title: Pretargeting: taking an alternate route for localizing radionuclides.
abstract: Bispecific antibody pretargeting is a two-step procedure for selectively delivering radionuclides to tumors. The procedure was developed to solve a number of problems encountered when radionuclides are directly coupled to an IgG, such as slow blood clearance and delayed tumor accretion. While various forms of antibody fragments can reduce blood pool activity and provide faster tumor localization, tumor uptake is reduced considerably. In pretargeting procedures, the radionuclide is attached to a small molecule that quickly traverses the vascular barrier to reach the tumor cells, achieving maximum accretion within 0.5 to 1.0 h. Just as quickly, it is eliminated from the body, thereby minimizing tissue exposure and developing high tumor/tissue ratios very early. In order to capture the radionuclide in the tumor, a bispecific antibody (bsMAb) that binds to the tumor and to the isotope carrier (e.g., a hapten-peptide) is pre-administered some time earlier. The pretargeting procedure has been shown repeatedly to improve tumor localization as compared to directly radiolabeled antibodies, thereby enhancing both imaging and therapy. In this article, we review the progress our group has made toward developing and testing bsMAb pretargeting systems for cancer detection and therapy.
authors.affiliation: Garden State Cancer Center at the Center for Molecular Medicine and Immunology, 300 The American Road, Morris Plains, 07950 NJ, USA. rmsharkey@gscancer.org
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Chang
authors.forename: Edmund A
authors.initials: EA
authors.lastname: Rossi
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D016719:Radioimmunodetection; D011868:Radioisotopes / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D011868:Radioisotopes