CT Imaging of Enzymatic Activity in Cancer Using Covalent Probes Reveal a Size-Dependent Pattern

Journal of the American Chemical Society
Darya TsvirkunGalia Blum

Abstract

X-ray CT instruments are among the most available, efficient, and cost-effective imaging modalities in hospitals. The field of CT molecular imaging is emerging which relies mainly on the detection of gold nanoparticles and iodine-containing compounds directed to tagging a variety of abundant biomolecules. Here for the first time we attempted to detect enzymatic activity, while the low sensitivity of CT scanners to contrast reagents made this a challenging task. Therefore, we developed a new class of nanosized cathepsin-targeted activity-based probes (ABPs) for functional CT imaging of cancer. ABPs are small molecules designed to covalently modify enzyme targets in an activity-dependent manner. Using a CT instrument, these novel probes enable detection of the elevated cathepsin activity within cancerous tissue, thus creating a direct link between biological processes and imaging signals. We present the generation and biochemical evaluation of a library of ABPs tagged with different sized gold nanoparticles (GNPs), with various ratios of cathepsin-targeting moiety and a combination of different polyethylene glycol (PEG) protective layers. The most potent and stable GNP-ABPs were applied for noninvasive cancer imaging in mice. Sur...Continue Reading

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Citations

Jul 3, 2019·Small·Dong LuoJames P Basilion
Apr 2, 2020·Expert Opinion on Therapeutic Targets·Matej VizovišekBoris Turk
Jul 22, 2020·Advanced Healthcare Materials·Xianfu MengWenbo Bu
Sep 3, 2020·Chemical Science·Dongdong SuXueyun Gao
May 21, 2019·Chemical Society Reviews·Xiaofeng ChenHuanghao Yang
Apr 4, 2021·International Journal of Molecular Sciences·Matej VizovisekSimone Schuerle
May 29, 2021·Radiology. Imaging Cancer·Christina H Liu, Piotr Grodzinski
Jun 8, 2021·Advanced Functional Materials·Mehdi AziziMichael R Hamblin
Jun 30, 2021·Journal of Nanobiotechnology·Jingqi XinFeifei An

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Methods Mentioned

BETA
X-ray
amidation
Dynamic
transmission electron microscopy
dynamic light scattering
thermal dissociation
flame atomic absorption spectroscopy

Software Mentioned

SPSS
Excel
GraphPad Prism
SkyScan CT - Volume ( “ CTVol

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