Zirconium-labeled monoclonal antibodies and their distribution in tumor- bearing nude mice

A method to label monoclonal antibodies (MAbs) with ⁸⁸Zr and ⁸⁹Zr has been developed and tested on the MAbs 323/A3 and E48. Methods: The bifunctional chelating agent desferal (Df) was linked through a thioether bond to the MAbs. Labeling was accomplished by addition of the premodified antibodies to isolated Zr. The retention of the in vivo behavior of the MAbs was determined by comparing the biodistribution of ⁸⁸Zr-labeled MAbs with those of ¹²³I and ^99mTc in mice bearing tumor xenografts. Results: The labeling was simple and the yields were high (above 90%). The obtained conjugates retained their immunoreactivity (>80%). The blood clearance and biodistribution of Zr-labeled MAbs resembled those of the reference conjugates. The Zr-Df-MAb conjugates showed a specific tumor accumulation. Zirconium-89-labeled 323/A3 could be visualized with a PET camera. The absence of large amounts of Zr present in the bone pointed to a good in vivo stability of the Zr-Df-MAb conjugates. Conclusion: This method is well suited for labeling MAbs with Zr isotopes. Using ⁸⁹Zr, the biodistribution of the radioimmunoconjugate can easily be visualized with a PET camera.