title: ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers (diabodies).
abstract: Rapid clearing engineered antibody fragments for immunoPET promise high sensitivity at early time points. Here, tumor targeting of anti-CD20 diabodies (scFv dimers) for detection of low-grade B-cell lymphomas were evaluated. In addition, the effect of linker length on oligomerization of the diabody was investigated. Four rituximab scFv variants in the V(L)-V(H) orientation with different linker lengths between the V domains (scFv-1, scFv-3, scFv-5, scFv-8), plus the scFv-5 with a C-terminal cysteine (Cys-Db) for site-specific modification were generated. The scFv-8 and Cys-Db were radioiodinated with (124)I for PET imaging, and biodistribution of (131)I-Cys-Db was carried out at 2, 4 10 and 20 h. The five anti-CD20 scFv variants were expressed as fully functional dimers. Shortening the linker to three or one residue did not produce higher order of multimers. Both (124)I-labeled scFv-8 and Cys-Db exhibited similar tumor targeting at 8 h post injection, with significantly higher uptakes than in control tumors (P < 0.05). At 20 h, less than 1% ID/g of (131)I-labeled Cys-Db was present in tumors and tissues. Specific tumor targeting and high contrast images were achieved with the anti-CD20 diabodies. These agents extend the repertoire of reagents that can potentially be used to improve detection of low-grade lymphomas.
authors.affiliation: Department of Molecular and Medical Pharmacology, UCLA Crump Institute for Molecular Imaging, Los Angeles, CA 90095, USA. tolafsen@mednet.ucla.edu
authors.forename: Tove
authors.initials: T
authors.lastname: Olafsen
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Sirk
authors.forename: David J
authors.initials: DJ
authors.lastname: Betting
authors.forename: Vania E
authors.initials: VE
authors.lastname: Kenanova
authors.forename: Karl B
authors.initials: KB
authors.lastname: Bauer
authors.forename: Waldemar
authors.initials: W
authors.lastname: Ladno
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Raubitschek
authors.forename: John M
authors.initials: JM
authors.lastname: Timmerman
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived; D019281:Dimerization; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology; D007457:Iodine Radioisotopes; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D049268:Positron-Emission Tomography; D000069283:Rituximab; D057127:Single-Chain Antibodies / Q000737:chemistry* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D007457:Iodine Radioisotopes; D057127:Single-Chain Antibodies; D000069283:Rituximab