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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCAMACHO, Ximena
dc.contributor.authorPERRONI, Carolina
dc.contributor.authorMACHADO, Camila L.
dc.contributor.authorCARNEIRO, Camila de Godoi
dc.contributor.authorJUNQUEIRA, Mara de Souza
dc.contributor.authorFARIA, Daniele
dc.contributor.authorGARCIA, Maria F.
dc.contributor.authorFERNANDEZ, Marcelo
dc.contributor.authorODDONE, Natalia
dc.contributor.authorBENECH, Juan
dc.contributor.authorBUCHPIGUEL, Carlos A.
dc.contributor.authorCERECETTO, Hugo
dc.contributor.authorCHAMMAS, Roger
dc.contributor.authorRIVA, Eloisa
dc.contributor.authorCABRAL, Pablo
dc.contributor.authorGAMBINI, Juan P.
dc.date.accessioned2021-08-13T15:12:48Z
dc.date.available2021-08-13T15:12:48Z
dc.date.issued2021
dc.description.abstractBackground: 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.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipAgencia Nacional de Innovacion e Investigacion (Uruguay) [POS_NAC_2015_1_109490]
dc.description.sponsorshipComision Sectorial de Investigacion CientificaUniversidad de la Republica (Uruguay) [24060000014818, 00401000248816]
dc.identifier.citationANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v.21, n.14, p.1883-1893, 2021
dc.identifier.doi10.2174/1871520621999210104181238
dc.identifier.eissn1875-5992
dc.identifier.issn1871-5206
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/41377
dc.language.isoeng
dc.publisherBENTHAM SCIENCE PUBL LTDeng
dc.relation.ispartofAnti-Cancer Agents in Medicinal Chemistry
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright BENTHAM SCIENCE PUBL LTDeng
dc.subjectFab(Tocilizumab)eng
dc.subjectmolecular imagingeng
dc.subjectIL-6Reng
dc.subjectmultiple myelomaeng
dc.subject(99m)Technetium- or Cy7-lableled Fab(Tocilizumab)eng
dc.subject.otherbreast-cancer xenograftseng
dc.subject.otherextramedullary plasmacytomaeng
dc.subject.othermonoclonal-antibodieseng
dc.subject.otherinterleukin-6 il-6eng
dc.subject.otherboneeng
dc.subject.othertocilizumabeng
dc.subject.otherreceptoreng
dc.subject.othertherapyeng
dc.subject.othertc-99meng
dc.subject.otherpathogenesiseng
dc.subject.wosOncologyeng
dc.subject.wosChemistry, Medicinaleng
dc.title99mTechnetium-or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agentseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryUruguai
hcfmusp.affiliation.countryisouy
hcfmusp.author.externalCAMACHO, Ximena:Univ Republica, Fac Ciencias, Ctr Invest Nucl, Dept Radiofarm, Mataojo 2055,PO 11400, Montevideo, Uruguay
hcfmusp.author.externalPERRONI, Carolina:Univ Republica, Fac Ciencias, Ctr Invest Nucl, Dept Radiofarm, Mataojo 2055,PO 11400, Montevideo, Uruguay
hcfmusp.author.externalGARCIA, Maria F.:Univ Republica, Fac Ciencias, Ctr Invest Nucl, Dept Radiofarm, Mataojo 2055,PO 11400, Montevideo, Uruguay
hcfmusp.author.externalFERNANDEZ, Marcelo:Univ Republica, Fac Ciencias, Ctr Invest Nucl, Dept Radiofarm, Mataojo 2055,PO 11400, Montevideo, Uruguay
hcfmusp.author.externalODDONE, Natalia:Inst Invest Biol Clemente Estable, Lab Senalizac Celular & Nanobiol, Montevideo, Uruguay
hcfmusp.author.externalBENECH, Juan:Inst Invest Biol Clemente Estable, Lab Senalizac Celular & Nanobiol, Montevideo, Uruguay
hcfmusp.author.externalCERECETTO, Hugo:Univ Republica, Fac Ciencias, Ctr Invest Nucl, Dept Radiofarm, Mataojo 2055,PO 11400, Montevideo, Uruguay
