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

恶性黑色素瘤是美国增长最快的癌症之一。临床I期和II期的治疗 黑色素瘤涉及原发肿瘤的广泛局部切除，通过以下方法对区域淋巴结进行分期： 前哨淋巴结（SLN）活检，SLN活检充满了假阴性结果。技术， 可靠地检测淋巴结转移，而不仅仅是第一个引流淋巴结，可以提高黑色素瘤的敏感性 淋巴结分期。因此，我们的目标是（1）开发，表征，验证和比较（A）光声 超酸性pH响应性酸性pH靶向染料，pHO染料，和（B）外部细胞膜锚定的，V7- pHO，用于通过多光谱光声断层扫描（MSOT）进行肿瘤检测，以及（2）提供实时彩色 组织pH图，以识别淋巴结中的肿瘤区域。根据我们的初步数据， 我们的理由是，有可能使用我们的靶向方法来识别非常小的转移， 允许仅对15%至20%的实际存在淋巴结转移的患者进行完全淋巴结清扫。 非前哨淋巴结的癌症。我们假设pHO和V7-pHO染料将有助于检测 淋巴结内的黑色素瘤，并将其与非恶性，纤维或炎症组织区分开来， 灵敏度和特异性。为了验证我们的假设，我们提出了 以下目的：1）表征和验证pHO和V7-pHO染料以靶向酸性pHe用于检测肿瘤 2）评估pHO和V7-pHO染料，以促进检测来自 使用多光谱光声断层扫描在体内的非恶性组织;以及3）开发比率测量 基于pHO和V7-pHO染料的光谱调制的算法，以产生实时pHe 肿瘤的测量彩色图和双色图。成功识别含有淋巴的黑色素瘤 使用MSOT检测的使用pHO或V7-pHO染料的淋巴结有可能对患者进行分层，以进行治疗。 诊所在黑色素瘤患者中识别淋巴结或其他部位的转移具有潜在的博弈- 改变黑色素瘤患者的临床管理。

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.