Annals of the New York Academy of SciencesVolume 698, Issue 1 p. 406-417 Cancer Therapy Using Radioimmunoconjugates Implications for Breast Cancer MARGARET TEMPERO, Corresponding Author MARGARET TEMPERO Department of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska 68198-3330Dr. Margaret Tempera, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, Nebraska 68198-3330.Search for more papers by this authorDAVID COLCHER, DAVID COLCHER Departments of Pathology and Microbiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorGLENN DALRYMPLE, GLENN DALRYMPLE Department of Radiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorKATHERINE HARRISON, KATHERINE HARRISON Department of Radiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorKAREN HOLDEMAN, KAREN HOLDEMAN Department of Radiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorSHANTARAM JOSHI, SHANTARAM JOSHI Departments of Cell Biology and Anatomy University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorSYED QUADRI, SYED QUADRI Department of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorJAMES LINDER, JAMES LINDER Departments of Pathology and Microbiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorSAM AUGUSTINE, SAM AUGUSTINE Department of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorELIZABETH REED, ELIZABETH REED Department of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorPETER LEICHNER, PETER LEICHNER Department of Radiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this author MARGARET TEMPERO, Corresponding Author MARGARET TEMPERO Department of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska 68198-3330Dr. Margaret Tempera, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, Nebraska 68198-3330.Search for more papers by this authorDAVID COLCHER, DAVID COLCHER Departments of Pathology and Microbiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorGLENN DALRYMPLE, GLENN DALRYMPLE Department of Radiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorKATHERINE HARRISON, KATHERINE HARRISON Department of Radiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorKAREN HOLDEMAN, KAREN HOLDEMAN Department of Radiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorSHANTARAM JOSHI, SHANTARAM JOSHI Departments of Cell Biology and Anatomy University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorSYED QUADRI, SYED QUADRI Department of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorJAMES LINDER, JAMES LINDER Departments of Pathology and Microbiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorSAM AUGUSTINE, SAM AUGUSTINE Department of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorELIZABETH REED, ELIZABETH REED Department of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this authorPETER LEICHNER, PETER LEICHNER Department of Radiology University of Nebraska Medical Center Omaha, Nebraska 68198-3330Search for more papers by this author First published: November 1993 https://doi.org/10.1111/j.1749-6632.1993.tb17234.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume698, Issue1Breast Cancer: From Biology to Therapy–Pisa Symposia in OncologyNovember 1993Pages 406-417 RelatedInformation

Radioimmunopharmaceutical agents enabling rapid high-reso- lution imaging, high tumor-to-background ratios, and minimal immunogenicity are being sought for cancer diagnosis and im- aging. Genetic engineering techniques have allowed the design of single-chain Fv's (scFv's) of monoclonal antibodies (mAbs) recognizing tumor-associated antigens. These scFv's show good tumor targeting and biodistribution properties in vivo, indicating their potential as imaging agents when labeled with a suitable radionuclide. Methods: Divalent (sc(Fv)2) and tetrava- lent ((sc(Fv)2)2) scFv's of mAb CC49 were evaluated for radio- immunolocalization of LS-174T colon carcinoma xenografts in athymic mice. scFv's were radiolabeled with 99mTc by way of the bifunctional chelator succinimidyl-6-hydrazinonicotinate hydro- chloride using tricine as the transchelator. The immunoreactivity and in vitro stability of the scFv's were analyzed after radiola- beling. Biodistribution and pharmacokinetic studies were per- formed to determine the tumor-targeting potential of the radio- labeled scFv's. Whole-mouse autoradiography illustrated the possible application of these 99mTc-labeled multivalent scFv's for imaging. Results: The radiolabeling procedure gave $95% radiometal incorporation, with a specific activity of .74 MBq/mg scFv. In solid-phase radioimmunoassay, both sc(Fv)2 and (sc(Fv)2)2 exhibited 75%- 85% immunoreactivity, with non- specific binding between 0.8% and 1.2%. Size-exclusion high- performance liquid chromatography showed sc(Fv)2 as a 60- kDa protein and (sc(Fv)2)2 as a 120-kDa protein. Blood clearance studies showed the elimination half-life of 99mTc-labeled sc(Fv)2 as 144 min and that of (sc(Fv)2)2 as 307 min. Whole-body clear- ance studies confirmed the rapid elimination of scFv's, with half-lives of 184 6 19 min for sc(Fv)2 and 265 6 39 min for (sc(Fv)2)2 (P , 0.001). At 6 h after administration, the tumor localization was 7.2 6 0.7 percentage injected dose per gram of tumor (%ID/g) for 99mTc-sc(Fv)2. 99mTc-(sc(Fv)2)2 showed a tumor uptake of 19.1 6 1.1 %ID/g at the same time; the amount of radioactivity in the tumors was 4-fold higher than in the spleen and kidneys and 2-fold higher than in the liver. Macroautora- diography performed at 6 and 16 h after administration clearly detected the tumor with both scFv's. Conclusion: 99mTc- labeled multivalent scFv's show good tumor-targeting charac- teristics and high radiolocalization indices (tumor-to-back- ground ratio). These reagents, therefore, have the potential for use in clinical imaging studies of cancer in the field of nuclear medicine.