hcfmusp.author.externalRIVA, Eloisa:Univ Republica, Fac Med, Hosp Clin, Clin Hematol, Montevideo, Uruguay
hcfmusp.author.externalCABRAL, Pablo:Univ Republica, Fac Ciencias, Ctr Invest Nucl, Dept Radiofarm, Mataojo 2055,PO 11400, Montevideo, Uruguay
hcfmusp.author.externalGAMBINI, Juan P.:Univ Republica, Fac Med, Hosp Clin, Ctr Med Nucl & Imagenol Mol, Montevideo, Uruguay
hcfmusp.citation.scopus3
hcfmusp.contributor.author-fmusphcCAMILA MARIA LONGO MACHADO
hcfmusp.contributor.author-fmusphcCAMILA DE GODOI CARNEIRO
hcfmusp.contributor.author-fmusphcMARA DE SOUZA JUNQUEIRA
hcfmusp.contributor.author-fmusphcDANIELE DE PAULA FARIA
hcfmusp.contributor.author-fmusphcCARLOS ALBERTO BUCHPIGUEL
hcfmusp.contributor.author-fmusphcROGER CHAMMAS
hcfmusp.description.beginpage1883
hcfmusp.description.endpage1893
hcfmusp.description.issue14
hcfmusp.description.volume21
hcfmusp.origemWOS
hcfmusp.origem.pubmed33397271
hcfmusp.origem.scopus2-s2.0-85111112098
hcfmusp.origem.wosWOS:000674433600011
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hcfmusp.publisher.countryU ARAB EMIRATESeng
hcfmusp.relation.referenceABRAMS MJ, 1990, J NUCL MED, V31, P2022eng
hcfmusp.relation.referenceAnderson KC, 2011, ANNU REV PATHOL-MECH, V6, P249, DOI 10.1146/annurev-pathol-011110-130249eng
hcfmusp.relation.referenceAngtuaco EJC, 2004, RADIOLOGY, V231, P11, DOI 10.1148/radiol.2311020452eng
hcfmusp.relation.referenceBehr TM, 1998, EUR J NUCL MED, V25, P201, DOI 10.1007/s002590050216eng
hcfmusp.relation.referenceBoswell CA, 2007, NUCL MED BIOL, V34, P757, DOI 10.1016/j.nucmedbio.2007.04.001eng
hcfmusp.relation.referenceBurger R, 2013, TRANSFUS MED HEMOTH, V40, P336, DOI 10.1159/000354194eng
hcfmusp.relation.referenceCalzada Victoria, 2016, Anticancer Agents Med Chem, V16, P1184eng
hcfmusp.relation.referenceCamacho X., 2014, J ANAL ONCOL, V3, P53, DOI [10.6000/1927-7229.2014.03.01.9, DOI 10.6000/1927-7229.2014.03.01.9]eng
hcfmusp.relation.referenceCamacho X, 2017, ANTI-CANCER AGENT ME, V17, P1267, DOI 10.2174/1871520617666170213144917eng
hcfmusp.relation.referenceCamacho X, 2013, CURR RADIOPHARM, V6, P12, DOI 10.2174/1874471011306010003eng
hcfmusp.relation.referenceCarnacho X, 2017, ONCOLOGY-BASEL, V92, P229, DOI 10.1159/000452419eng
hcfmusp.relation.referenceCheng Z, 2006, BIOCONJUGATE CHEM, V17, P662, DOI 10.1021/bc050345ceng
hcfmusp.relation.referenceDimopoulos MA, 2000, BLOOD, V96, P2037eng
hcfmusp.relation.referenceDURIE BGM, 1975, CANCER, V36, P842, DOI 10.1002/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-Ueng
hcfmusp.relation.referenceFontan C, 2015, J LABELLED COMPD RAD, V58, P274, DOI 10.1002/jlcr.3283eng
hcfmusp.relation.referenceGarcia MF, 2014, CURR RADIOPHARM, V7, P84, DOI 10.2174/1874471007666141128160449eng
hcfmusp.relation.referenceGILL SC, 1989, ANAL BIOCHEM, V182, P319, DOI 10.1016/0003-2697(89)90602-7eng
hcfmusp.relation.referenceGiuliani N, 2011, CANCER MICROENVIRON, V4, P325, DOI 10.1007/s12307-011-0072-9eng
hcfmusp.relation.referenceHameed A., 2015, J CANC ALLIED SPEC, V1, P2eng
hcfmusp.relation.referenceHawrysz DJ, 2000, NEOPLASIA, V2, P388, DOI 10.1038/sj.neo.7900118eng
hcfmusp.relation.referenceHideshima T, 2007, NAT REV CANCER, V7, P585, DOI 10.1038/nrc2189eng
hcfmusp.relation.referenceHNATOWICH DJ, 1994, NUCL MED BIOL, V21, P1035, DOI 10.1016/0969-8051(94)90175-9eng
