Quantitative Zr-89 immuno-PET for in vivo scouting of Y-90-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 Zr-89-labeled monoclonal antibodies (mAbs) and Y-90-mAb RIT might form such a valuable combination. In this study, the biodistribution of Zr-89-labeled and Y-88-labeled mAb (Y-88 as substitute for Y-90) was compared and the quantitative imaging performance of Zr-89 immuno-PET was evaluated. Methods: Chimeric mAb (cmAb) U36, directed against an antigen preferentially expressed in head and neck cancer, was labeled with Zr-89 using the bifunctional chelate N-succinyldesferrioxamine B (N-sucDf) and with Y-88 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. Zr-89 was evaluated and compared with F-18 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-Zr-89 was evaluated by relating image-derived tumor uptake data (noninvasive method) to Zr-89 uptake data derived from excised tumors (invasive method). Results: Zr-89-N-sucDf-labeled and Y-88-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 Zr-89 approximates that of F-18, whereas millimeter-sized (19-154 mg) tumors were visualized in xenograft-bearing mice after injection of cmAb U36-N-sucDf-Zr-89. After correction for partial-volume effects, an excellent correlation was found between image-derived Zr-89 tumor radioactivity and gamma-counter Zr-89 values of excised tumors (R-2 = 0.79). Conclusion: The similar biodistribution and the favorable imaging characteristics make Zr-89 a promising candidate for use as a positron-emitting surrogate for Y-90.