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Triningsih Triningsih
Center for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency Indonesia Nuclear Energy Agency (BATAN)
Astronomy Chemistry Earth & Planetary Sciences Mathematics Physics

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Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancers Treatment Titis Sekar Humani; Sutari Sutari; Triningsih Triningsih; Martalena Ramli; Rien Ritawidya; Ratna Dini Haryuni
Journal of Mathematical and Fundamental Sciences Vol. 49 No. 3 (2017)
Publisher : Institute for Research and Community Services (LPPM) ITB

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.5614/j.math.fund.sci.2017.49.3.4

Abstract

Intact monoclonal antibodies with a high molecular weight tend to have a poor pharmacokinetic profile and tumor penetration, and potential for eliciting host antibody responses. F(ab’)2 fragments smaller than intact monoclonal antibodies that still maintain antigen binding could solve this problem. The objective of this study was to optimize the digestion process of nimotuzumab, an anti-EGFR monoclonal antibody, into its F(ab’)2 fragment and investigate its potential as a therapeutic radioimmunoconjugate. Optimal conditions for digestion of nimotuzumab to its F(ab’)2 fragment were found to be 6 hours of digestion time with a pH of 3.5 and 1:100 mol ratio of pepsin to nimotuzumab. The purity of the F(ab’)2-nimotuzumab was confirmed by SDS-PAGE and HPLC analysis. Prior to its labeling with lutetium-177 radionuclide, the nimotuzumab-F(ab’)2 was conjugated to DOTA-PAMAM dendrimer [DOTA denotes 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, PAMAM denotes poly(amidoamine)] to form conjugate of (DOTA)n-PAMAM-[nimotuzumab-F(ab’)2]. Radiolabeling of DOTA-PAMAM-[nimotuzumab-F(ab’)2] conjugate with 177Lu resulted in (177Lu-DOTA)n-PAMAM-[nimotuzumab-F(ab’)2] with radiochemical purity > 99% after purification with a PD-10 column. Further studies still need to be performed in order to confirm the potential of this radioimmunoconjugate as a radioimmunotherapeutic agent for EGFR overexpressed cancers.
Co-Authors Martalena Ramli Ratna Dini Haryuni Rien Ritawidya Sutari Sutari Titis Sekar Humani