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

Autor:	Camacho X; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay., Perroni C; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay., Machado CL; Nuclear Medicine Medical Investigation Laboratory LIM43-Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo - HCFMUSP, Sao Paulo, Brazil., de Godoi Carneiro C; Nuclear Medicine Medical Investigation Laboratory LIM43-Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo - HCFMUSP, Sao Paulo, Brazil., de Souza Junqueira M; Laboratorio de Oncologia Experimental, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Arnaldo Nº 455- Cerqueira Cesar - CEP: 01246903, Sao Paulo, Brazil., Faria D; Nuclear Medicine Medical Investigation Laboratory LIM43-Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo - HCFMUSP, Sao Paulo, Brazil., García MF; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay., Fernández M; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay., Oddone N; Laboratorio de Senalizacion Celular y Nanobiologia, Instituto de Investigaciones Biologicas Clemente Estable, Montevideo, Uruguay., Benech J; Laboratorio de Senalizacion Celular y Nanobiologia, Instituto de Investigaciones Biologicas Clemente Estable, Montevideo, Uruguay., Buchpiguel CA; Nuclear Medicine Medical Investigation Laboratory LIM43-Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo - HCFMUSP, Sao Paulo, Brazil., Cerecetto H; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay., Chammas R; Laboratorio de Oncologia Experimental, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Arnaldo Nº 455- Cerqueira Cesar - CEP: 01246903, Sao Paulo, Brazil., Riva E; Clinica Hematologica. Hospital de Clinicas. Facultad de Medicina. Universidad de la Republica, Montevideo, Uruguay., Cabral P; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay., Gambini JP; Centro de Medicina Nuclear e Imagenologia Molecular, Hospital de Clinicas, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2021; Vol. 21 (14), pp. 1883-1893.
DOI:	10.2174/1871520621999210104181238
Abstrakt:	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 99m Technetium 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°C, derivatized with NHS-HYNIC-Tfa and radiolabeled with 99m Tc. 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 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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu