Washington University

Jothilingam Sivapackiam

Vijay K Sharma

David Piwnica-Worms

Sundaram S M Guruswami

G S M Sundaram

Provided herein are compounds for the imaging and treatment of TDP43-mediated disorders. The compounds disclosed bind TDP43 aggregates and may be used to diagnose and treat amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Organomedicinals for imaging and treatment of neurodegenerative disorders

Probes which target diffuse and fibrillar forms of amyloid beta (A&#x3b2;) are described. These probes demonstrate high initial brain penetration and facile clearance from non-targeted regions. The agents can be used to image amyloid quantitatively for monitoring efficacy of A&#x3b2;-modifying therapeutics and assist in premortem diagnosis of Alzheimer's disease (AD). Disclosed probes can bind A&#x3b2; aggregates of preformed A&#x3b2;fibrils in vitro and can be used to image fibrillar and diffuse plaques ex vivo in brain sections. Disclosed probes can be used to determine A&#x3b2; burden in early stages of AD. These probes can be used for multimodality imaging of A&#x3b2;. F-AI-187 (1 &#x3bc;M) can detect A&#x3b2; plaques in brain sections of APP/PS1 mice. F-AI-187 (10 &#x3bc;M) can detect A&#x3b2; plaques in the frontal lobe in a brain section of a patient with confirmed AD. Some probes can be used for fluorescence imaging of plaque.

Heterocyclic molecules for biomedical imaging and therapeutic applications

Tracers that can be used for PET or SPECT imaging of the distribution of Pgp are disclosed. The tracers are metalloprobes that can comprise a radioactive metal ion such asGa orGa. Methods of synthesizing the tracers, and methods of imaging heart and other tissues are also disclosed. The tracers can be used to obtain high signal-to-background ratios for imaging tissues in vivo such as heart or tumor tissue. In various embodiments, disclosed tracers can exhibit, a) enhanced first pass extraction into heart tissue compared to presently available probes, b) linearity with true blood flow, c) enhanced detection of myocardial viability compared to presently available probes, d) reduced liver retention compared to presently available probes, and e) more efficient clearance from non-cardiac and adjoining tissues compared to presently available probes.

Growing community of inventors

St. Louis, MO, United States of America

Jothilingam Sivapackiam