Labeling anti-HER2/neu Monoclonal Antibodies with 111In and 90Y Using a Bifunctional DTPA Chelating Agent
| Autor: | Jerry J. Stastny, Martin W. Brechbiel, Michael J. Blend, Steven M. Swanson |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
Immunoconjugates Receptor ErbB-2 medicine.drug_class Breast Neoplasms Monoclonal antibody Isothiocyanates Trastuzumab hemic and lymphatic diseases Tumor Cells Cultured medicine Humans Yttrium Radioisotopes Radiology Nuclear Medicine and imaging skin and connective tissue diseases Receptor Pharmacology biology Chemistry Indium Radioisotopes Antibodies Monoclonal Stereoisomerism General Medicine Pentetic Acid Molecular biology In vitro Oncology Cell culture Immunoglobulin G Isotope Labeling Monoclonal biology.protein Female Antibody Linker medicine.drug |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 18:355-363 |
| ISSN: | 1557-8852 1084-9785 |
| Popis: | The goal of this investigation was to develop stable radioimmunoconjugates (RICs) of anti-HER2/neu monoclonal antibodies (MoAbs) for imaging and therapy in an animal model bearing human breast tumor xenografts that express normal (MCF-7 cells) and increased amounts of HER2/neu receptors (HCC-1954, BT-474, SKBR-3 cells) on their cell surface membranes. Pharmacy-grade Herceptin, a murine anti-HER2/neu MoAb, and nonspecific mouse IgG protein were conjugated with the recently developed DTPA linker known as CHX-A"-DTPA. These immunoconjugates were labeled with (111)InCl(3) and (90)YCl(3). Using a molar excess of 10:1 CHX-A"-DTPA to immunoglobulin, average specific activities of 1.87 microCi (111)In/microg RIC and 2.71 microCi (90)Y/microg RIC were obtained. The purity of RICs was 96%+ for (111)In and 99%+ for (90)Y. Stability in human plasma at 37 degrees C for both RICs ranged from 98% at 24 h to 85% at 96 h. Binding capacity of the RICs was tested with human cancer cell lines MCF-7, HCC-1954, BT-474, and SKBR-3. Using (111)In-labeled nonspecific IgG protein as a control, (111)In-Herceptin RIC was found to bind to MCF-7 cells with a ratio of 2.5:1 and to SKBR-3 cells with a ratio of 85:1 after 3 h of incubation. (111)In anti-HER2/neu RIC bound to MCF-7 cells with a ratio of 6:1 and to SKBR-3 cells with a ratio of 115:1 after 3 h of incubation. (90)Y-anti-HER2/neu RIC bound 10-times greater to BT-474 cells than to MCF-7 cells. Thus, these MoAbs can be labeled with (111)In and (90)Y using the CHX-A"-DTPA linker. The resulting RICs ((111)In- and (90)Y-anti HER2/neu antibodies) are stable and bind significantly to HER2 overexpressing tumor cell lines. |
| Databáze: | OpenAIRE |
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