Abstract
Tumor angiogenesis is enhanced in all types of tumors to supply oxygen and nutrients for their growth and metastasis. With the development of anti-angiogenic drugs, the importance of technology that closely monitors tumor angiogenesis has also been emerging. However, to date, the technology for observing blood vessels requires specialized skills with expensive equipment, thereby limiting its applicability only to the laboratory setting. Here, we used a preclinical optical imaging system for small animals and, for the first time, observed, in real time, the entire process of blood vessel development in tumor-bearing mice injected with indocyanine green. Time-lapse sequential imaging revealed blood vessel volume and blood flow dynamics on a microscopic scale. Upon analyzing fluorescence dynamics at each stage of tumor progression, vessel volume and blood flow were found to increase as the tumor developed. Conversely, these vascular parameters decreased when the mice were treated with angiogenesis inhibitors, which suggests that the effects of drugs targeting angiogenesis can be rapidly and easily screened. The results of this study may help evaluate the efficacy of angiogenesis-targeting drugs by facilitating the observation of tumor blood vessels easily in a laboratory unit without large and complex equipment.
Highlights
Angiogenesis progresses in solid tumors to provide the oxygen and nutrients necessary for the continuous growth of the tissue and metastasis [1]
We further confirmed that the blood vessels within the tumor or tumor periphery regions clearly visible with the naked eye in the photographs were the same as those seen in Imax and FluAngio obtained from indocyanine green (ICG) imaging (Figure S3)
We developed a novel imaging system to observe the entire process of tumor angiogenesis and to analyze the vascular dynamics in real time
Summary
Angiogenesis progresses in solid tumors to provide the oxygen and nutrients necessary for the continuous growth of the tissue and metastasis [1]. Research on drugs targeting angiogenesis as an effective strategy for cancer treatment is ongoing. In response to angiogenesis inhibitors, vascular elements such as vessel volume, blood flow, and microvascular density change simultaneously and dynamically, and these changes occur over several days [4]. Their local changes have the potential to be biomarkers in cancer treatment, and a method to measure them longitudinally is essential for judging therapeutic effects. To screen drugs against angiogenesis and to predict their therapeutic effects, it is important to develop a practical tool that can repeatedly observe and measure vascular changes in tumors
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