Abstract | UNLABELLED: 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.
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Authors | 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 | Journal 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 |
PMID | 14530484
(Publication Type: Comparative Study, Evaluation Study, Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Radioisotopes
- Radiopharmaceuticals
- Yttrium Radioisotopes
- Zirconium
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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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