New chelating agent for attaching indium-111 to monoclonal antibodies: in vitro and in vivo evaluation
| Autor: | Richard P. McCabe, M. V. Haspel, S. Shaban, Michael G. Hanna, H. Sidrak, Nicholas Pomato, R. Subramanian, J. Colony |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Biodistribution
Stereochemistry medicine.drug_class Transplantation Heterologous Biomedical Engineering Pharmaceutical Science Mice Nude Bioengineering Monoclonal antibody Immunoscintigraphy Cell Line Mice In vivo medicine Animals Humans Chelation Tissue Distribution Serum Albumin Cell Line Transformed Chelating Agents Pharmacology biology Chemistry Organic Chemistry Indium Radioisotopes Antibodies Monoclonal Pentetic Acid Molecular biology In vitro Immunoglobulin Isotypes Kinetics Immunoglobulin M Colonic Neoplasms biology.protein Indicators and Reagents Antibody Biotechnology Conjugate |
| Zdroj: | Bioconjugate chemistry. 3(3) |
| ISSN: | 1043-1802 |
| Popis: | 111In possesses excellent radiophysical properties suitable for use in immunoscintigraphy of cancerous tissues when attached to an antitumor antibody. However, 111In has a tendency to accumulate in normal tissues such as liver. Instability of the linkage between 111In and antibody may contribute to this problem. To avoid this, we developed a new bifunctional chelating agent, 1,3-bis[N-[N-(2-aminoethyl)-2-aminoethyl]-2-aminoacetamido]-2-(4- isothiocyanatobenzyl)propane-N,N,N',N'',N''',N'''',N''''',N'''''- octaacetic acid (LiLo), that forms a kinetically stable chelate with metal ions such as indium. Using LiLo, indium-111 was conjugated to a human monoclonal antibody, 16.88. Competitive binding analysis revealed that the 16.88-LiLo conjugate is as immunoreactive as the unconjugated native antibody. This conjugate was compared with 111In-16.88, where diethylenetriaminepentaacetic acid dianhydride (DTPAa) was used as the chelating agent. In vitro stability studies showed that 111In was more stably bound to 16.88-LiLo than to 16.88-DTPA. Biodistribution studies in athymic mice bearing colorectal tumor xenografts indicated less liver retention with 16.88-LiLo than with 16.88-DTPA. These results demonstrate that LiLo is superior to DTPAa for attachment of 111In to the monoclonal antibodies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|