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Non-Invasive Detection of Tumor Extracellular pH using Multispectral Optoacoustic Tomography

使用多光谱光声断层扫描非侵入性检测肿瘤细胞外 pH 值

基本信息

批准号：
10251935
负责人：
Lacey R McNally
金额：
$ 32.11万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251935
关键词：
Algorithmic Analysis Algorithms Benchmarking Biodistribution Cell membrane Cells Cicatrix Clinic Clinical Clinical Management Clinical Treatment Color Contrast Media Data Detection Disease Dyes Environment Evaluation Excision Image In Vitro Inflammatory Light Lymph Node Dissections Lymphedema Malignant - descriptor Malignant Neoplasms Maps Measurement Metastatic Neoplasm to Lymph Nodes Methodology Methods Microelectrodes Molecular Mus Neoplasm Metastasis Nodal Noise Non-Invasive Cancer Detection Non-Malignant Patients Primary Neoplasm Property Reporter Research Resolution Risk Sensitivity and Specificity Sentinel Lymph Node Sentinel Lymph Node Biopsy Signal Transduction Staging Stimulus Technology Testing Time Tissues Work base draining lymph node extracellular imaging modality improved in vivo lymph nodes malignant breast neoplasm melanoma nano neoplastic cell nerve damage novel optoacoustic tomography patient stratification photoacoustic imaging ratiometric response sound spectroscopic imaging tissue phantom tumor wound

项目摘要

Malignant melanoma is one of the fastest rising cancers in the US. While treatment for clinical stage I and II melanoma involves wide local excision of the primary tumor, with staging of the regional lymph nodes by sentinel lymph node (SLN) biopsy, SLN biopsy is fraught with false-negative results. Technology that would reliably detect nodal metastases, not just the first draining node, could improve the sensitivity of melanoma nodal staging. Therefore, our objective is to (1) develop, characterize, validate and compare (A) optoacoustic ultra-acidic pH-responsive acidic pH targeted dye, pHO dye, and (B) external cell membrane anchored, V7- pHO, for tumor detection by multispectral optoacoustic tomography (MSOT) and (2) provide real-time color maps of tissue pH to allow for identification of regions of tumor in lymph nodes. Based on our preliminary data, we reason that it is possible to use our targeting methodology to identify very small metastases, which would allow complete lymph node dissection to be performed only for the 15% to 20% of patients who actually have cancer in the non-sentinel nodes. We hypothesize that pHO and V7-pHO dyes will facilitate detection of melanoma within lymph nodes and differentiate it from non-malignant, fibrous, or inflammatory tissue with high sensitivity and specificity using multispectral optoacoustic tomography. To test our hypothesis, we propose the following aims: 1) characterize and validate pHO and V7-pHO dyes to target acidic pHe for detection of tumor cells in vitro and in tissue phantoms; 2) assess pHO and V7-pHO dyes to facilitate detection of melanoma from non-malignant tissue in vivo using multispectral optoacoustic tomography; and 3) develop ratiometric algorithms based upon the spectral modulation of the pHO and V7-pHO dyes to produce real-time pHe measurement color maps and bi-color maps of tumors. Successful identification of melanoma containing lymph nodes using pHO or V7-pHO dyes detected using MSOT has potential to stratify patients for treatment in the clinic. Identification of metastases in lymph nodes or elsewhere in melanoma patients has potential for game- changing clinical management of patients with melanoma.

恶性黑色素瘤是美国发病率上升最快的癌症之一。同时治疗临床I期和II期