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

AbstractUNLABELLED:
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 (89)Zr-labeled monoclonal antibodies (mAbs) and (90)Y-mAb RIT might form such a valuable combination. In this study, the biodistribution of (89)Zr-labeled and (88)Y-labeled mAb ((88)Y as substitute for (90)Y) was compared and the quantitative imaging performance of (89)Zr immuno-PET was evaluated.
METHODS:
Chimeric mAb (cmAb) U36, directed against an antigen preferentially expressed in head and neck cancer, was labeled with (89)Zr using the bifunctional chelate N-succinyldesferrioxamine B (N-sucDf) and with (88)Y 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. (89)Zr was evaluated and compared with (18)F 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-(89)Zr was evaluated by relating image-derived tumor uptake data (noninvasive method) to (89)Zr uptake data derived from excised tumors (invasive method).
RESULTS:
(89)Zr-N-sucDf-labeled and (88)Y-p-SCN-Bz-DOTA-labeled cmAb U36 showed a highly similar biodistribution, except for sternum and thigh bone at later time points (72 and 144 h after injection). Small differences were found in kidney and liver. Imaging performance of (89)Zr approximates that of (18)F, whereas millimeter-sized (19-154 mg) tumors were visualized in xenograft-bearing mice after injection of cmAb U36-N-sucDf-(89)Zr. After correction for partial-volume effects, an excellent correlation was found between image-derived (89)Zr tumor radioactivity and gamma-counter (89)Zr values of excised tumors (R(2) = 0.79).
CONCLUSION:
The similar biodistribution and the favorable imaging characteristics make (89)Zr a promising candidate for use as a positron-emitting surrogate for (90)Y.
AuthorsIris 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
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 44 Issue 10 Pg. 1663-70 (Oct 2003) ISSN: 0161-5505 [Print] United States
PMID14530484 (Publication Type: Comparative Study, Evaluation Study, Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Radioisotopes
  • Radiopharmaceuticals
  • Yttrium Radioisotopes
  • Zirconium
Topics
  • Animals
  • Antibodies, Monoclonal (pharmacokinetics)
  • Carcinoma, Squamous Cell (diagnostic imaging, metabolism)
  • Cell Line, Tumor
  • Female
  • Head and Neck Neoplasms (diagnostic imaging, metabolism, radiotherapy)
  • Humans
  • Isotope Labeling (methods)
  • Metabolic Clearance Rate
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Organ Specificity
  • Phantoms, Imaging
  • Radioimmunotherapy (methods)
  • Radioisotopes (pharmacokinetics)
  • Radiopharmaceuticals (pharmacokinetics)
  • Statistics as Topic
  • Tissue Distribution
  • Tomography, Emission-Computed (instrumentation, methods)
  • Transplantation, Heterologous
  • Yttrium Radioisotopes (pharmacokinetics, therapeutic use)
  • Zirconium (pharmacokinetics)

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