Imaging manganese trafficking in a neurodegenerative disorder of manganese overload

Metal Homeostasis in Cancer Radioresistance

Patients with loss of function mutations in the manganese efflux transporter SLC30A10 have systemic manganese overload, polycytheamia and Parkinsonian-like dystonia. We are using ⁵²Mn-PET and MRI to map manganese overload in an SLC30A10 KO mouse model.

There is an emerging role of manganese in cancer radioresistance as a regulator of oxidative stress mechanisms. We propose that molecular imaging techniques such as PET and MRI have the potential to predict radioresistance by non-invasively measuring manganese levels.

Genetic silencing of SLC39A8 to treat manganese overload

A brain penetrating ⁶⁴Cu complex for imaging copper overload in Wilson’s disease

We are proposing a novel class of therapies, antisense oligonucleotides, to alleviate neurological symptoms by silencing the manganese influx transporter SLC39A8.

Approaches are needed to assess cerebral copper overload and the effect of chelation therapy has on copper efflux. [⁶⁴Cu]Cu-GTSM will permit these investigations.