title: Adding a clearing agent to pretargeting does not lower the tumor accumulation of the effector as predicted.
abstract: Clearing agents are often used in pretargeting despite the potential for decreased tumor accumulation of the effector. However, according to the authors' semiempirical model, a clearing agent should not necessarily decrease tumor accumulation. In this study, the authors have added a clearing step to their model-morpholino phosphorodiamidate oligomer (MORF)/complement MORF (cMORF) pretargeting system-to confirm this prediction. The CC49 antibody was conjugated with both biotin and an 18 mer MORF. The influence of avidin on antibody clearance was first evaluated in normal mice in which each animal received 30 μg of MORF-CC49-biotin, 0-70 μg of avidin 1 day later, and 1.2 μg of ⁹⁹(m)Tc-cMORF 3 hours later, with sacrifice at 3 hours. Thereafter, a pretargeting study in mice bearing an LS174T tumor was performed at a 34 μg avidin dosage. In normal mice, the blood level of ⁹⁹(m)Tc-cMORF fell by 60% at an avidin dosage of 10 μg or higher. In tumored mice, avidin produced a similar reduction in blood but had no influence on tumor level, which remained at 6.30% ID/g as predicted. In conclusion, in addition to the expected reduced effector levels in blood and normal tissues, a reduction in tumor accumulation was avoided when adding a clearing agent as predicted.
authors.affiliation: Department of Radiology, University of Massachusetts Medical School, Worcester, 01655-0243, USA. guozheng.liu@umassmed.edu
authors.forename: Guozheng
authors.initials: G
authors.lastname: Liu
authors.forename: Shuping
authors.initials: S
authors.lastname: Dou
authors.forename: Xiangji
authors.initials: X
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Xinrong
authors.initials: X
authors.lastname: Liu
authors.forename: Mary
authors.initials: M
authors.lastname: Rusckowski
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hnatowich
mesh_terms: D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D001360:Avidin / Q000494:pharmacology; D001710:Biotin / Q000737:chemistry; D045744:Cell Line, Tumor; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009025:Morpholines / Q000737:chemistry / Q000493:pharmacokinetics*; D060172:Morpholinos; D009369:Neoplasms / Q000378:metabolism*; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C091202:B72.3 antibody; D006023:Glycoproteins; D018796:Immunoconjugates; D009025:Morpholines; D060172:Morpholinos; C047052:tumor-associated antigen 72; D001360:Avidin; D001710:Biotin; D013667:Technetium