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Radiation Dosimetry of ⁸⁹Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients

¹ Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands; ² Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands; and ³ Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands

Correspondence: For correspondence or reprints contact: Ronald Boellaard, Department of Nuclear Medicine and PET Research, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. E-mail: r.boellaard{at}vumc.nl

Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter ⁸⁹Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans ⁸⁹Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the ⁸⁹Zr-labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. Methods: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of ⁸⁹Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo radioactivity measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. Results: ⁸⁹Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% ± 16.9% [mean ± SD]) except for heavy-weight patients (>100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, –8.4% ± 34.5%). The mean absorbed red marrow dose was 0.07 ± 0.02 mSv/MBq and 0.09 ± 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 ± 0.27 mSv/MBq in men and 1.35 ± 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 ± 0.03 mSv/MBq in men and 0.66 ± 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. Conclusion: ⁸⁹Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.

Key Words: immuno-PET • molecular imaging • head and neck cancer patients • ⁸⁹Zr-labeled monoclonal antibody • dosimetry

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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JNM 2009 50: 11A-12A. [Full Text]