ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers (diabodies)

Protein Eng Des Sel. 2010 Apr;23(4):243-9. doi: 10.1093/protein/gzp081. Epub 2010 Jan 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Murine-Derived
  • Dimerization
  • Female
  • Humans
  • Immunologic Factors / chemistry
  • Immunologic Factors / immunology
  • Iodine Radioisotopes
  • Lymphoma, B-Cell / diagnostic imaging*
  • Lymphoma, B-Cell / immunology
  • Mice
  • Mice, Inbred Strains
  • Positron-Emission Tomography*
  • Rituximab
  • Single-Chain Antibodies / chemistry*
  • Single-Chain Antibodies / immunology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunologic Factors
  • Iodine Radioisotopes
  • Single-Chain Antibodies
  • Rituximab