99mTechnetium- or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agents.
99mTechnetium- or Cy7-lableled Fab(Tocilizumab).
Fab(Tocilizumab)
IL-6R
molecular imaging
multiple myeloma
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2021
2021
Historique:
received:
20
04
2020
revised:
07
10
2020
accepted:
01
11
2020
pubmed:
6
1
2021
medline:
18
1
2022
entrez:
5
1
2021
Statut:
ppublish
Résumé
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. We aim to label and evaluate Fab(Tocilizumab) with 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°C, derivatized with NHS-HYNIC-Tfa and radiolabeled with 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 99mTc 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. 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.
Sections du résumé
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
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°C, derivatized with NHS-HYNIC-Tfa and radiolabeled with
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 99mTc 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.
Identifiants
pubmed: 33397271
pii: ACAMC-EPUB-113020
doi: 10.2174/1871520621999210104181238
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Carbocyanines
0
IL6R protein, human
0
Organotechnetium Compounds
0
Radiopharmaceuticals
0
Receptors, Interleukin-6
0
indotricarbocyanine
0
tocilizumab
I031V2H011
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1883-1893Subventions
Organisme : Agencia Nacional de Innovación e Investigación (Uruguay)
ID : POS_NAC_2015_1_109490
Organisme : Comisión Sectorial de Investigación Científica-Universidad de la República (Uruguay)
ID : 240600-000148-18, 004010-002488-16
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.