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

Authors :
Bailey TA
Mocko V
Shield KM
An DD
Akin AC
Birnbaum ER
Brugh M
Cooley JC
Engle JW
Fassbender ME
Gauny SS
Lakes AL
Nortier FM
O'Brien EM
Thiemann SL
White FD
Vermeulen C
Kozimor SA
Abergel RJ
Source :
Nature chemistry [Nat Chem] 2021 Mar; Vol. 13 (3), pp. 284-289. Date of Electronic Publication: 2020 Dec 14.
Publication Year :
2021

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 <superscript>225</superscript> Ac and <superscript>227</superscript> Th are incompatible with PET imaging. Here we overcame this obstacle by developing large-scale (Ci-scale) production and purification methods for <superscript>134</superscript> Ce. Subsequent radiolabelling and in vivo PET imaging experiments in a small animal model demonstrated that <superscript>134</superscript> Ce (and its <superscript>134</superscript> La daughter) could be used as a PET imaging candidate for <superscript>225</superscript> Ac <superscript>III</superscript> (with reduced <superscript>134</superscript> Ce <superscript>III</superscript> ) or <superscript>227</superscript> Th <superscript>IV</superscript> (with oxidized <superscript>134</superscript> Ce <superscript>IV</superscript> ). Evaluating these data alongside X-ray absorption spectroscopy results demonstrated how success relied on rigorously controlling the Ce <superscript>III</superscript> /Ce <superscript>IV</superscript> redox couple.

Details

Language :
English
ISSN :
1755-4349
Volume :
13
Issue :
3
Database :
MEDLINE
Journal :
Nature chemistry
Publication Type :
Academic Journal
Accession number :
33318671
Full Text :
https://doi.org/10.1038/s41557-020-00598-7