Zirconium-labeled monoclonal antibodies and their distribution in tumor-bearing nude mice.
Słowa kluczowe
Abstrakcyjny
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.
CONCLUSIONS
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.
