p-Isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging

Eur J Nucl Med Mol Imaging. 2010 Feb;37(2):250-9. doi: 10.1007/s00259-009-1263-1. Epub 2009 Sep 18.


Purpose: Immuno-PET is an emerging imaging tool for the selection of high potential antibodies (mAbs) for imaging and therapy. The positron emitter zirconium-89 ((89)Zr) has attractive characteristics for immuno-PET with intact mAbs. Previously, we have described a multi-step procedure for stable coupling of (89)Zr to mAbs via the bifunctional chelate (BFC) tetrafluorophenol-N-succinyldesferal (TFP-N-sucDf). To enable widespread use of (89)Zr-immuno-PET, we now introduce the novel BFC p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) and compare its performance in (89)Zr-immuno-PET with the reference BFC TFP-N-sucDf.

Methods: Three mAbs were premodified with Df-Bz-NCS and labeled with (89)Zr at different pHs to assess the reaction kinetics and robustness of the radiolabeling. Stability of both (89)Zr-Df-Bz-NCS- and (89)Zr-N-sucDf-conjugates was evaluated in different buffers and human serum. Comparative biodistribution and PET studies in tumor-bearing mice were undertaken.

Results: The selected conjugation conditions resulted in a chelate:mAb substitution ratio of about 1.5:1. Under optimal radiolabeling conditions (pH between 6.8-7.2), the radiochemical yield was >85% after 60 min incubation at room temperature, resulting in radioimmunoconjugates with preserved integrity and immunoreactivity. The new radioimmunoconjugate was very stable in serum for up to 7 days at 37 degrees C, with <5% (89)Zr release, and was equally stable compared to the reference conjugate when stored in the appropriate buffer at 4 degrees C. In biodistribution and imaging experiments, the novel and the reference radioimmunoconjugates showed high and similar accumulation in tumors in nude mice.

Conclusions: The novel Df-Bz-NCS BFC allows efficient and easy preparation of optimally performing (89)Zr-labeled mAbs, facilitating further exploration of (89)Zr-immuno-PET as an imaging tool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / pharmacokinetics*
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Chelating Agents / chemistry*
  • Deferoxamine / analogs & derivatives*
  • Deferoxamine / chemistry
  • Female
  • Humans
  • Isothiocyanates / chemistry*
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Mice
  • Mice, Nude
  • Organ Specificity
  • Positron-Emission Tomography / methods*
  • Radioimmunodetection / methods
  • Radioisotopes / chemistry
  • Radioisotopes / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution
  • Zirconium / chemistry
  • Zirconium / pharmacokinetics*


  • 4-isothiocyanatobenzyl-desferrioxamine
  • Antibodies, Monoclonal
  • Chelating Agents
  • Isothiocyanates
  • Radioisotopes
  • Radiopharmaceuticals
  • Zirconium
  • Deferoxamine