当前位置： SCI文献检索 > EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING期刊下所有文献 > Development of [89Zr]DFO-elotuzumab for immunoPET imaging of CS1 in multiple myeloma.

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

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.

journal_name

Eur J Nucl Med Mol Imaging

journal_title

European journal of nuclear medicine and molecular imaging

authors

Ghai A,Zheleznyak A,Mixdorf M,O'Neal J,Ritchey J,Rettig M,DiPersio J,Shokeen M,Achilefu S

doi

10.1007/s00259-020-05097-y

subject

Has Abstract

pub_date

2020-11-11 00:00:00

eissn

1619-7070

issn

1619-7089

pii

10.1007/s00259-020-05097-y

pub_type

杂志文章

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