期刊
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
卷 23, 期 5, 页码 619-631出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/cbr.2008.0493
关键词
monoclonal antibody; EGFR; radioimmunodiagnosis; radioimmunotherapy
类别
资金
- NIH
- National Cancer Institute
- Center for Cancer Research (Bethesda, MD)
The monoclonal antibody, cetuximab, binds to epidermal growth-factor receptor and thus provides all. opportunity to create both imaging and therapies that target this receptor. The potential of cetuximab as a radioimmunoconjugate, using the acyclic bifunctional chelator, CHX-A-DTPA, was investigated. The pharmacokinetic behavior in the blood was determined in mice with and without tumors. Tumor targeting and scintigraphic imaging were evaluated in mice bearing xenografts of LS-174T (colorectal), SHAW (pancreatic), SKOV3 (ovarian), DU145 (prostate), and HT-29 (colorectal). Excellent tumor targeting was observed in each of the models with peak tumor uptakes of 59.8 +/- 18.1, 22.5 +/- 4.7, 33.3 +/- 5.7, 18.2 +/- 7.8, and 41.7 +/- 10.8 injected dose per gram (%ID/g) at 48-72 hours, respectively. In contrast, the highest tumor %ID/g obtained in mice bearing melanoma (A375) xenografts was 6.3 +/- 1.1 at 72 hours. The biodistribution of In-111-cetuximab was also evaluated in nontumor-bearing mice. The highest %ID/g was observed in the liver (9.3 +/- 1.3 at 24 hours) and the salivary glands (8.1 +/- 2.8 at 72 hours). Scintigraphy showed excellent tumor targeting at 24 hours. Blood pool was evident, as expected, but cleared over time. At 168 hours, the tumor was clearly discernible with negligible background.
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