High yield cyclotron production of a novel 133/135La theranostic pair for nuclear medicine

Bryce J. B. Nelson,Jan D. Andersson,Frank Wuest,John Wilson

doi:10.1038/s41598-020-79198-x

Bryce J. B. Nelson, Jan D. Andersson + Show 2 more

Open Access

https://doi.org/10.1038/s41598-020-79198-x

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Journal: Scientific Reports	Publication Date: Dec 1, 2020
Citations: 21	License type: open-access

Affiliation: University of Alberta, Alberta Health Services

Abstract

This study reports the high-yield production of a novel 133/135La theranostic pair at a 22 MeV proton beam energy as an attractive alternative to the recently introduced 132/135La pair, demonstrating over an order of magnitude production increase of 133/135La (231 ± 8 MBq 133La and 166 ± 5 MBq 135La at End of Bombardment (EOB)) compared to 11.9 MeV production of 132/135La (0.82 ± 0.06 MBq 132La and 19.0 ± 1.2 MBq 135La) for 500 µA·min irradiations. A new sealed solid cyclotron target is introduced, which is fast to assemble, easy to handle, storable, and contains reusable components. Radiolabeling with macrocyclic chelators DOTA and macropa achieved full incorporation, with respective apparent 133La molar activites of 33 ± 5 GBq/µmol and 30 ± 4 GBq/µmol. PET centers with access to a 22 MeV capable cyclotron could produce clinically-relevant doses of 133/135La, via natBa irradiation, as a standalone theranostic agent for PET imaging and Auger electron therapy. With lower positron energies and less energetic and abundant gamma rays than 68Ga, 44Sc and 132La, 133La appears to be an attractive radiometal candidate for PET applications requiring a higher scanning resolution, a relatively long isotopic half-life, ease of handling, and a low patient dose.

Highlights

This study reports the high-yield production of a novel 133/135La theranostic pair at a 22 MeV proton beam energy as an attractive alternative to the recently introduced 132/135La pair, demonstrating over an order of magnitude production increase of 133/135La (231 ± 8 MBq 133La and 166 ± 5 MBq 135La at End of Bombardment (EOB)) compared to 11.9 MeV production of 132/135La (0.82 ± 0.06 MBq 132La and 19.0 ± 1.2 MBq 135La) for 500 μA·min irradiations
A recently developed theranostic pair is 132/135La, where positron emissions from 132La are used for PET imaging while the Auger electrons from 135La have the potential for use in Auger electron therapy (AET)[5,6,7]
NIST traceable γ-ray sources used for high-purity germanium detector (HPGe) energy and efficiency calibration were acquired from Eckert & Ziegler Isotopes (Valencia, California, USA)

Summary

Introduction

This study reports the high-yield production of a novel 133/135La theranostic pair at a 22 MeV proton beam energy as an attractive alternative to the recently introduced 132/135La pair, demonstrating over an order of magnitude production increase of 133/135La (231 ± 8 MBq 133La and 166 ± 5 MBq 135La at End of Bombardment (EOB)) compared to 11.9 MeV production of 132/135La (0.82 ± 0.06 MBq 132La and 19.0 ± 1.2 MBq 135La) for 500 μA·min irradiations. PET centers with access to a 22 MeV capable cyclotron could produce clinically-relevant doses of 133/135La, via natBa irradiation, as a standalone theranostic agent for PET imaging and Auger electron therapy. Auger electron-emitting isotopes have potential as a high linear energy transfer (LET) therapeutic agent to destroy cancer cells by depositing their ionizing emission energy over a very short path length, damaging DNA by inducing various types of DNA damage, including double-strand breaks. This holds advantages over lower LET therapy such as β- therapy where emissions can travel over 1 cm, and may unnecessarily irradiate healthy tissue[2, 3].

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