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Journal articles
177Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM- 1 scFv-Fc fusion protein in soft tissue sarcoma
Abstract : Purpose: 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 177 Lu for use in soft tissue sarcomas models. Methods: 1C1m-Fc was first conjugated to p-SCN-Bn-DOTA using different excess molar ratios and labeled with 177 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. Results: The DOTA conjugation and the labeling with 177 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. Conclusion: 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.
https://www.hal.inserm.fr/inserm-02923381
Contributor : Elizabeth Bernardo Connect in order to contact the contributor
Submitted on : Thursday, August 27, 2020 - 9:14:35 AM
Last modification on : Wednesday, October 20, 2021 - 3:19:38 AM
Contributor : Elizabeth Bernardo Connect in order to contact the contributor
Submitted on : Thursday, August 27, 2020 - 9:14:35 AM
Last modification on : Wednesday, October 20, 2021 - 3:19:38 AM
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s13550-020-00685-3Eq13.pdf
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