ZIRCONIUM-LABELED MONOCLONAL-ANTIBODIES AND THEIR DISTRIBUTION IN TUMOR-BEARING NUDE-MICE

A method to label monoclonal antibodies (MAbs) with Zr-88 and Zr-89 ha s been developed and tested on the MAbs 323/A3 and E48. Methods: The b ifunctional chelating agent desferal (Df) was linked through a thioeth er bond to the Mabs. Labeling was accomplished by addition of the prem odified antibodies to isolated Zr. The retention of the in vivo behavi or of the MAbs was determined by comparing the biodistribution of Zr-8 8-labeled MAbs with those of I-123 and Tc-99m in mice bearing tumor xe nografts. Results: The labeling was simple and the yields were high (a bove 90%). The obtained conjugates retained their immunoreactivity (>8 0). The blood clearance and biodistribution of Zr-labeled MAbs resembl ed those of the reference conjugates. The Zr-Df-MAb conjugates showed a specific tumor accumulation. Zirconium-89-labeled 323/A3 could be vi sualized with a PET camera. The absence of large amounts of Zr present in the bane pointed to a good in vivo stability of the Zr-Df-MAb conj ugates. Conclusion: This method is well suited for labeling MAbs with Zr isotopes. Using Zr-89, the biodistribution of the radioimmunoconjug ate can easily be visualized with a PET camera.