ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers (diabodies).
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.
Olafsen
Tove
T
Department of Molecular and Medical Pharmacology, UCLA Crump Institute for Molecular Imaging, Los Angeles, CA 90095, USA. tolafsen@mednet.ucla.edu
Sirk
Shannon J
SJ
Betting
David J
DJ
Kenanova
Vania E
VE
Bauer
Karl B
KB
Ladno
Waldemar
W
Raubitschek
Andrew A
AA
Timmerman
John M
JM
Wu
Anna M
AM
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
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D007457:Iodine Radioisotopes; D057127:Single-Chain Antibodies; D000069283:Rituximab