7 research outputs found
Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications
Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than [GdDOTA]−. These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy
Multisite Thrombus Imaging and Fibrin Content Estimation With a Single Whole-Body PET Scan in Rats
Collagen targeted MRI accurately measures the desmoplastic response to folfirinox treatment in a murine model of pancreatic cancer
Tailored Chemical Reactivity Probes for Systemic Imaging of Aldehydes in Fibroproliferative Diseases
During
fibroproliferation, protein-associated extracellular aldehydes
are formed by the oxidation of lysine residues on extracellular matrix
proteins to form the aldehyde allysine. Here we report three Mn(II)-based,
small-molecule magnetic resonance probes that contain α-effect
nucleophiles to target allysine in vivo and report on tissue fibrogenesis.
We used a rational design approach to develop turn-on probes with
a 4-fold increase in relaxivity upon targeting. The effects of aldehyde
condensation rate and hydrolysis kinetics on the performance of the
probes to detect tissue fibrogenesis non-invasively in mouse models
were evaluated by a systemic aldehyde tracking approach. We showed
that, for highly reversible ligations, off-rate was a stronger predictor
of in vivo efficiency, enabling histologically validated, three-dimensional
characterization of pulmonary fibrogenesis throughout the entire lung.
The exclusive renal elimination of these probes allowed for rapid
imaging of liver fibrosis. Reducing the hydrolysis rate by forming
an oxime bond with allysine enabled delayed phase imaging of kidney
fibrogenesis. The imaging efficacy of these probes, coupled with their
rapid and complete elimination from the body, makes them strong candidates
for clinical translation
Tailored Chemical Reactivity Probes for Systemic Imaging of Aldehydes in Fibroproliferative Diseases
During
fibroproliferation, protein-associated extracellular aldehydes
are formed by the oxidation of lysine residues on extracellular matrix
proteins to form the aldehyde allysine. Here we report three Mn(II)-based,
small-molecule magnetic resonance probes that contain α-effect
nucleophiles to target allysine in vivo and report on tissue fibrogenesis.
We used a rational design approach to develop turn-on probes with
a 4-fold increase in relaxivity upon targeting. The effects of aldehyde
condensation rate and hydrolysis kinetics on the performance of the
probes to detect tissue fibrogenesis non-invasively in mouse models
were evaluated by a systemic aldehyde tracking approach. We showed
that, for highly reversible ligations, off-rate was a stronger predictor
of in vivo efficiency, enabling histologically validated, three-dimensional
characterization of pulmonary fibrogenesis throughout the entire lung.
The exclusive renal elimination of these probes allowed for rapid
imaging of liver fibrosis. Reducing the hydrolysis rate by forming
an oxime bond with allysine enabled delayed phase imaging of kidney
fibrogenesis. The imaging efficacy of these probes, coupled with their
rapid and complete elimination from the body, makes them strong candidates
for clinical translation