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Quantitative ⁸⁹Zr Immuno-PET for In Vivo Scouting of ⁹⁰Y-Labeled Monoclonal Antibodies in Xenograft-Bearing Nude Mice

¹ Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands
² Radionuclide Center, VU University, Amsterdam, The Netherlands
³ PET Center, VU University Medical Center, Amsterdam, The Netherlands
⁴ Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands

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-N-sucDf-⁸⁹Zr. After correction for partial-volume effects, an excellent correlation was found between image-derived ⁸⁹Zr tumor radioactivity and -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.

Key Words: ⁸⁹Zr • PET • monoclonal antibodies • xenograft-bearing nude mice • ⁹⁰Y

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