<sup>177</sup>Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM-1 scFv-Fc fusion protein in soft tissue sarcoma.

Details

Ressource 1Request a copy Sous embargo indéterminé.
State: Public
Version: author
License: Not specified
Serval ID
serval:BIB_4E04534CDA56
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
<sup>177</sup>Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM-1 scFv-Fc fusion protein in soft tissue sarcoma.
Journal
EJNMMI research
Author(s)
Delage J.A., Faivre-Chauvet A., Fierle J.K., Gnesin S., Schaefer N., Coukos G., Dunn S.M., Viertl D., Prior J.O.
ISSN
2191-219X (Print)
ISSN-L
2191-219X
Publication state
Published
Issued date
17/08/2020
Peer-reviewed
Oui
Volume
10
Number
1
Pages
98
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
TEM-1 (tumor endothelial marker-1) is a single-pass transmembrane cell surface glycoprotein expressed at high levels by tumor vasculature and malignant cells. We aimed to perform a preclinical investigation of a novel anti-TEM-1 scFv-Fc fusion antibody, 1C1m-Fc, which was radiolabeled with <sup>177</sup> Lu for use in soft tissue sarcomas models.
1C1m-Fc was first conjugated to p-SCN-Bn-DOTA using different excess molar ratios and labeled with <sup>177</sup> Lu. To determine radiolabeled antibody immunoreactivity, Lindmo assays were performed. The in vivo behavior of [177Lu]Lu-1C1m-Fc was characterized in mice bearing TEM-1 positive (SK-N-AS) and negative (HT-1080) tumors by biodistribution and single-photon emission SPECT/CT imaging studies. Estimated organ absorbed doses were obtained based on biodistribution results.
The DOTA conjugation and the labeling with <sup>177</sup> Lu were successful with a radiochemical purity of up to 95%. Immunoreactivity after radiolabeling was 86% ± 4%. Biodistribution showed a specific uptake in TEM-1 positive tumor versus liver as critical non-specific healthy organ, and this specificity is correlated to the number of chelates per antibody. A 1.9-fold higher signal at 72 h was observed in SPECT/CT imaging in TEM-1 positive tumors versus control tumors.
TEM-1 is a promising target that could allow a theranostic approach to soft-tissue sarcoma, and 1C1m-Fc appears to be a suitable targeting candidate. In this study, we observed the influence of the ratio DOTA/antibody on the biodistribution. The next step will be to investigate the best conjugation to achieve an optimal tumor-to-organ radioactivity ratio and to perform therapy in murine xenograft models as a prelude to future translation in patients.
Keywords
1C1m-Fc, CD-248, DOTA conjugation, Soft-tissue sarcoma, TEM-1, Theranostic
Pubmed
Open Access
Yes
Create date
18/08/2020 9:40
Last modification date
29/08/2020 6:20
Usage data