Clinical application of noninvasive and nonradioactive determination of microscopic lymph node tumor status by multispectral optoacoustic imaging

Objectives Sentinel lymph node (SLN) staging is included in various cancer guidelines to identify microscopic metastatic disease. This complex, time- and cost-intensive procedure includes radioactive tracing and could be avoided if noninvasive and nonradioactive imaging of nodal involvement was available. Here we present a noninvasive strategy with a high potential to reduce the number of invasive SLN procedures.

Methods ICG was used in melanoma patients to visualize the SLN via multispectral optoacoustic tomography (MSOT), which subsequentaly assessed its status. MSOT data was compared to standard 99mTc-nanocolloid-guided SLNE followed by conventional pathological analysis. Excised SLN scanned by MSOT were compared to standard histology.

Results With a sensitivity of 4 cells, MSOT increased the detection rate in 506 excised SLN of 214 melanoma patients. In 20 patients, MSOT identified tumor-free SLN in vivo with zero false negatives. MSOT was used to determine melanin signals from the SLN in direct comparison to standard 99mTc-nanocolloid-guided SLNE followed by conventional pathological analysis of the SLN. MSOT showed 15/41 (36.6%) SLNs in the in vivo clinical cohort contained no melanin.

Conclusions MSOT imaging of conventionally resected SLNs may allow a rapid, inexpensive, and sensitive detection of metastasis in SLN, which can also be used to guide histology. We could not only significantly increase the detection rate of tumor involvement ex vivo in excised SLN but could also determine in vivo tumor-free SLN in melanoma patients without false negatives. Therefore, we present a novel noninvasive strategy which enables protection for a significant number of melanoma patients from excessive, radioactive and needless surgery.

Research Support This work was supported by a grant (An-2012-0036) from the Mercator Research Center Ruhr and by a grant (Nr. 2013.113.1) from the Wilhelm Sander-Stiftung.