Radioimaging

Overview

Positron emission tomography can be used to visualize antibodies and other biologics non-invasively, in vivo. Revvity offers Zirconium-89 (Zr-89)* radionuclide for labeling biologics for use in in vivo imaging research. Zr-89 is offered for molecular imaging using immuno-positron emission tomography (immuno-PET) or Cerenkov luminescence imaging (CLI) techniques. Zr-89 is a long-living positron emitter, providing an advantage over other emitters such as ¹⁸F and ⁸⁶Y when labeling large biomolecules (including therapeutic monoclonal antibodies) that accumulate more-slowly in vivo. Immuno-PET with Zr-89 radionuclide enables noninvasive imaging of whole, intact antibodies.

*Available outside US only

Products and catalog numbers

For immuno-PET research applications, Zr-89 is commonly used for internalizing monoclonal antibodies because it is trapped inside the cell after internalization of the antibody (residualization). ⁸⁹Zr has a relatively long half-life (beyond that of 18F, Gallium-68, ⁶⁴Cu, or ⁸⁶Y), enabling imaging at later timepoints needed for larger research biologics.

Labeling antibodies with Zr-89

Antibodies are typically labeled indirectly with Zr-89 using a chelator, though direct labeling approaches have been described for labeling other biomolecules with Zr-89. The most common method for labeling is using Desferrioxamine B  (DFO). DFO is available as a salt, or in reactive forms such as isothiocyanate (ITC; labels lysine residues), maleimide (labels thiol groups/cysteine residues), and tetrafluorophenolic ester/Fe³⁺ derivatives (labels lysine residues).

FAQs

Q. Is Desferal (Df) the only suitable chelator for stable incorporation of Zr-89? 
A. Yes, DOTA, NOTA or DTPA are not suitable for stable incorporation of Zr-89.

Q. Which Df chelator is best option for my research? 
A. This depends on the type of research. The TFP-nSuc-Df chelator has been used safely for many years and is commercially available at ABX (www.ABX.com), but requires the extra Fe-removal step at pH 4. The Df-Bz-NCS chelator was recently introduced in the clinic and is commercially available at Macrocyclics. Both of these are suitable for use in research applications.

Q. What are the minimum quantities of mAb to obtain reliable labelling yields? 
A. For Zr-89 we prefer to start the conjugation of the Df-chelator to the antibody with at least 2 mg mAb, and then subsequently radiolabel at least 0.5 mg mAb-Df.

Citations

1. Fischer, G., Seibold, U., Schirrmacher, R., Wängler, B. & Wängler, C. (89)Zr, a radiometal nuclide with high potential for molecular imaging with PET: chemistry, applications and remaining challenges. Molecules18, 6469–6490 (2013).  Link
2. Treglia, G. & Salsano, M. PET imaging using radiolabelled antibodies: future direction in tumor diagnosis and correlate applications. Research and Reports in Nuclear Medicine 9 (2013).
3. Verel, I. et al. Long-lived positron emitters zirconium-89 and iodine-124 for scouting of therapeutic radioimmunoconjugates with PET. Cancer Biother. Radiopharm.18, 655–661 (2003).  Link
4. Wu, A. M. & Olafsen, T. Antibodies for molecular imaging of cancer. Cancer J14, 191–197 (2008).  Link

For research use only. Not for use in diagnostic procedures.

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