4 research outputs found
Optimized Near-IR Fluorescent Agents for in Vivo Imaging of Btk Expression
Bruton’s
tyrosine kinase (Btk) is intricately involved in
anti-apoptotic signaling pathways in cancer and in regulating innate
immune response. A number of Btk inhibitors are in development for
use in treating B-cell malignancies and certain immunologic diseases.
To develop robust companion imaging diagnostics for in vivo use, we
set out to explore the effects of red wavelength fluorochrome modifications
of two highly potent irreversible Btk inhibitors, Ibrutinib and AVL-292.
Surprisingly, we found that subtle chemical differences in the fluorochrome
had considerable effects on target localization. Based on iterative
designs, we developed a single optimized version with superb in vivo
imaging characteristics enabling single cell Btk imaging in vivo.
This agent (Ibrutinib-SiR-COOH) is expected to be a valuable chemical
tool in deciphering Btk biology in cancer and host cells in vivo
Design, Synthesis, and Evaluation of a Low-Molecular-Weight <sup>11</sup>C‑Labeled Tetrazine for Pretargeted PET Imaging Applying Bioorthogonal in Vivo Click Chemistry
A low-molecular-weight
tetrazine labeled with the short-lived positron
emitter carbon-11 was developed as a bioorthogonal PET probe for pretargeted
imaging. A method for efficient and fast synthesis of this imaging
agent is presented using radiolabeling of a readily available precursor.
High reactivity with <i>trans</i>-cyclooctenes was observed
and in vivo investigations including PET/MR scanning showed homogeneous
biodistribution, good metabolic stability, and rapid excretion in
naive mice. These properties are key to the success of bioorthogonal <sup>11</sup>C-PET imaging, which has been shown in a simple pretargeting
experiment using TCO-modified mesoporous silica nanoparticles. Overall,
this <sup>11</sup>C-labeled tetrazine represents a highly versatile
and advantageous chemical tool for bioorthogonal PET imaging and enables
pretargeting approaches using carbon-11 for the first time
Isolation and Structure Elucidation of Pentahydroxyscirpene, a Trichothecene <i>Fusarium</i> Mycotoxin
Pentahydroxyscirpene, a novel trichothecene-type
compound, was
isolated from <i>Fusarium</i>-inoculated rice. The structure
of pentahydroxyscirpene was elucidated by 1D and 2D NMR spectroscopy
and X-ray single-crystal diffraction. The conformation in solution
was determined by NOESY experiments supported by quantum chemical
calculations. <i>In vitro</i> toxicity tests showed that
pentahydroxyscirpene inhibits protein synthesis as do other trichothecenes
Isolation and Structure Elucidation of Pentahydroxyscirpene, a Trichothecene <i>Fusarium</i> Mycotoxin
Pentahydroxyscirpene, a novel trichothecene-type
compound, was
isolated from <i>Fusarium</i>-inoculated rice. The structure
of pentahydroxyscirpene was elucidated by 1D and 2D NMR spectroscopy
and X-ray single-crystal diffraction. The conformation in solution
was determined by NOESY experiments supported by quantum chemical
calculations. <i>In vitro</i> toxicity tests showed that
pentahydroxyscirpene inhibits protein synthesis as do other trichothecenes