Ce-134 and La-134 pair as companion PET diagnostic isotopes for Ac-225 and Th-227

Abstract

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