Here we have validated a commercially available dye, CJ215 from ProImaging for enhanced cancer delineation. The dye (which does not require antibody or peptide conjugation) was found to be effective for both NIR and SWIR fluorescence imaging methods in preclinical breast, fibrosarcoma and prostate tumor models. The dye was effective for screening and resection and achieved some of the best-in-class tumor to organ ratios, e.g., tumor to muscle of 88.1, to liver of 17.9, to lungs of 12.9 and to kidney of 5 highlighting its renal clearance method. We briefly summarize the proposed mechanism of uptake and highlight the potential for clinical translation.
In this work we highlight the preclinical optimization of targeted tumor fluorophores for delineation. We utilize shortwave infrared fluorescence imaging (SWIRFI) under non-gated or filtered ambient lighting conditions to achieve a symbiotic fluorescence guided surgery ecosystem for unprecedented tumor contrast. With two commercially available targeted dyes we readily achieved tumor to muscle ratios in the ranges of 40 to 80, with exposure times as low as 1 ms within ANSI limited laser exposures. We highlight the metrics which can be used to quantify this contrast and signal, and further highlight the need for standardized metrics in academic and industry settings.
The advantages of shortwave infrared (SWIR, 900-1700 nm) imaging over NIR (650-900 nm) include reduced tissue optical aberrations, increased depth penetration along with improved resolution and contrast. Preclinical SWIR imaging has focused on system development and novel fluorophore development with a goal of targeted tumor resection for clinical translation. Clinical SWIR imaging has focused on indocyanine green (ICG) and the enhanced permeability and retention effect for resection with significant advantages. In this work we preclinically validate the pH low insertion peptide (pHLIP) conjugated to ICG (pHLIP ICG, currently in clinical trials) as a suitable cancer targeted fluorophore for cancer resection.
New technologies are needed for the identification of therapeutic vulnerabilities in cancers and neurodegenerative diseases. Autophagy is a cellular process with important functions that drive many such diseases. We developed a near-infrared optical nanosensor that measures autophagy-mediated changes in intralysosomal pH in cells and in vivo. The nanosensors, based on quantum defects on carbon nanotubes, are taken up by the lysosomes, where emission shifts in response to local pH. Using hyperspectral imaging, the sensors facilitated spatial, dynamic, and quantitative mapping of subtle changes in pH within tumor models. Monitoring the intratumorally-injected nanosensors enabled dynamic tracking of autophagy upon pharmacologic perturbation.
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