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. 2021 Mar;13(3):284-289.
doi: 10.1038/s41557-020-00598-7. Epub 2020 Dec 14.

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

Tyler A Bailey #  1   2 , Veronika Mocko #  3 , Katherine M Shield #  1   2 , Dahlia D An  2 , Andrew C Akin  3 , Eva R Birnbaum  3 , Mark Brugh  3 , Jason C Cooley  3 , Jonathan W Engle  4 , Michael E Fassbender  3 , Stacey S Gauny  2 , Andrew L Lakes  2 , Francois M Nortier  3 , Ellen M O'Brien  3 , Sara L Thiemann  3 , Frankie D White  3 , Christiaan Vermeulen  5 , Stosh A Kozimor  6 , Rebecca J Abergel  7   8
Affiliations

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

Tyler A Bailey et al. Nat Chem. 2021 Mar.

Abstract

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 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 225AcIII (with reduced 134CeIII) or 227ThIV (with oxidized 134CeIV). Evaluating these data alongside X-ray absorption spectroscopy results demonstrated how success relied on rigorously controlling the CeIII/CeIV redox couple.

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