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

Cosby, Alexia G.; Arino, Trevor; Bailey, Tyler A.; Buerger, Matthew; Woods, Joshua J.; Aguirre Quintana, Luis M.; Alvarenga Vasquez, Jennifer V.; Wacker, Jennifer N.; Gaiser, Alyssa N.; Strong, Roland K.; Abergel, Rebecca J.

doi:10.1039/d3cb00050h

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

Journal Article · Thu Jun 15 00:00:00 EDT 2023 · RSC Chemical Biology

DOI:https://doi.org/10.1039/d3cb00050h· OSTI ID:1985319

^[1]; Arino, Trevor ^[2]; ^[2]; Buerger, Matthew ^[3]; ^[1]; ^[1]; Alvarenga Vasquez, Jennifer V. ^[1]; ^[1]; Gaiser, Alyssa N. ^[1]; Strong, Roland K. ^[3]; ^[2]

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); University of California, Berkeley, CA (United States)
Fred Hutchinson Cancer Center, Seattle, WA (United States)

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⁻, t_1/2 = 64 h)/⁸⁶Y (β⁺, t_1/2 = 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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division (CSGB)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1985319

Alternate ID(s):: OSTI ID: 2997073

Journal Information:: RSC Chemical Biology, Journal Name: RSC Chemical Biology Journal Issue: 8 Vol. 4; ISSN 2633-0679

Publisher:: Royal Society of Chemistry (RSC)Copyright Statement

Country of Publication:: United States

Language:: English

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