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Photodynamic and photoimmunotherapy are novel, experimental approaches in oncology, especially in the treatment of head, neck, skin, and ocular cancers. These approaches make use of a photosensitizer chemical, in the presence of molecular oxygen. Following exposure to a light source, the photosensitizer chemical converts molecular oxygen into singlet oxygen that induces cell death. IRDye 700DX dye’s photosensitizer properties, and the ability to covalently attach the dye to targeting molecules have rendered it a suitable fluorophore for both non-targeted (photodynamic) and targeted photoimmuno) applications.
Evaluating efficacy of photoimmuno-therapy in a mouse model of lung cancer. A targeted monoclonal antibody-photo-absorber conjugate (APC) comprising of IRDye 700DX dye was administered to mice. In vivo imaging was performed at specified time points with the Pearl Impulse imager. Mice receiving the combination of APC and NIR (NIR-PIT) showed tumor shrinkage compared to controls. Adapted from figures 3A-3D in Nagaya et al.
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Optoacoustic imaging, also known as photoacoustic imaging or multispectral optoacoustic tomography (MSOT) is an optical imaging modality that employs near-infrared light illumination for ultrasound detection. Near-infrared fluorophore IRDye 800CW and QC-1 (quencher) undergoes optoacoustic effect following exposure to an MSOT imager and allows ultrasound detection from tissue.
Evaluating renal function in mouse models using multispectral optoacoustic tomography (MSOT). Control and Adriamycin-treated mice (to induce nephropathy) were administered IRDye 800CW for evaluating dye clearance and kidney function by MSOT imaging. Adapted from figures 3A-3E in Scarfe et al.
Pre-clinical biodistribution labeling therapeutic agents and theranostics with near-infrared dyes like IRDye 800CW enables assessment of biological distribution, uptake, localization, and specificity of the targeting molecules. For FRET applications and in vivo biochemical studies, dual labeling of the targeting molecules with a fluorophore and a quencher (like QC-1) greatly assists in imaging.
Measuring biochemical activity of ATX (autotaxin) in tumor bearing mice in vivo. An AR-2 probe comprising of IRDye 800CW and QC-1 fluorophores was administered to tumor-bearing mice without (vehicle) and with ATX inhibitor (PF-8380). Upon cleavage by ATX, near-infrared fluorescence signal from probe components allowed in vivo biochemical characterization of ATX activity. Adapted from figures 6A–6C in Madan et al.
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Intraoperative visualization of small cancerous lesions. Mice injected intraperitoneally with cancer cells expressing the surface protein EpCAM, were administered IRDye-labeled EpCAM-specific antibody. Detection and imaging of cancer lesions was performed using the Pearl Imager. Adapted from figures 5a-5b in van Driel et al.
Targeting molecules conjugated to near-infrared dyes such as IRDye 800CW can aid surgeons by enhancing visualization during procedures. Fluorophores can also be used as imaging agents to improve contrast. Optical imaging can improve surgical outcomes in neurosurgery, angiography, lymph node mapping, and tumor resection.
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- Nagaya T, Nakamura Y, Sato K, et al. Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody. Oncotarget. 2017;8(5):8807-8817. doi:10.18632/oncotarget.12410.
- Scarfe L, Rak-Raszewska A, Geraci S, et al. Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy. Scientific Reports. 2015;5:13601. doi:10.1038/srep13601.
- Madan D, Ferguson CG, Lee WY, Prestwich GD, Testa CA. Non-Invasive Imaging of Tumors by Monitoring Autotaxin Activity Using an Enzyme-Activated Near-Infrared Fluorogenic Substrate. Bogyo M, ed. PLoS ONE. 2013;8(11):e79065. doi:10.1371/journal.pone.0079065.
- Van Driel PBAA, Boonstra MC, Prevoo HAJM, et al. EpCAM as multi-tumour target for near-infrared fluorescence guided surgery. BMC Cancer. 2016;16:884. doi:10.1186/s12885-016-2932-7.