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Radioimmunoscintigraphy of Human Met-Expressing Tumor Xenografts Using Met3, a New Monoclonal Antibody¹

Van Andel Research Institute, Grand Rapids, Michigan 49503 [R. V. H., B. C., L-M. W., Y. S., J. H. R., M. F. G., H-M. K., G. F. V. W.]; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 [B. S. K.]; and Department of Veterans Affairs Healthcare System, Ann Arbor, Michigan 48105 [R. S. S., M. D. G.]

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.