Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek).
Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek).
Related Articles Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek). Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7064s-7069s Authors: Hay RV, Cao B, Skinner RS, Su Y, Zhao P, Gustafson MF, Qian CN, Teh BT, Knudsen BS, Resau JH, Shen S, Waters DJ, Gross MD, Vande Woude GF PURPOSE: Met, an oncogene product and receptor tyrosine kinase, is a keystone molecule for malignant progression in solid human tumors. We are developing Met-directed imaging and therapeutic agents, including anti-Met monoclonal antibodies (MetSeek). In this study, we compared two antibodies, Met5 and Met3, for nuclear imaging of human and canine Met-expressing tumor xenografts in nude mice. EXPERIMENTAL DESIGN: Xenografts representing cancers of three different human tissue origins and metastatic canine prostate cancer were raised s.c. in host athymic nude mice. Animals were injected i.v. with I-125-Met5 or I-125-Met3, posterior total body gamma camera images were acquired for several days postinjection, and quantitative region-of-interest activity analysis was done. RESULTS: PC-3, SK-LMS-1/HGF, and CNE-2 xenografts imaged with I-125-Met5 were compared with PC-3, SK-LMS-1/HGF, and DU145 xenografts imaged with I-125-Met3. Nuclear imaging contrast was qualitatively similar for I-125-Met5 and I-125-Met3 in PC-3 and SK-LMS-1/HGF host mice. However, by region-of-interest analysis, the set of human tumors imaged with I-125-Met3 exhibited a pattern of rapid initial tumor uptake followed by a continuous decline in activity, whereas the set of human tumors imaged with I-125-Met5 showed slow initial uptake, peak tumor-associated activity at 1 day postinjection, and persistence of activity in xenografts for at least 5 days. GN4 canine prostate cancer xenografts were readily imaged with I-125-Met5. CONCLUSIONS: We conclude that radioiodinated Met3 and Met5 offer qualitatively similar nuclear images in xenograft-bearing mice, but quantitative considerations indicate that Met5 might be more useful for radioimmunotherapy. Moreover, canine prostate cancer seems to be a suitable model for second-stage preclinical evaluation of Met5. PMID: 16203803 [PubMed - indexed for MEDLINE]