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

Tyler A. Bailey; Veronika Mocko; Katherine M. Shield; Dahlia D. An; Andrew C. Akin; Eva R. Birnbaum; Mark Brugh; Jason C. Cooley; Jonathan W. Engle; Michael E. Fassbender; Stacey S. Gauny; Andrew L. Lakes; Francois M. Nortier; Ellen M. O’Brien; Sara L. Thiemann; Frankie D. White; Christiaan Vermeulen; Stosh A. Kozimor; Rebecca J. Abergel

doi:10.1038/s41557-020-00598-7

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

Tyler A. Bailey, Veronika Mocko, Katherine M. Shield, Dahlia D. An, Andrew C. Akin, Eva R. Birnbaum, Mark Brugh, Jason C. Cooley, Jonathan W. Engle, Michael E. Fassbender, Stacey S. Gauny, Andrew L. Lakes, Francois M. Nortier, Ellen M. O’Brien, Sara L. Thiemann, Frankie D. White, Christiaan Vermeulen, Stosh A. Kozimor, Rebecca J. Abergel

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 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. [Figure not available: see fulltext.]

Original language	English
Pages (from-to)	284-289
Number of pages	6
Journal	Nature Chemistry
Volume	13
Issue number	3
DOIs	https://doi.org/10.1038/s41557-020-00598-7
State	Published - Mar 2021
Externally published	Yes

Funding

We thank M. Janabi for help with the μ-PET instrument and G.J.-P. Deblonde for discussions. This research was supported by the US Department of Energy (DOE) Isotope Program, managed by the Office of Science for Nuclear Physics (LBNL contract DE-AC02-05CH11231; LANL Contract 89233218CNA000001). LANL is an affirmative action/equal opportunity employer managed by Triad National Security, LLC, for the National Nuclear Security Administration of the US DOE. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, was supported by the DOE, Office of Science, Office of Basic Energy Sciences under contract no. DE-AC02-76SF00515. We acknowledge additional support from a DOE Integrated University Program graduate research fellowship (K.M.S.) and a Nuclear Regulatory Commission Faculty Development Grant (NRC-HQ-84-14-G-0052; R.J.A.). Dedication: We dedicate this work to the memory of our colleague and friend Dr. J. P. O’Neil.

Funders	Funder number
DOE Integrated University
Office of Basic Energy Sciences	DE-AC02-76SF00515
Office of Science for Nuclear Physics
US Department of Energy
U.S. Department of Energy
U.S. Nuclear Regulatory Commission	NRC-HQ-84-14-G-0052
Office of Science
Lawrence Berkeley National Laboratory	DE-AC02-05CH11231
Los Alamos National Laboratory	89233218CNA000001

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Bailey, T. A., Mocko, V., Shield, K. M., An, D. D., Akin, A. C., Birnbaum, E. R., Brugh, M., Cooley, J. C., Engle, J. W., Fassbender, M. E., Gauny, S. S., Lakes, A. L., Nortier, F. M., O’Brien, E. M., Thiemann, S. L., White, F. D., Vermeulen, C., Kozimor, S. A., & Abergel, R. J. (2021). Developing the ¹³⁴Ce and ¹³⁴La pair as companion positron emission tomography diagnostic isotopes for ²²⁵Ac and ²²⁷Th radiotherapeutics. Nature Chemistry, 13(3), 284-289. https://doi.org/10.1038/s41557-020-00598-7

@article{c179968da6c049b9b45654122d8f934f,

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

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. [Figure not available: see fulltext.]",

author = "Bailey, {Tyler A.} and Veronika Mocko and Shield, {Katherine M.} and An, {Dahlia D.} and Akin, {Andrew C.} and Birnbaum, {Eva R.} and Mark Brugh and Cooley, {Jason C.} and Engle, {Jonathan W.} and Fassbender, {Michael E.} and Gauny, {Stacey S.} and Lakes, {Andrew L.} and Nortier, {Francois M.} and O{\textquoteright}Brien, {Ellen M.} and Thiemann, {Sara L.} and White, {Frankie D.} and Christiaan Vermeulen and Kozimor, {Stosh A.} and Abergel, {Rebecca J.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = mar,

doi = "10.1038/s41557-020-00598-7",

language = "English",

volume = "13",

pages = "284--289",

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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 2021, 'Developing the ¹³⁴Ce and ¹³⁴La pair as companion positron emission tomography diagnostic isotopes for ²²⁵Ac and ²²⁷Th radiotherapeutics', Nature Chemistry, vol. 13, no. 3, pp. 284-289. https://doi.org/10.1038/s41557-020-00598-7

TY - JOUR

T1 - Developing the 134Ce and 134La pair as companion positron emission tomography diagnostic isotopes for 225Ac and 227Th radiotherapeutics

AU - Bailey, Tyler A.

AU - Mocko, Veronika

AU - Shield, Katherine M.

AU - An, Dahlia D.

AU - Akin, Andrew C.

AU - Birnbaum, Eva R.

AU - Brugh, Mark

AU - Cooley, Jason C.

AU - Engle, Jonathan W.

AU - Fassbender, Michael E.

AU - Gauny, Stacey S.

AU - Lakes, Andrew L.

AU - Nortier, Francois M.

AU - O’Brien, Ellen M.

AU - Thiemann, Sara L.

AU - White, Frankie D.

AU - Vermeulen, Christiaan

AU - Kozimor, Stosh A.

AU - Abergel, Rebecca J.

PY - 2021/3

Y1 - 2021/3

N2 - 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. [Figure not available: see fulltext.]

AB - 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. [Figure not available: see fulltext.]

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ER -

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

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