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Fluorescence-guided resection of breast tumors using a topically-applied molecular probe

使用局部应用分子探针进行荧光引导乳腺肿瘤切除术

基本信息

批准号：
10322725
负责人：
James Peter Basilion
金额：
$ 52.34万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10322725
关键词：
Academic Medical Centers Agreement Animals Breast Breast-Conserving Surgery Cancerous Carcinoma Cessation of life Clinical Clinical Trials Cosmetics Cyclic GMP Cytology Data Detection Development Diffusion Disease Distant Dose Drug Kinetics European Evaluation Excision FDA approved Fluorescence Fluorescent Probes Formalin Frozen Sections Goals Health Care Costs Home Hour Human Image Imaging Device Malignant Neoplasms Mammaplasty Mammary Neoplasms Mastectomy Maximum Tolerated Dose Methods Microscopic Molecular Probes Morbidity - disease rate Noninfiltrating Intraductal Carcinoma Operative Surgical Procedures Paraffin Embedding Pathologic Pathology Patients Peptide Hydrolases Performance Phase Postoperative Period Procedures Process Prognostic Factor Quality of life Radiation therapy Recurrence Repeat Surgery Residual Cancers Risk Risk Factors Safety Sampling Savings Signal Transduction Specimen Surface Surgeon Survival Rate Techniques Technology Testing Time Tissue Sample Tissues Topical application Touch sensation Toxicology Translating Translational Research Translations Tumor Tissue Vascularization Woman acute toxicity base breast lumpectomy cancer cell clinical application clinical imaging clinical translation experience first-in-human healthy volunteer image guided imager imaging agent imaging probe imaging study in vivo industry partner malignant breast neoplasm manufacturing facility molecular imaging mortality risk next generation novel novel strategies optical imaging pharmacokinetics and pharmacodynamics photonics preclinical imaging preclinical study prevent sample fixation screening standard of care success tumor

项目摘要

Project Summary/Abstract: Breast cancer is the most common cancer in women, with an estimated 246,660 cases (and 40,450 deaths) in the US during 2015. Due to better screening techniques cancers are caught earlier and 75% of patients are candidates for breast conserving surgery (BCS) to remove the cancer. BCS is cosmetically preferable to the alternative (mastectomy) and long-term survival rates are equivalent [1]. The success of BCS is assessed post-operatively by pathology. The status of the microscopic margins of excision of the lumpectomy specimen is still the most important prognostic and risk factor for local recurrence [2,3]. A positive margin indicates that invasive carcinoma or ductal carcinoma in situ is touching a tissue edge of a lumpectomy specimen. Among patients treated by BCS and radiation therapy, positive margins are associated with a 2-fold increase in the risk of local recurrence when compared with negative margins [4]. A finding of positive margins is estimated to occur between 8% to 86% of the time, requiring patients to return for further treatment often associated with poorer cosmetic results and increases in local and distant recurrence of the disease. Current pathology methods only assess about 1/10 of 1% of the entire volume of the removed specimen. A consequence of margin undersampling is that local recurrence occurs in 5-16% of patients with pathologically clean margins, suggesting that one or more regions of tumor had not been sampled during pathological analysis resulting in tumor remaining in the patient. In addition, there is still no universal agreement among breast surgeons on what constitutes an adequate negative margin for patients undergoing BCS [5]. Together these data demonstrate the unmet clinical need for technologies that rapidly and globally identify cancerous tissues in the surgical cavity and can be used to guide their surgical resections during the procedure. Molecular imaging guided resections of tumors during surgeries are now being developed. However, most approaches employ IV administration of optical imaging agents, which require hours or days to highlight tumor tissues. Moreover, infiltrating cancer cells in tissues surrounding the main mass may not have developed a vasculature and likely would not be identified using injected agents. Finally, illuminating the entire cancer mass may create a high background signal from tumor that is not “at the margin” of the lumpectomy. Exploiting increased protease expression at the edge of breast cancers we introduce the novel concept of in vivo topical administration of quenched fluorescent molecular imaging probes to identify cancer that may remain in the surgical cavity after standard-of-care resection. This builds on years of preclinical studies and seeks to characterize, perform toxicology, and finally a Phase 1A & B clinical trial to demonstrate the utility of this novel approach. It has the potential to reduce re-excisions as well as the false negative rate from pathology undersampling, with a consequent savings in healthcare costs and, enhancement in patient life quality.

项目摘要/摘要：乳腺癌是女性中最常见的癌症，估计有246660例