A pH Responsive Transistor-like Nanoprobe for Sensitive Detection of Unknown Primary Cancers of the Head and Neck

pH 响应型晶体管纳米探针，用于灵敏检测头颈部未知原发性癌症

• 批准号: 10631041
• 负责人: Baran D Sumer
• 金额: $ 56.05万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631041
• 关键词: Acidosis; Address; Adjuvant Therapy; Aerodigestive Tract; Avidity; Basement membrane; Biopsy; Blood Vessels; Cancer Detection; Cancer Patient; Caring; Cells; Chemotherapy and/or radiation; Clinical; Darkness; Data; Detection; Endoscopes; Epithelium; Excision; FDA approved; Fluorescence; Freezing; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Histologic; Histology; Histopathology; Human Papillomavirus; Image; Impairment; Indocyanine Green; Inflammatory; Intravenous; Libraries; Light; Lymphatic; Lymphoid Tissue; Malignant Neoplasms; Malignant neoplasm of pharynx; Mediating; Micelles; Modality; Mucous Membrane; Nature; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Pathology; Patient-Focused Outcomes; Patients; Pharyngeal structure; Phase; Phase II Clinical Trials; Phase Transition; Physical Examination; Polymers; Positron-Emission Tomography; Primary Neoplasm; Prognosis; Quality-Adjusted Life Years; Sensitivity and Specificity; Serious Adverse Event; Staging; Stains; Surface; Tail; Testing; Time; Tissues; Tonsil; Tonsillar Tissue; Tonsillectomy; Transistors; Validation; Veins; X-Ray Computed Tomography; amphiphilicity; aqueous; cancer diagnosis; detection sensitivity; fluorodeoxyglucose; functional improvement; head and neck cancer patient; human tissue; improved; in vivo fluorescence; intravenous administration; intravenous injection; invention; lymph nodes; lymphocyte proliferation; meter; millimeter; nanoprobe; optimal treatments; overtreatment; standard of care; targeted treatment; tumor; tumor microenvironment; viral detection

A pH Responsive Transistor-like Nanoprobe for Sensitive Detection of Unknown Primary Cancers of the Head and Neck Project Summary/Abstract Approximately 65,000 cases of Head and Neck Squamous Cell Cancer (HNSCC) are diagnosed each year in the US and arise in the mucosal lining of the upper aerodigestive tract and spread to local lymph nodes. In some cases, the primary tumor is too small to be detected, with enlarged nodes being the only manifestation of HNSCC. These unknown primary cancers (UPCs), often induced by human papilloma virus (HPV), usually arise in the mucosa of Waldeyer's ring, the lymphatic tonsillar tissues of the pharynx. Finding UPC is significant and impactful addressing an unmet need with long term oncologic and functional outcomes improved by locating and removing UPC. However, their detection is impaired by the corrugated, cryptic surface, and nodularity of lymphatic tissue which decreases the sensitivity of physical examination while the vascularity and fluorodeoxyglucose (FDG) avidity of the lymphoid tissue obscure small tumors by computerized tomography (CT) and positron emission tomography (PET). We have invented a library of ultra pH sensitive (UPS) nanoprobes, covalently conjugated to indocyanine green (ICG) that respond to acidic tumor microenvironment, with a concomitant sharp change in their fluorescence state from OFF to ON. One such nanoprobe, ONM-100, has been developed and studied in a Phase 1 and ongoing FDA approved Phase 2 clinical trial. it has been shown to be well tolerated with no serious adverse events, compatible with surgical endoscopes, and able to detect a variety of cancers including HNSCC in real time. Based on these data we hypothesize that ONM-100 used as an adjunct to SOC panendoscopy can improve detection of UPC. To test our hypothesis, we will (1) Compare the sensitivity and specificity of activatable probe ONM-100 for cancer detection to always ON probes for tumors in Waldeyer's ring; (2) Detect HPV-mediated HNSCC in patients after systemic administration of ONM-100 comparing fluorescence to true-positive cancers; (3) Detect UPC in patients after systemic administration of ONM-100. Successful execution of this project will provide precise excision of UPC and avoidance of intense adjuvant therapy for UPC patients significantly improving care and outcomes for these patients who suffer greatly from less oncologically effective imprecise overtreatment.

用于灵敏检测未知初级的 pH 响应型晶体管纳米探针 头颈癌 项目概要/摘要 大约 65,000 例头颈鳞状细胞癌 (HNSCC) 在美国每年都会被诊断出来，并出现在上呼吸消化道的粘膜内层 并扩散至局部淋巴结。在某些情况下，原发肿瘤太小而无法检测到， 淋巴结肿大是 HNSCC 的唯一表现。这些未知的原发癌症 (UPC)，通常由人乳头瘤病毒 (HPV) 诱导，通常出现在韦氏粘膜中 环，咽部的淋巴扁桃体组织。寻找 UPC 意义重大且具有影响力 解决未满足的需求，通过定位改善长期肿瘤和功能结果 并删除 UPC。然而，它们的检测受到波纹、神秘表面和 淋巴组织结节，降低体检的敏感性 淋巴组织的血管分布和氟脱氧葡萄糖（FDG）亲和力掩盖了小肿瘤 计算机断层扫描（CT）和正电子发射断层扫描（PET）。 我们发明了一个超 pH 敏感 (UPS) 纳米探针库，共价结合到 吲哚菁绿（ICG）对酸性肿瘤微环境做出反应，并伴随着尖锐的 它们的荧光状态从关闭变为开启。一种这样的纳米探针，ONM-100，已被 在第一阶段和正在进行的 FDA 批准的第二阶段临床试验中开发和研究。它一直 表现出良好的耐受性，没有严重的不良事件，与手术内窥镜兼容， 能够实时检测包括 HNSCC 在内的多种癌症。根据这些数据我们 假设 ONM-100 用作 SOC 全内窥镜的辅助装置可以改善对以下疾病的检测： 统一产品代码。为了检验我们的假设，我们将 (1) 比较可激活的敏感性和特异性 用于癌症检测的探针 ONM-100 始终开启 Waldeyer 环中肿瘤的探针； (2) 全身给药 ONM-100 后检测患者中 HPV 介导的 HNSCC 比较 荧光检测真阳性癌症； (3) 全身给药后患者的UPC检测 ONM-100。该项目的成功执行将提供UPC的精确切除和避免 UPC 患者的强化辅助治疗显着改善了这些患者的护理和结果 因肿瘤学效果较差、不精确的过度治疗而遭受严重痛苦的患者。