Imaging the heterogeneity of the tumor microenvironment is thought to be valuable for assessing the efficacy of a cancer therapy. However, due to the insufficient resolution of clinically available molecular imaging tools such as positron emission tomography, this feat is currently not achievable. Here, we demonstrate that revealing the TME is possible with immuno-near-infrared-fluorescence (Immuno-NIRF) imaging. Moreover, we combined immuno-NIRF with optical coherence tomography (OCT) to provide structural context to the molecular images. The combination of the two techniques may represent a novel tool in the operating room for assessing development or early diagnosis of tumors.
Determining cancer phenotypes early in the development of the disease is fundamental to increase the efficacy of therapy. To this end, genetic profiling of bioptic tissue has become an indispensable tool; however, erroneous sampling of the tissue leads to a considerable number of false negatives. To address this shortcoming, we developed a motorized endoscope (outer diameter 1.35mm) combining near-infrared fluorescence (NIRF) imaging and optical coherence tomography (OCT) at a frame rate of 52 images per second. Here, NIRF imaging is used to guide biopsies by targeting the tumor with fluorescently labeled monoclonal antibodies that attach to receptors on the membrane of cancer cells. Furthermore, the biopsy forceps severely alter the structure of the tissue and OCT can help in reconstructing the morphology thanks to its 10 µm resolution.
We demonstrated the device on a mouse model bearing human colon cancer, by administering a sub-therapeutic dose of a monoclonal antibody labeled with both a PET tracer and a near infrared molecule that is already used in several clinical trials (89Zr-Labetuzumab-IRdye800CW). In addition to successfully imaging 1 mm tumors with our endoscope, we developed a NIRF-OCT handheld scanner that allows mapping of the distribution of the antibody with high resolution. Finally, we also performed PET in order to quantify the bio-distribution of the drug in the mouse.
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