Developing the 134 Ce and 134 La pair as companion positron emission tomography diagnostic isotopes for 225 Ac and 227 Th radiotherapeutics

Developing targeted α-therapies has the potential to transform how diseases are treated. In these interventions, targeting vectors are labelled with α-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 α-emitting isotopes such as 225 Ac and 227 Th are incompatible with PET imaging. Here we overcame this obstacle by developing large-scale (Ci-scale) production and purification methods for 134 Ce. Subsequent radiolabelling and in vivo PET imaging experiments in a small animal model demonstrated that 134 Ce (and its 134 La daughter) could be used as a PET imaging candidate for 225 Ac III (with reduced 134 Ce III ) or 227 Th IV (with oxidized 134 Ce IV ). Evaluating these data alongside X-ray absorption spectroscopy results demonstrated how success relied on rigorously controlling the Ce III /Ce IV redox couple.