Issue 8, 2023

Siderocalin fusion proteins enable a new 86Y/90Y theranostic approach

Abstract

The mammalian protein siderocalin binds bacterial siderophores and their iron complexes through cation-π and electrostatic interactions, but also displays high affinity for hydroxypyridinone complexes of trivalent lanthanides and actinides. In order to circumvent synthetic challenges, the use of siderocalin-antibody fusion proteins is explored herein as an alternative targeting approach for precision delivery of trivalent radiometals. We demonstrate the viability of this approach in vivo, using the theranostic pair 90Y (β, t1/2 = 64 h)/86Y (β+, t1/2 = 14.7 h) in a SKOV-3 xenograft mouse model. Ligand radiolabeling with octadentate hydroxypyridinonate 3,4,3-LI(1,2-HOPO) and subsequent protein binding were achieved at room temperature. The results reported here suggest that the rapid non-covalent binding interaction between siderocalin fusion proteins and the negatively charged Y(III)-3,4,3-LI(1,2-HOPO) complexes could enable purification-free, cold-kit labeling strategies for the application of therapeutically relevant radiometals in the clinic.

Graphical abstract: Siderocalin fusion proteins enable a new 86Y/90Y theranostic approach

Supplementary files

Article information

Article type
Paper
Submitted
05 4 2023
Accepted
02 6 2023
First published
15 6 2023
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2023,4, 587-591

Siderocalin fusion proteins enable a new 86Y/90Y theranostic approach

A. G. Cosby, T. Arino, T. A. Bailey, M. Buerger, J. J. Woods, L. M. Aguirre Quintana, J. V. Alvarenga Vasquez, J. N. Wacker, A. N. Gaiser, R. K. Strong and R. J. Abergel, RSC Chem. Biol., 2023, 4, 587 DOI: 10.1039/D3CB00050H

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