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Localization of /sup 131/I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy

Journal Article · · J. Clin. Invest.; (United States)
DOI:https://doi.org/10.1172/JCI111175· OSTI ID:6727100

33 patients with advanced malignant melanoma were studied after intravenous administration of /sup 131/I-labeled Fab fragments specific for p97, an oncofetal glycoprotein of human melanoma. In all, 47 gamma camera imaging studies were performed for the purpose of localization of metastatic deposits. In addition to tumor, /sup 131/I-Fab uptake was also seen in liver and kidney. 20 of these studies included simultaneous administration of both an /sup 131/I-labeled Fab specific for p97, and an /sup 125/I-labeled Fab not specific for p97. Blood clearance of p97-specific Fab was significantly more rapid than for nonspecific Fab. Eight of these patients had biopsies of subcutaneous nodules at 48 and 72 h postinjection in order to assess whether localization of radioactivity was antigen specific. Antigen-specific localization was observed with average ratios of specific/nonspecific uptake of 3.7 (48 h) and 3.4 (72 h); uptake was strongly correlated with tumor p97 concentration (r . 0.81, P less than 0.01). Also, imaging studies of the bio-distribution of /sup 131/I-labeled anti-p97 Fab in patients selected for high p97 tumor concentration showed avid tumor uptake and more prolonged retention of labeled Fab in tumor than in normal tissues. Based on these studies, we estimated that total /sup 131/I doses of 500 mCi could be safely given to patients before dose-limiting toxicity would be observed.

Research Organization:
Veterans Administration Medical Center, Seattle, WA
OSTI ID:
6727100
Journal Information:
J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 72:6; ISSN JCINA
Country of Publication:
United States
Language:
English

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