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European Journal of Nuclear Medicine and Molecular Imaging
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 5/2021

11.11.2020 | Original Article

Development of [89Zr]DFO-elotuzumab for immunoPET imaging of CS1 in multiple myeloma

verfasst von: Anchal Ghai, Alexander Zheleznyak, Matt Mixdorf, Julie O’Neal, Julie Ritchey, Michael Rettig, John DiPersio, Monica Shokeen, Samuel Achilefu

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 5/2021

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Abstract

Purpose

Multiple myeloma (MM) is a bone marrow malignancy that remains mostly incurable. Elotuzumab is an FDA-approved therapeutic monoclonal antibody targeted to the cell surface glycoprotein CS1, which is overexpressed in MM cells. Identifying patients who will respond to CS1-targeted treatments such as elotuzumab requires the development of a companion diagnostic to assess the presence of CS1. Here, we evaluated [89Zr]DFO-elotuzumab as a novel PET tracer for imaging CS1 expression in preclinical MM models.

Methods

Conjugation of desferrioxamine-p-benzyl-isothiocyanate (DFO-Bz-NCS) to elotuzumab enabled zirconium-89 radiolabeling. MM.1S-CG cells were intravenously injected in NOD SCID gamma (NSG) mice. Small animal PET imaging with [89Zr]DFO-elotuzumab (1.11 MBq/mouse, 7 days post-injection), [89Zr]DFO-IgG (1.11 MBq/mouse, 7 days post-injection), and [18F]FDG (7–8 MBq, 1 h post-injection) was performed. Additionally, biodistribution of [89Zr]DFO-elotuzumab post-imaging at 7 days was also done. In vivo specificity of [89Zr]DFO-elotuzumab was further evaluated with a blocking study and ex vivo autoradiography.

Results

[89Zr]DFO-elotuzumab was produced with high specific activity (56 ± 0.75 MBq/nmol), radiochemical purity (99% ± 0.5), and yield (93.3% ± 1.5). Dissociation constant of 40.4 nM and receptor density of 126 fmol/mg was determined in MM.1S-CG cells. Compared to [89Zr]DFO-IgG, [89Zr]DFO-elotuzumab localized with a significantly higher standard uptake value in tumor-bearing bone tissue (8.59 versus 4.77). Blocking with unlabeled elotuzumab significantly reduced (P < 0.05) uptake of [89Zr]DFO-elotuzumab in the bones. Importantly, while [18F]FDG demonstrated similar uptake in the bone and muscle, [89Zr]DFO-elotuzumab showed > 3-fold enhanced uptake in bones.

Conclusion

These data demonstrate the feasibility of [89Zr]DFO-elotuzumab as a companion diagnostic for CS1-targeted therapies.
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Metadaten
Titel
Development of [89Zr]DFO-elotuzumab for immunoPET imaging of CS1 in multiple myeloma
verfasst von
Anchal Ghai
Alexander Zheleznyak
Matt Mixdorf
Julie O’Neal
Julie Ritchey
Michael Rettig
John DiPersio
Monica Shokeen
Samuel Achilefu
Publikationsdatum
11.11.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 5/2021
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-020-05097-y

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