Immuno-PET imaging of tumor endothelial marker 8 (TEM8)
| Autor: | Olga Vasalatiy, Lawrence P. Szajek, Kelly Lane, Peter L. Choyke, Vincent Coble, Elaine M. Jagoda, Chang H. Paik, Biying Xu, Gary L. Griffiths, Mark R. Williams, Veerendra Bhadrasetty, Stephanie Histed, Amit Chaudhary, Karen Wong, Frank Kuo, Osama Elbuluk, Christopher S. Szot, Haitao Wu, Brad St. Croix |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
CD31
Biodistribution CD30 Angiogenesis Blotting Western Pharmaceutical Science Mice Nude Tumor M2-PK Receptors Cell Surface Biology Deferoxamine Antibodies Monoclonal Humanized anti-TEM8 antibodies Article Mice angiogenesis In vivo Neoplasms Drug Discovery Tumor Cells Cultured Animals Humans Immunoprecipitation Tissue Distribution Microfilament Proteins [89Zr]-df−L2mAb L2 Molecular biology Xenograft Model Antitumor Assays Imaging agent Molecular Imaging Neoplasm Proteins immuno-PET imaging Positron-Emission Tomography Molecular Medicine Immunohistochemistry Female Zirconium Radiopharmaceuticals TEM8 |
| Zdroj: | Molecular Pharmaceutics |
| ISSN: | 1543-8392 |
| Popis: | Tumor endothelial marker 8 (TEM8) is a cell surface receptor that is highly expressed in a variety of human tumors and promotes tumor angiogenesis and cell growth. Antibodies targeting TEM8 block tumor angiogenesis in a manner distinct from the VEGF receptor pathway. Development of a TEM8 imaging agent could aid in patient selection for specific antiangiogenic therapies and for response monitoring. In these studies, L2, a therapeutic anti-TEM8 monoclonal IgG antibody (L2mAb), was labeled with (89)Zr and evaluated in vitro and in vivo in TEM8 expressing cells and mouse xenografts (NCI-H460, DLD-1) as a potential TEM8 immuno-PET imaging agent. (89)Zr-df-L2mAb was synthesized using a desferioxamine-L2mAb conjugate (df-L2mAb); (125)I-L2mAb was labeled directly. In vitro binding studies were performed using human derived cell lines with high, moderate, and low/undetectable TEM8 expression. (89)Zr-df-L2mAb in vitro autoradiography studies and CD31 IHC staining were performed with cryosections from human tumor xenografts (NCI-H460, DLD-1, MKN-45, U87-MG, T-47D, and A-431). Confirmatory TEM8 Western blots were performed with the same tumor types and cells. (89)Zr-df-L2mAb biodistribution and PET imaging studies were performed in NCI-H460 and DLD-1 xenografts in nude mice. (125)I-L2mAb and (89)Zr-df-L2mAb exhibited specific and high affinity binding to TEM8 that was consistent with TEM8 expression levels. In NCI-H460 and DLD-1 mouse xenografts nontarget tissue uptake of (89)Zr-df-L2mAb was similar; the liver and spleen exhibited the highest uptake at all time points. (89)Zr-L2mAb was highly retained in NCI-H460 tumors with |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|