Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment
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....
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| Format: | Article |
| Language: | English |
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ITB Journal Publisher
2017-12-01
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| Series: | Journal of Mathematical and Fundamental Sciences |
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| Online Access: | http://journals.itb.ac.id/index.php/jmfs/article/view/2375 |
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| author | Titis Sekar Humani Sutari Triningsih Martalena Ramli Rien Ritawidya Ratna Dini Haryuni |
| author_facet | Titis Sekar Humani Sutari Triningsih Martalena Ramli Rien Ritawidya Ratna Dini Haryuni |
| author_sort | Titis Sekar Humani |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T03:57:27Z |
| format | Article |
| id | doaj.art-ee85ea80949f4c5b947b7a11b3f4da66 |
| institution | Directory Open Access Journal |
| issn | 2337-5760 2338-5510 |
| language | English |
| last_indexed | 2024-12-24T03:57:27Z |
| publishDate | 2017-12-01 |
| publisher | ITB Journal Publisher |
| record_format | Article |
| series | Journal of Mathematical and Fundamental Sciences |
| spelling | doaj.art-ee85ea80949f4c5b947b7a11b3f4da662022-12-21T17:16:24ZengITB Journal PublisherJournal of Mathematical and Fundamental Sciences2337-57602338-55102017-12-0149325826810.5614/j.math.fund.sci.2017.49.3.4Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer TreatmentTitis Sekar Humani0Sutari1Triningsih2Martalena Ramli3Rien Ritawidya4Ratna Dini Haryuni5Center for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency (BATAN), PUSPIPTEK Serpong, Building 11, Setu, Tangerang Selatan 15310, IndonesiaCenter for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency (BATAN), PUSPIPTEK Serpong, Building 11, Setu, Tangerang Selatan 15310, IndonesiaCenter for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency (BATAN), PUSPIPTEK Serpong, Building 11, Setu, Tangerang Selatan 15310, IndonesiaCenter for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency (BATAN), PUSPIPTEK Serpong, Building 11, Setu, Tangerang Selatan 15310, IndonesiaCenter for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency (BATAN), PUSPIPTEK Serpong, Building 11, Setu, Tangerang Selatan 15310, IndonesiaCenter for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency (BATAN), PUSPIPTEK Serpong, Building 11, Setu, Tangerang Selatan 15310, IndonesiaIntact 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.http://journals.itb.ac.id/index.php/jmfs/article/view/2375dendrimer PAMAMEGFRnimotuzumab-F(ab’)2pepsin digestion177Lu-DOTA-PAMAM-[nimotuzumab-F(ab’)2] |
| spellingShingle | Titis Sekar Humani Sutari Triningsih Martalena Ramli Rien Ritawidya Ratna Dini Haryuni Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment Journal of Mathematical and Fundamental Sciences dendrimer PAMAM EGFR nimotuzumab-F(ab’)2 pepsin digestion 177Lu-DOTA-PAMAM-[nimotuzumab-F(ab’)2] |
| title | Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment |
| title_full | Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment |
| title_fullStr | Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment |
| title_full_unstemmed | Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment |
| title_short | Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment |
| title_sort | preparation of 177lu dota n pamam nimotuzumab f ab 2 as a therapeutic radioimmunoconjugate for egfr overexpressed cancer treatment |
| topic | dendrimer PAMAM EGFR nimotuzumab-F(ab’)2 pepsin digestion 177Lu-DOTA-PAMAM-[nimotuzumab-F(ab’)2] |
| url | http://journals.itb.ac.id/index.php/jmfs/article/view/2375 |
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