Tocilizumab Labeling with (99m)Technetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma

Imagem de Miniatura
Arquivos
art_CAMACHO_Tocilizumab_Labeling_with_99mTechnetium_via_HYNIC_as_a_2017.PDF (4.54 MB)
Citações na Scopus
4
Tipo de produção
article
Data de publicação
2017
Editora
BENTHAM SCIENCE PUBL LTD
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
CAMACHO, Ximena
GARCIA, Maria Fernanda
FERNANDEZ, Marcelo
ODDONE, Natalia
BENECH, Juan
GAMBINI, Juan Pablo
CERECETTO, Hugo
CABRALA, Pablo
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v.17, n.9, p.1267-1277, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Multiple myeloma is the second most common hematological malignancy. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6. Objective: To radiolabel Tocilizumab with (99m)Technetium as a potential imaging agents for MM. Methods: IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S). Tocilizumab was derivatized with NHS-HYNIC-Tfa and radiolabeling with Tc-99m. Radiochemical stability was determined. In-vitro binding and immunoreactive fraction assays were performed. Biodistribution and SPECT/CT imaging were evaluated in healthy BALB/c and MM-bearing BALB/c nude mice. Results: LCM studies allowed us to demonstrate that U266, NCI-H929 and MM1S cells present high expression of IL-6R in cell membrane. Radiolabeling was carried out in a fast, reproducible, easy and stable way having high radiochemical purity and did not interfere with epitope recognition. The immunoreactive fraction of (TcHYNIC)-Tc-99m-Tocilizumab was 86.35%. Biodistribution showed a high uptake in liver, spleen, gastrointestinal tract and kidneys. SPECT/CT imaging of MM-bearing BALB/c nude mice showed liver uptake and a high tumor selective uptake at 24 hours. Conclusions: Our results support the potential role of 99mTc-HYNIC-Tocilizumb as a novel MM radiotracer for targeting IL-6 expression in-vivo. We describe the development of a formulation kit to radiolabeling monoclonal antibodies in a clinical setting. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for MM disease.
Palavras-chave
Tocilizumab, IL-6R, Tc-99m-HYNIC-tocilizumab, molecular imaging, multiple myeloma
URI
https://observatorio.fm.usp.br/handle/OPI/21856
Referências
  1. ABRAMS MJ, 1990, J NUCL MED, V31, P2022
  2. Akizawa H, 2008, ADV DRUG DELIVER REV, V60, P1319, DOI 10.1016/j.addr.2008.04.005
  3. Anderson KC, 2011, ANNU REV PATHOL-MECH, V6, P249, DOI 10.1146/annurev-pathol-011110-130249
  4. Angtuaco EJC, 2004, RADIOLOGY, V231, P11, DOI 10.1148/radiol.2311020452
  5. Boswell CA, 2007, NUCL MED BIOL, V34, P757, DOI 10.1016/j.nucmedbio.2007.04.001
  6. Camacho X., 2014, J ANAL ONCOL, V3, P53, DOI [10.1159/000338961, DOI 10.1159/000338961]
  7. Camacho X, 2013, CURR RADIOPHARM, V6, P12, DOI 10.2174/1874471011306010003
  8. DURIE BGM, 1975, CANCER, V36, P842, DOI 10.1002/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U
  9. Garcia MF, 2014, CURR RADIOPHARM, V7, P84, DOI 10.2174/1874471007666141128160449
  10. Gotthardt M, 2007, J NUCL MED, V48, P596, DOI 10.2967/jnumed.106.036020
  11. Gutierrez E, 2012, SALUD MILIT, V31, P10
  12. Hameed A., 2015, J CANC ALLIED SPEC, V1, P2
  13. Hideshima T, 2007, NAT REV CANCER, V7, P585, DOI 10.1038/nrc2189
  14. HNATOWICH DJ, 1994, NUCL MED BIOL, V21, P1035, DOI 10.1016/0969-8051(94)90175-9
  15. Hunter CA, 2015, NAT IMMUNOL, V16, P448, DOI 10.1038/ni.3153
  16. INOUE K, 1994, BLOOD, V84, P2672
  17. JURISSON S, 1993, CHEM REV, V93, P1137, DOI 10.1021/cr00019a013
  18. Katzel JA, 2007, CA-CANCER J CLIN, V57, P301, DOI 10.3322/CA.57.5.301
  19. Kawaguchi T, 2014, J CLIN ONCOL, V32, P1902, DOI 10.1200/JCO.2013.52.4694
  20. Kumar SR, 2007, CLIN CANCER RES, V13, P6070, DOI 10.1158/1078-0432.CCR-07-0160
  21. Kyle RA, 2009, LEUKEMIA, V23, P3, DOI 10.1038/leu.2008.291
  22. Lindegren S, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0126298
  23. LINDMO T, 1984, J IMMUNOL METHODS, V72, P77, DOI 10.1016/0022-1759(84)90435-6
  24. Loening Andreas Markus, 2003, Mol Imaging, V2, P131, DOI 10.1162/153535003322556877
  25. Malpas J.S., 1995, MYELOMA BIOL MANAGEM, P169
  26. Meszaros LK, 2010, INORG CHIM ACTA, V363, P1059, DOI 10.1016/j.ica.2010.01.009
  27. Mihara M, 2005, INT IMMUNOPHARMACOL, V5, P1731, DOI 10.1016/j.intimp.2005.05.010
  28. National Cancer Institute, SNAPSH MYEL INC MORT
  29. Nishimoto N., 2008, V181, P151
  30. Nishimoto N, 2008, BLOOD, V112, P3959, DOI 10.1182/blood-2008-05-155846
  31. Onuchic AC, 2012, MEDIAT INFLAMM, DOI 10.1155/2012/175408
  32. Pratt G, 2002, J CLIN PATHOL-MOL PA, V55, P273
  33. Raab MS, 2009, LANCET, V374, P324, DOI 10.1016/S0140-6736(09)60221-X
  34. Rennen HJJM, 2000, NUCL MED BIOL, V27, P599, DOI 10.1016/S0969-8051(00)00134-7
  35. ROGERS BE, 1995, CANCER RES, V55, pS5714
  36. Sans-Sebrafen J., 2006, HEMATOLOGIA CLIN
  37. Shain KH, 2009, CANCER RES, V69, P1009, DOI 10.1158/0008-5472.CAN-08-2419
  38. Stopar TG, 2006, EUR J NUCL MED MOL I, V33, P53, DOI 10.1007/s00259-005-1838-4
  39. Tsai SW, 2001, BIOCONJUGATE CHEM, V12, P264, DOI 10.1021/bcc0000987
  40. van Dongen GAMS, 2007, ONCOLOGIST, V12, P1379, DOI 10.1634/theoncologist.12-12-1379
  41. VANKUPPEVELD FJM, 1994, APPL ENVIRON MICROB, V60, P149
  42. Wu AM, 2008, CANCER J, V14, P191, DOI 10.1097/PPO.0b013e31817b07ae
  43. Yardeni T, 2011, LAB ANIMAL, V40, P155, DOI 10.1038/laban0511-155

Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - LIM/43
Artigos e Materiais de Revistas Científicas - ODS/03