Quantitative 89Zr immuno-PET for in vivo scouting of 90Y-labeled monoclonal antibodies in xenograft-bearing nude mice

Immuno-PET as a scouting procedure before radioimmunotherapy (RIT) aims at the confirmation of tumor targeting and the accurate estimation of radiation dose delivery to both tumor and normal tissues. Immuno-PET with 89Zr-labeled monoclonal antibodies (mAbs) and 90Y-mAb RIT might form such a valuable combination. In this study, the biodistribution of 89Zr-labeled and 88Y-labeled mAb (88Y as substitute for 90Y) was compared and the quantitative imaging performance of 89Zr immuno-PET was evaluated. Methods: Chimeric mAb (cmAb) U36, directed against an antigen preferentially expressed in head and neck cancer, was labeled with 89Zr using the bifunctional chelate N-succinyldesferrioxamine B (N-sucDf) and with 88Y using the bifunctional chelate p-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4, 7,10-tetraacetic acid (p-SCN-Bz-DOTA). The radioimmunoconjugates were coinjected in xenograft-bearing nude mice, and biodistribution was determined at 3, 24, 48, 72, and 144 h after injection. 89Zr was evaluated and compared with 18F in phantom studies to determine linearity, resolution, and recovery coefficients, using a high-resolution research tomograph PET scanner. The potential of PET to quantify cmAb U36-N-sucDf-89Zr was evaluated by relating image-derived tumor uptake data (noninvasive method) to 89Zr uptake data derived from excised tumors (invasive method). Results: 89Zr-N-sucDf-labeled and 88Y-p-SCN-Bz-DOTA- labeled cmAb U36 showed a highly similar biodistribution, except for sternum and thighbone at later time points (72 and 144 h after injection). Small differences were found in kidney and liver. Imaging performance of 89Zr approximates that of 18F, whereas millimeter-sized (19-154 mg) tumors were visualized in xenograft-bearing mice after injection of cmAb U36-W-sucDf-89Zr. After correction for partial-volume effects, an excellent correlation was found between image-derived 89Zr tumor radioactivity and γ-counter 89Zr values of excised tumors (R2 = 0.79). Conclusion: The similar biodistribution and the favorable imaging characteristics make 89Zr a promising candidate for use as a positron-emitting surrogate for 90Y