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OtherBasic Science Investigations

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

Iris Verel, Gerard W.M. Visser, Ronald Boellaard, Otto C. Boerman, Julliette van Eerd, Gordon B. Snow, Adriaan A. Lammertsma and Guus A.M.S van Dongen
Journal of Nuclear Medicine October 2003, 44 (10) 1663-1670;
Iris Verel
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Gerard W.M. Visser
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Ronald Boellaard
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Otto C. Boerman
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Julliette van Eerd
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Gordon B. Snow
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Adriaan A. Lammertsma
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Guus A.M.S van Dongen
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Abstract

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 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.

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

Footnotes

  • Received Feb. 19, 2003; revision accepted May 22, 2003.

    For correspondence or reprints contact: Guus A.M.S. van Dongen, PhD, Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.

    E-mail: gams.vandongen{at}vumc.nl

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Journal of Nuclear Medicine
Vol. 44, Issue 10
October 1, 2003
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Quantitative 89Zr Immuno-PET for In Vivo Scouting of 90Y-Labeled Monoclonal Antibodies in Xenograft-Bearing Nude Mice
Iris Verel, Gerard W.M. Visser, Ronald Boellaard, Otto C. Boerman, Julliette van Eerd, Gordon B. Snow, Adriaan A. Lammertsma, Guus A.M.S van Dongen
Journal of Nuclear Medicine Oct 2003, 44 (10) 1663-1670;

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Quantitative 89Zr Immuno-PET for In Vivo Scouting of 90Y-Labeled Monoclonal Antibodies in Xenograft-Bearing Nude Mice
Iris Verel, Gerard W.M. Visser, Ronald Boellaard, Otto C. Boerman, Julliette van Eerd, Gordon B. Snow, Adriaan A. Lammertsma, Guus A.M.S van Dongen
Journal of Nuclear Medicine Oct 2003, 44 (10) 1663-1670;
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