Preclinical evaluation of a novel cathepsin-activated fluorescent probe VGT-309 for identification of ovarian cancer in a mouse model (248)

Santiago, Nicole Lugo; Wen, Wei; Kohut, Andrew; Bensen, Eric S.; Santini, John T.; Yim, John H.; Fong, Yuman; Han, Ernest

doi:10.1016/s0090-8258(22)01471-8

Cited by 2 publications

(2 citation statements)

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“…Given the ubiquitous role for cathepsins in cancer progression, there is a high likelihood that VGT-309 can be effectively applied in other cancer types. The probe is currently in preclinical development for breast, esophogeal, ovarian, gastric, and colon cancers. − LUM015 is another cathepsin-activatable probe, a Cy5-QSY21-flanked SBP, that has gone through phase II trials to detect residual breast cancer during surgery; additional trials are currently recruiting for other cancer types. − …”

Section: Cysteine Protease Probesmentioning

confidence: 99%

Chemical Tools to Image the Activity of PAR-Cleaving Proteases

Lee,

Tantisirivat,

Edgington-Mitchell

2023

ACS Bio Med Chem Au

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Protease-activated receptors (PARs) comprise a family of four G protein-coupled receptors (GPCRs) that have broad functions in health and disease. Unlike most GPCRs, PARs are uniquely activated by proteolytic cleavage of their extracellular N termini. To fully understand PAR activation and function in vivo, it is critical to also study the proteases that activate them. As proteases are heavily regulated at the post-translational level, measures of total protease abundance have limited utility. Measures of protease activity are instead required to inform their function. This review will introduce several classes of chemical probes that have been developed to measure the activation of PAR-cleaving proteases. Their strengths, weaknesses, and applications will be discussed, especially as applied to image protease activity at the whole organism, tissue, and cellular level.

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Section: Cysteine Protease Probesmentioning

confidence: 99%

Chemical Tools to Image the Activity of PAR-Cleaving Proteases

Lee,

Tantisirivat,

Edgington-Mitchell

2023

ACS Bio Med Chem Au

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“…This results in rapid generation of signal contrast with low overall backgrounds. In particular, several protease-activated fluorescent imaging probes have reached clinical studies. − Examples include probes that are activated by matrix metallo proteases secreted by tumor cells as well as lysosomal cathepsin proteases secreted by tumor associated macrophages (TAMs) . For many protease-activated imaging agents, a peptidic substrate scaffold links a dye-quencher pair in close proximity (<10 nm) enabling Förster resonance energy transfer (FRET) to occur.…”

Section: Introductionmentioning

confidence: 99%

Protease Activated Probes for Real-Time Ratiometric Imaging of Solid Tumors

et al. 2023

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Surgery is the preferred treatment option for most solid tumors. However, inaccurate detection of cancer borders leads to either incomplete removal of malignant cells or excess excision of healthy tissue. While fluorescent contrast agents and imaging systems improve tumor visualization, they can suffer from low signal-to-background and are prone to technical artifacts. Ratiometric imaging has the potential to eliminate many of these issues such as uneven probe distribution, tissue autofluorescence, and changes in positioning of the light source. Here, we describe a strategy to convert quenched fluorescent probes into ratiometric contrast agents. Conversion of the cathepsin-activated probe, 6QC-Cy5, into a two-fluorophore probe, 6QC-RATIO, significantly improved signal-to-background in vitro and in a mouse subcutaneous breast tumor model. Tumor detection sensitivity was further enhanced using a dual-substrate AND-gate ratiometric probe, Death-Cat-RATIO, that fluoresces only after orthogonal processing by multiple tumor-specific proteases. We also designed and built a modular camera system that was coupled to the FDA-approved da Vinci Xi robot, to enable real-time imaging of ratiometric signals at video frame rates compatible with surgical workflows. Our results demonstrate that ratiometric camera systems and imaging probes have the potential to be clinically implemented to improve surgical resection of many types of cancer.

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Preclinical evaluation of a novel cathepsin-activated fluorescent probe VGT-309 for identification of ovarian cancer in a mouse model (248)

Cited by 2 publications

References 0 publications

Chemical Tools to Image the Activity of PAR-Cleaving Proteases

Chemical Tools to Image the Activity of PAR-Cleaving Proteases

Protease Activated Probes for Real-Time Ratiometric Imaging of Solid Tumors

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