Radioimmunoscintigraphy of Human Met-Expressing Tumor Xenografts Using Met3, a New Monoclonal Antibody
Purpose: Inappropriate expression of the receptor tyrosine kinase Met and its ligand is associated with an aggressive phenotype and poor clinical prognosis for a wide variety of solid human tumors. We are developing imaging and therapeutic agents that target this receptor-ligand complex. In this stu...
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Published in | Clinical cancer research Vol. 9; no. 10; pp. 3839s - 44S |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Association for Cancer Research
01.09.2003
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Subjects | |
Online Access | Get full text |
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Summary: | Purpose: Inappropriate expression of the receptor tyrosine kinase Met and its ligand is associated with an aggressive phenotype and
poor clinical prognosis for a wide variety of solid human tumors. We are developing imaging and therapeutic agents that target
this receptor-ligand complex. In this study, we evaluated the ability of radioiodinated anti-Met monoclonal antibodies from
a single hybridoma clone to image human Met-expressing tumor xenografts.
Experimental Design: Xenografts of four different tissue origins were raised s.c. in host athymic nude mice. Animals received i.v. injections
of I-125-Met3, posterior total body gamma camera images were acquired for several days after injection, and quantitative region-of-interest
activity analysis was performed.
Results: The autocrine Met-expressing tumors S-114 and SK-LMS-1/HGF and the paracrine Met-expressing human prostate carcinoma PC-3
were satisfactorily imaged with I-125-Met3. By region-of-interest analysis, mean initial tumor-associated activities in S-114,
SK-LMS-1/HGF, and PC-3 were 18.6 ± 2.1, 7.2 ± 2.2, and 5.4 ± 2.6% estimated injected activity, and the mean ratios of tumor:total
body activity at 3 days after injection were 0.32 ± 0.13, 0.15 ± 0.06, and 0.10 ± 0.04, respectively. Human melanoma xenografts,
however, accounted for ≤3% of injected or total body activity. We observed a direct rank order correlation between relative
levels of Met3-derived radioactivity in xenografts and relative quantities of Met expressed by the respective cultured tumor
cell lines.
Conclusions: We conclude that I-125-Met3 is effective for imaging human Met-expressing xenografts of different tissue origins, and we
infer that I-125-Met3 distinguishes human tumor xenografts according to their levels of Met expression. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1078-0432 1557-3265 |