hcfmusp.relation.referenceHunter CA, 2015, NAT IMMUNOL, V16, P448, DOI 10.1038/ni.3153eng
hcfmusp.relation.referenceHussong JW, 1999, AM J CLIN PATHOL, V111, P111eng
hcfmusp.relation.referenceINOUE K, 1994, BLOOD, V84, P2672, DOI 10.1182/blood.V84.8.2672.bloodjournal8482672eng
hcfmusp.relation.referenceJURISSON S, 1993, CHEM REV, V93, P1137, DOI 10.1021/cr00019a013eng
hcfmusp.relation.referenceKatzel JA, 2007, CA-CANCER J CLIN, V57, P301, DOI 10.3322/CA.57.5.301eng
hcfmusp.relation.referenceKawaguchi T, 2014, J CLIN ONCOL, V32, P1902, DOI 10.1200/JCO.2013.52.4694eng
hcfmusp.relation.referenceKe S, 2003, CANCER RES, V63, P7870eng
hcfmusp.relation.referenceKovalchuk AL, 2002, P NATL ACAD SCI USA, V99, P1509, DOI 10.1073/pnas.022643999eng
hcfmusp.relation.referenceKyle RA, 2009, LEUKEMIA, V23, P3, DOI 10.1038/leu.2008.291eng
hcfmusp.relation.referenceLINDMO T, 1984, J IMMUNOL METHODS, V72, P77, DOI 10.1016/0022-1759(84)90435-6eng
hcfmusp.relation.referenceLoening Andreas Markus, 2003, Mol Imaging, V2, P131, DOI 10.1162/153535003322556877eng
hcfmusp.relation.referenceMalpas J.S., 1995, MYELOMA BIOL MANAGEM, P169eng
hcfmusp.relation.referenceMeszaros LK, 2010, INORG CHIM ACTA, V363, P1059, DOI 10.1016/j.ica.2010.01.009eng
hcfmusp.relation.referenceMihara M, 2005, INT IMMUNOPHARMACOL, V5, P1731, DOI 10.1016/j.intimp.2005.05.010eng
hcfmusp.relation.referenceNishimoto N., 2008, V181, P151eng
hcfmusp.relation.referenceNishimoto N, 2008, BLOOD, V112, P3959, DOI 10.1182/blood-2008-05-155846eng
hcfmusp.relation.referenceOlmos RAV, 2014, Q J NUCL MED MOL IM, V58, P207eng
hcfmusp.relation.referenceGambini JP, 2016, CLIN TRANSL IMAGING, V4, P343, DOI 10.1007/s40336-016-0198-3eng
hcfmusp.relation.referencePratt G, 2002, J CLIN PATHOL-MOL PA, V55, P273, DOI 10.1136/mp.55.5.273eng
hcfmusp.relation.referenceRaab MS, 2009, LANCET, V374, P324, DOI 10.1016/S0140-6736(09)60221-Xeng
hcfmusp.relation.referenceREILLY RM, 1995, CLIN PHARMACOKINET, V28, P126, DOI 10.2165/00003088-199528020-00004eng
hcfmusp.relation.referenceRennen HJJM, 2000, NUCL MED BIOL, V27, P599, DOI 10.1016/S0969-8051(00)00134-7eng
hcfmusp.relation.referenceSans-Sebrafen J., 2006, HEMATOLOGIA CLIN, V5theng
hcfmusp.relation.referenceScollard DA, 2011, NUCL MED BIOL, V38, P129, DOI 10.1016/j.nucmedbio.2010.06.010eng
hcfmusp.relation.referenceShain KH, 2009, CANCER RES, V69, P1009, DOI 10.1158/0008-5472.CAN-08-2419eng
hcfmusp.relation.referenceSteiner M, 2011, CLIN CANCER RES, V17, P6406, DOI 10.1158/1078-0432.CCR-11-0483eng
hcfmusp.relation.referenceTang Y, 2005, NUCL MED COMMUN, V26, P427, DOI 10.1097/00006231-200505000-00006eng
hcfmusp.relation.referenceTang Y, 2005, NUCL MED BIOL, V32, P51, DOI 10.1016/j.nucmedbio.2004.08.003eng
hcfmusp.relation.referenceTanisaka H, 2008, BIOCONJUGATE CHEM, V19, P109, DOI 10.1021/bc7001665eng
hcfmusp.relation.referenceTerpos E, 2011, J CLIN ONCOL, V29, P1907, DOI 10.1200/JCO.2010.32.5449eng
hcfmusp.relation.referencevan Dongen GAMS, 2007, ONCOLOGIST, V12, P1379, DOI 10.1634/theoncologist.12-12-1379eng
hcfmusp.relation.referenceVANKUPPEVELD FJM, 1994, APPL ENVIRON MICROB, V60, P149, DOI 10.1128/AEM.60.1.149-152.1994eng
hcfmusp.relation.referenceWILTSHAW E, 1976, MEDICINE, V55, P217, DOI 10.1097/00005792-197605000-00002eng
hcfmusp.relation.referenceWu AM, 2008, CANCER J, V14, P191, DOI 10.1097/PPO.0b013e31817b07aeeng
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