The monitoring of vascular-targeted therapies using magnetic resonance imaging, computed tomography or ultrasound is limited by their insufficient spatial resolution. Here, by taking advantage of the intrinsic optical properties of haemoglobin, we show that raster-scanning optoacoustic mesoscopy (RSOM) provides high-resolution images of the tumour vasculature and of the surrounding tissue, and that the detection of a wide range of ultrasound bandwidths enables the distinction of vessels of differing size, providing detailed insights into the vascular responses to vascular-targeted therapy. Using RSOM to examine the responses to vascular-targeted photodynamic therapy in mice with subcutaneous xenografts, we observed a substantial and immediate occlusion of the tumour vessels followed by haemorrhage within the tissue and the eventual collapse of the entire vasculature. Using dual-wavelength RSOM, which distinguishes oxyhaemoglobin from deoxyhaemoglobin, we observed an increase in oxygenation of the entire tumour volume immediately after the application of the therapy, and a second wave of oxygen reperfusion approximately 24 h thereafter. We also show that RSOM enables the quantification of differences in neoangiogenesis that predict treatment efficacy.
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The authors declare that all data from this study are available within the Article and its Supplementary Information. Raw data for the individual measurements are available on reasonable request.
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We thank N. Fan of the MSKCC Molecular Cytology Core Facility for assistance with histology; Y. Romin for support and feedback on image analysis; and D. Yarilin of the MSKCC Molecular Cytology Core Facility for immunohistochemistry. This study was funded by the Thompson Family Foundation (Wade F. B. Thompson grant to J.C., A.S. and J.G.) and the National Cancer Institute (grant no. R01 CA212379 to J.G.). The study was also supported in part by the European grant INNODERM (no. 687866) Horizon 2020. We acknowledge P. Zanzonico and V. Ann Longo of the Small Animal Imaging Core Facility of MSKCC for their support (the Core is funded by the NIH Cancer Centre Support grant no. P30 CA008748).
V.N. is a shareholder in iThera Medical GmbH in Munich, Germany, which produces a commercial version of the monospectral RSOM (not used in this study). A.S. is an inventor of padeliporfin and has a financial interest from licensing fees.
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Haedicke, K., Agemy, L., Omar, M. et al. High-resolution optoacoustic imaging of tissue responses to vascular-targeted therapies. Nat Biomed Eng 4, 286–297 (2020). https://doi.org/10.1038/s41551-020-0527-8
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