then, after a short regimen of a targeted therapy, a second PET scan will be used to evaluate response to treatment. This will be used to guide selection and aggressiveness of post-surgery therapy. For this treatment paradigm to become broadly accepted and widely used, the minimum viable commercial scanner needs to be higher resolution, more compact, and less expensive than standard whole-body PET scanners. In addition a high level of quantitative accuracy is needed. We propose a high-resolution quantitative molecular breast imaging PET (QMBI-PET) scanner, which uses a an advanced detector architecture and statistical-based 3D imaging to acquire high-sensitivity, high-resolution images. The outcome of this Phase-I application will be a functional laboratory tested single-ring prototype scanner, with initial data on clinical feasibility to provide evidence for commercialization in the following phase of this development.

Public Health Relevance Statement:
The goal of this project is to develop a commercially viable quantitative molecular breast imaging PET (QMBI- PET) scanner. This will improve the way in which breast cancer therapies are matched to individual patients by directing them more quickly to effective therapies, and will improve outcomes and reducing healthcare costs.

Project Terms:
Adjuvant; Adverse effects; Algorithms; Antineoplastic Agents; Architecture; attenuation; base; Breast; Breast Cancer Patient; Breast Cancer therapy; breast imaging; Caliber; Calibration; Cessation of life; Clinical; clinical application; commercialization; cost; Data; deep field survey; design; design and construction; detector; Development; Diagnosis; Disease; Dose; effective therapy; Effectiveness; Electronics; Evaluation; Excision; FDA approved; Goals; Health Care Costs; Image; Image Reconstructions; Imaging Phantoms; imaging system; improved; improved outcome; individual patient; ineffective therapies; innovation; Laboratories; Lesion; Letters; Link; Location; malignant breast neoplasm; Malignant Neoplasms; Mammary Neoplasms; Measures; Methods; Modeling; Molecular; molecular imaging; Neoadjuvant Therapy; Normal Statistical Distribution; novel; oncology; Operative Surgical Procedures; Outcome; Patient Care; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Phase; Phenotype; photomultiplier; Photons; Physicians; Platelet Factor 4; Positron-Emission Tomography; Process; prototype; quantitative imaging; Radiology Specialty; radiotracer; Regimen; Relapse; Resolution; response; Selection for Treatments; sensor; Side; Signal Transduction; Silicon; simulation; Source; Speed; Structure; success; System; targeted treatment; Testing; Thick; Three-Dimensional Imaging; Time; Treatment Efficacy; treatment response; tumor; uptake; Variant; Weight; Woman

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.

Public Health Relevance Statement:
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 reduce 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.

Project Terms:
Adjuvant Therapy; Algorithms; anatomic imaging; Antineoplastic Agents; base; Breast; breast cancer diagnosis; Breast Cancer Patient; Breast Cancer therapy; breast imaging; breast scanner; Caliber; Cancer Etiology; cancer therapy; cancer type; Cessation of life; Clinic; Clinical; Clinical Oncology; Clinical Trials; Clinical/Radiologic; commercialization; comparative; cost; cost effective; Data; design; detector; Development; Diagnosis; Disease; effective therapy; effectiveness evaluation; ERBB2 gene; Excision; FDA approved; fluorodeoxyglucose; Functional disorder; Future; Goals; Health Care Costs; human imaging; Image; image reconstruction; image registration; Imaging Phantoms; imaging system; Immunotherapy; improved; improved outcome; In complete remission; Individual; ineffective therapies; Injections; Laboratories; Left; Lesion; Letters; malignant breast neoplasm; Malignant neoplasm of lung; Malignant Neoplasms; Mammary Neoplasms; Mammography; Measures; Metabolic; Modality; Molecular; Molecular Biology; molecular imaging; Neoadjuvant Therapy; Operative Surgical Procedures; Outcome; Pathologic; Patient Care; Patient imaging; Patient-Focused Outcomes; Patients; Performance; PF4 Gene; Pharmaceutical Preparations; Phase; Phenotype; Positioning Attribute; Positron-Emission Tomography; Precision Medicine Initiative; prototype; quantitative imaging; Recommendation; Regimen; Relapse; Reporting; Reproducibility; resistance mechanism; Resolution; response; Roentgen Rays; Role; Selection for Treatments; sensor; Side; side effect; Source; standard of care; success; System; targeted treatment; Technology; Testing; Therapy Evaluation; therapy resistant; Time; tomosynthesis; Toxic effect; Tracer; Treatment Efficacy; treatment optimization; treatment response; tumor; United States National Institutes of Health; uptake; Variant; Woman; X-Ray Computed Tomography