Deep tissue imaging of B16 melanoma in mice by Multispectral Optoacoustic Tomography

Abstract

Melanoma is an aggressive type of skin cancer that can metastasize to draining lymph nodes and distant organs. Early detection of melanoma holds the promise of improved patient outcomes by enabling earlier surgical intervention. Photoacoustic imaging of melanoma can be used to detect chemical entities that can absorb light of distinct wavelengths, such as dark-pigmented melanin produced by melanoma cells. Multi-Spectral Optoacoustic Tomographic (MSOT) imaging is whole-body photoacoustic imaging used to gain structural and functional information in mice or other animals. Here, we compared two routes of administration of the melanoma cells to determine the detectability of melanoma by MSOT either directly in the skin or deeper within mice. MSOT imaging was done at 5-day intervals to monitor melanoma growth and metastasis. MSOT signal for melanin was readily detectable in both models, but we did not observe metastasis from the skin in our intradermal model. Pseudo-metastasis was observed following intravenous administration with tumors primarily observed in lung, liver, and adrenal glands. We used standard histological analysis to characterize the melanoma tumors, and the extent of immune infiltrates. To further characterize the tumor microenvironment, we administer a molecular probe directed at neutrophil elastase and observed by four-channel MSOT signal unmixing neutrophil activity in intradermal tumors and surrounding tissues. Our results suggest that the rapid development of melanoma tumors (<21 days) may lead to the accumulation of neutrophils in the tumor areas. Further studies will determine the impact of these tumor-associated neutrophils and their role in preventing metastatic spread in mice with fully competent immune systems.