Cancer cells extract oxygen and nutrients from surrounding blood vessels to fuel their rapid and uncontrolled growth. A method that is capable of quantitatively assessing the oxyhemoglobin saturation (sO2) status of tumor blood vessels in vivo could provide insights into such metabolic activities; however, this remains a challenge.
In a study published in Nature Nanotechnology, research teams led by Prof. ZHONG Yeteng, Prof. CHEN Chunying, and Prof. HU Zhiyuan at National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences, developed an in vivo dynamic sO2 imaging technique for the precise measurement and real-time monitoring of the sO2 levels in complex mouse tumor blood vessels, based on fluorescence imaging in the near-infrared IIb (NIR-IIb; 1500–1700 nm) window.
The researchers used rare-earth (RE) nanoparticles, whose 1550 nm luminescence is ideal for deep-tissue in vivo imaging due to suppressed photon scattering and completely eliminated autofluorescence. Upon excitation at two specific wavelengths, 650 nm and 980 nm, the sO2 levels in blood can be quantified from the NIR-IIb signals of intravenously injected RE nanoprobe.
Capitalizing on this sO2 imaging technique, a significant difference in blood sO2 levels was found between different mouse tumor models, which could reflect their heterogeneous metabolic activities. The researchers also found that a favorable response to cancer immunotherapy could result in a dramatic decrease in the sO2 level of tumor blood vessels, which could facilitate a more accurate prediction of immunotherapy outcomes.
The researchers further developed a two-plex NIR-IIb fluorescence imaging technique by utilizing another type of RE nanoprobe, allowing for the simultaneous acquisition of in vivo sO2 imaging and programmed death-ligand 1 (PD-L1) molecular imaging.
“At first, we designed a two-plex NIR-IIb imaging strategy: one RE nanoprobe was used to perform sO2 imaging, and another RE nanoprobe could be used for targeted molecular imaging, without interference between the channels. We chose to perform PD-L1 molecular imaging by using RE nanoprobe conjugated with anti-PD-L1 antibody, as this approach has been well-described in previous papers.” said FANG Zhiguo, first co-author of the paper. “We found an interesting result in CT26 tumors, which highly express PD-L1. After the anti-PD-L1 antibody treatment, the sO2 levels of the tumor vessels decreased, which could be deemed a positive response to the immunotherapy.”
“Knowledge of such specific sO2 levels in tumor blood vessels could offer new insights into the metabolic profiles of individual malignant cells and tumors. This new imaging modality holds promise for further investigations into the heterogeneous metabolic microenvironment of tumors.” said Prof. ZHONG.
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