Developing The Ce-134 And La-134 Pair As Companion Positron Emission Tomography Diagnostic Isotopes For Ac-225 And Th-227 Radiotherapeutics

Developing targeted alpha-therapies has the potential to transform how diseases are treated. In these interventions, targeting vectors are labelled with alpha-emitting radioisotopes that deliver destructive radiation discretely to diseased cells while simultaneously sparing the surrounding healthy tissue. Widespread implementation requires advances in non-invasive imaging technologies that rapidly assay therapeutics. Towards this end, positron emission tomography (PET) imaging has emerged as one of the most informative diagnostic techniques. Unfortunately, many promising alpha-emitting isotopes such as Ac-225 and Th-227 are incompatible with PET imaging. Here we overcame this obstacle by developing large-scale (Ci-scale) production and purification methods for Ce-134. Subsequent radiolabelling and in vivo PET imaging experiments in a small animal model demonstrated that Ce-134 (and its La-134 daughter) could be used as a PET imaging candidate for Ac-225(III) (with reduced Ce-134(III)) or Th-227(IV) (with oxidized Ce-134(IV)). Evaluating these data alongside X-ray absorption spectroscopy results demonstrated how success relied on rigorously controlling the Ce-III/Ce-IV redox couple.