Oxyhaemoglobin saturation NIR-IIb imaging for assessing cancer metabolism and predicting the response to immunotherapy.

In vivo quantitative assessment of oxyhaemoglobin saturation (sO 2 ) status in tumour-associated vessels could provide insights into cancer metabolism and behaviour. Here we develop a non-invasive in vivo sO 2 imaging technique to visualize the sO 2 levels of healthy and tumour tissue based on photoluminescence bioimaging in the near-infrared IIb (NIR-IIb; 1,500-1,700 nm) window. Real-time dynamic sO 2 imaging with a high frame rate (33 Hz) reveals the cerebral arteries and veins through intact mouse scalp/skull, and this imaging is consistent with the haemodynamic analysis results. Utilizing our non-invasive sO 2 imaging, the tumour-associated-vessel sO 2 levels of various cancer models are evaluated. A positive correlation between the tumour-associated-vessel sO 2 levels and the basal oxygen consumption rate of corresponding cancer cells at the early stages of tumorigenesis suggests that cancer cells modulate the tumour metabolic microenvironment. We also find that a positive therapeutic response to the checkpoint blockade cancer immunotherapy could lead to a dramatic decrease of the tumour-associated-vessel sO 2 levels. Two-plex dynamic NIR-IIb imaging can be used to simultaneously observe tumour-vessel sO 2 and PD-L1, allowing a more accurate prediction of immunotherapy response.