99mTechnetium-or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agents

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art_CAMACHO_99mTechnetiumor_Cy7Labeled_FabTocilizumab_as_Potential_Multiple_Myeloma_Imaging_2021.PDF (3.13 MB)
Citações na Scopus
3
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BENTHAM SCIENCE PUBL LTD
Autores
CAMACHO, Ximena
PERRONI, Carolina
GARCIA, Maria F.
FERNANDEZ, Marcelo
ODDONE, Natalia
BENECH, Juan
Citação
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v.21, n.14, p.1883-1893, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Multiple Myeloma (MM) is a malignant hematologic disorder and the second most common blood cancer. Interleukin-6 (IL-6) has been identified as a crucial factor for the proliferation and survival of MM cells and the overexpression of IL-6 receptor is being studied as a molecular target for therapeutic and diagnostic use in myelomas and other comorbidities. Tocilizumab is a humanized monoclonal antibody that binds IL-6R. Objective: We aim to label and evaluate Fab(Tocilizumab) with 99mTechnetium or Cy7 as potential MM imaging agents. Methods: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37 degrees C, derivatized with NHS-HYNIC-Tfa and radiolabeled with Tc-99m. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h. Results: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with Tc-99m via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i. Conclusion: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary.
Palavras-chave
Fab(Tocilizumab), molecular imaging, IL-6R, multiple myeloma, (99m)Technetium- or Cy7-lableled Fab(Tocilizumab)
URI
https://observatorio.fm.usp.br/handle/OPI/41377
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - LIM/43
Artigos e Materiais de Revistas Científicas - ODS/03