Radioimmunotargeting of human rhabdomyosarcoma using monoclonal antibody 8H9 Journal Article
| Authors: | Modak, S.; Guo, H. F. ; Humm, J. L.; Smith-Jones, P. M.; Larson, S. M.; Cheung, N. K. V. |
| Article Title: | Radioimmunotargeting of human rhabdomyosarcoma using monoclonal antibody 8H9 |
| Abstract: | Although metastatic rhabdomyosarcoma (RMS) is chemotherapy and radiotherapy responsive, few patients are cured. 8H9, a murine IgG1 monoclonal antibody, recognizes a unique cell surface tumor antigen broadly distributed on neuroectodermal, epithelial, and mesenchymal tumors, including RMS. We now report on the in vitro characterization of radiolabeled 8H9 and its in vivo immunotargeting potential in mice with subcutaneous human RMS. Saturation-binding studies carried out to determine 125I-8H9 affinity to the RMS cell line HTB82 demonstrated that 125I-8H9 had a K d of 10.3nM with an estimated 115,000 binding sites on every HTB82 cell. 125I-8H9 was retained on the cell surface without significant internalization. Biodistribution of 125I-8H9 was studied in athymic mice bearing HTB82 xenografts. Following intravenous injection of 4.44MBq of 125I-8H9, selective tumor uptake was evident 4 to 172 hours after injection. Average tumor uptake was 7.0 ± 1.8, 11.5 ± 3.9, 15.1 ± 3.7, and 5.4 ± 1.2% injected dose per gram at 4, 24, 48, and 172 hours, respectively. Mean tumor: tissue ratios were maximal at 172 hours (for lung, 4, kidney, 6, liver, 7, spleen, 11, femur, 14, muscle, 18, and brain, 48). Established RMS xenografts treated with a single injection of 18.5 MBq 131I-8H9 were significantly suppressed compared to controls. Radiolabeled 8H9 effectively targeted RMS xenografts and may have a potential clinical role in radioimmunotherapy. © Mary Ann Liebert, Inc. |
| Keywords: | immunohistochemistry; controlled study; unclassified drug; human cell; nonhuman; binding affinity; mouse; animals; mice; lung neoplasms; animal experiment; animal model; protein binding; cell line, tumor; mice, inbred balb c; time factors; monoclonal antibody; antibodies, monoclonal; kinetics; immunoglobulin g; iodine 125; iodine 131; drug distribution; drug uptake; isotope labeling; xenograft; nude mouse; tissue distribution; iodine radioisotopes; mice, nude; antigen recognition; neoplasm metastasis; neoplasm transplantation; epithelium; rhabdomyosarcoma; radioimmunotherapy; neuroectoderm tumor; epithelium tumor; immunoglobulin g1 antibody; drug binding; carcinoma, small cell; radioimmunodetection; mesenchymoma; monoclonal antibody 8h9; pediatric solid tumors; tosylchloramide sodium |
| Journal Title: | Cancer Biotherapy and Radiopharmaceuticals |
| Volume: | 20 |
| Issue: | 5 |
| ISSN: | 1084-9785 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2005-10-01 |
| Start Page: | 534 |
| End Page: | 546 |
| Language: | English |
| DOI: | 10.1089/cbr.2005.20.534 |
| PUBMED: | 16248769 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 24 October 2012" - "CODEN: CBRAF" - "Source: Scopus" |
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