Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancers Treatment
| Autor: | Sutari Sutari, Triningsih Triningsih, Titis Sekar Humani, Ratna Dini Haryuni, Martalena Ramli, Rien Ritawidya |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
pepsin digestion medicine.drug_class Radioimmunoconjugate EGFR General Mathematics Amidoamine General Physics and Astronomy Monoclonal antibody General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Pharmacokinetics Dendrimer medicine 177Lu-DOTA-PAMAM-[nimotuzumab-F(ab’)2] DOTA Nimotuzumab lcsh:Science lcsh:Science (General) Multidisciplinary nimotuzumab-F(ab’)2 General Chemistry General Medicine Molecular biology 030104 developmental biology chemistry General Earth and Planetary Sciences lcsh:Q dendrimer PAMAM General Agricultural and Biological Sciences lcsh:Q1-390 medicine.drug Conjugate |
| Zdroj: | Journal of Mathematical and Fundamental Sciences, Vol 49, Iss 3, Pp 258-268 (2017) |
| ISSN: | 2338-5510 2337-5760 |
| DOI: | 10.5614/j.math.fund.sci.2017.49.3.4 |
| Popis: | 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 177 Lu resulted in ( 177 Lu-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|