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性的肿瘤。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种最常见的癌症，给健康和经济带来了巨大的负担。黑色素瘤早期转移到区域淋巴结，需要前哨淋巴结(SLN)的组织学状态来预测和决定患者的生存。因此，在当前的2009年AJCC指南中，建议采用前哨淋巴结切除术(SLNE)。经过几十年的广泛应用，SLNE结合组织学分析已被证明是有效和可靠的，但它也有缺点。靶向摘除SLN的黄金标准是使用99m-氚(99mTc)的淋巴核素扫描，这总是对患者和(在较小程度上)照顾者来说是一种放射性负担。此外，在世界范围内，~(99m)Tm也存在短缺。SLNE进一步是一种成本非常高的干预措施，具有潜在的发病率，并未被发现可改善患者的总体生存。由于只对结节的一部分进行组织学采样，病理切片的最佳模式仍然存在争议，这在一定程度上可以解释已报道的SLNE的高假阴性率(9-44%)。这些缺点表明，应该探索SLN识别和诊断的替代策略。在拟议的拨款中，我们将开发一种新的成像方法，该方法具有以高灵敏度和特异度量化黑色素瘤引流淋巴结中无色素性和黑色素性癌细胞负荷的潜力。最终，我们将开发出第一种也是唯一一种具有成本效益的、非侵入性和非放射性的方法，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，在这些肿瘤中，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.