Radiation Dosimetry of 89Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients
Pontus K.E. Börjesson 1,
Yvonne W.S. Jauw 1,
Remco de Bree 1,
Jan C. Roos 2,
Jonas A. Castelijns 3,
C. René Leemans 1,
Guus A.M.S. van Dongen 4,
and
Ronald Boellaard 2*
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
3 Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands
4 Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands; Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: r.boellaard{at}vumc.nl.
 |
Abstract |
|---|
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
