Sentinel lymph node tumor burden quantified non-invasively and non-radioactively with multi-tracer and multispectral optoacoustic imaging

黑色素瘤皮肤癌是一种侵袭性和致命的肿瘤。根据世界卫生组织的数据，黑色素瘤的发病率增长速度比世界上任何其他主要癌症都要快。黑色素瘤是德国第五大常见癌症，造成了巨大的健康和经济负担。黑色素瘤早期转移到局部淋巴结，需要前哨淋巴结（SLN）的组织学状态来预测和确定患者的生存。因此，2009年AJCC指南推荐前哨淋巴结切除术（SLNE）。经过几十年的广泛应用，SLNE与组织学分析已被证明是有效和可靠的，但它确实有缺点。靶向清除SLN的金标准是使用99m-锝（99mTc）的淋巴显影术，它总是对患者和（在较小程度上）护理人员造成放射性负担。此外，全世界都在短缺锝-99m。此外，SLNE是一种成本非常高的干预措施，有潜在的发病率，没有发现能提高患者的总体生存率。由于仅对部分淋巴结进行组织学采样，因此病理切片的最佳模式仍存在争议，这可能部分解释了SLNE报告的高假阴性率（9-44%）。这些缺点表明，应该探索其他的SLN识别和诊断策略。在拟议的拨款中，我们将开发一种新的成像方法，该方法有可能以高灵敏度和特异性量化黑色素瘤引流淋巴结中的无色素瘤和黑色素瘤癌细胞负荷。最终，我们将开发出第一种也是唯一一种具有成本效益、无创和无放射性的方法，用于检测肿瘤引流淋巴结中癌细胞的微观水平。在未来，这种方法也可以应用于其他实体肿瘤，如乳腺癌，其经济和医疗影响将大得多。

Melanoma skin cancer is an aggressive and deadly tumor. According to the World Health Organization, the incidence of melanoma is increasing faster than any other major cancer in the world. Melanoma is the fifth most common cancer in Germany, posing a substantial health and economic burden. Melanoma metastasizes early into regional lymph nodes, requiring sentinel lymph node (SLN) histological status for prognostication and determination of patient survival. Sentinel lymph node excision (SLNE) is therefore recommended in the current 2009 AJCC guidelines. Widely used for decades, SLNE with histological analysis has proved to be effective and reliable, but it does have drawbacks. The gold standard for targeted extirpation of the SLN is lymphoscintigraphy using 99m-technetium (99mTc), which invariably represents a radioactive burden for patients and (to a lesser degree) caregivers. Furthermore there is a worldwide shortage of technetium-99m. SLNE is further a very cost-intensive intervention with potential morbidity, not found to improve overall patient survival. As only a portion of the node is sampled for histology, the optimal mode of pathological sectioning remains controversial and could in part explain the high false-negative rate of SLNE reported (9-44%). These drawbacks suggest that alternative strategies for SLN identification and diagnosis should be explored.In the proposed grant we will develop a new imaging approach which has the potential to quantify amelanotic and melanotic cancer cell burden in melanoma draining lymph nodes with high sensitivity and specificity. In the end we will have developed the first and only cost effective, noninvasive and nonradioactive approach for detecting microscopic levels of cancer cells in tumor draining lymph nodes. In the future this approach could also be applied to other solid tumors such as breast cancer where the economic and medical impact would be far greater.