Abstract | UNLABELLED: 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 (89)Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans (89)Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the (89)Zr-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 (89)Zr-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: (89)Zr-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: (89)Zr 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.
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Authors | Pontus K E Börjesson, Yvonne W S Jauw, Remco de Bree, Jan C Roos, Jonas A Castelijns, C René Leemans, Guus A M S van Dongen, Ronald Boellaard |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 50
Issue 11
Pg. 1828-36
(Nov 2009)
ISSN: 1535-5667 [Electronic] United States |
PMID | 19837762
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Radioisotopes
- Recombinant Fusion Proteins
- Zirconium
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Topics |
- Aged
- Antibodies, Monoclonal
(adverse effects, chemistry, pharmacokinetics)
- Bone Marrow
(radiation effects)
- Carcinoma, Squamous Cell
(diagnostic imaging, immunology, metabolism)
- Clinical Trials as Topic
- Drug-Related Side Effects and Adverse Reactions
- Female
- Head and Neck Neoplasms
(diagnostic imaging, immunology, metabolism)
- Humans
- Isotope Labeling
- Male
- Middle Aged
- Positron-Emission Tomography
- Radiation Dosage
- Radioisotopes
- Radiometry
- Recombinant Fusion Proteins
(adverse effects, chemistry, pharmacokinetics)
- Tissue Distribution
- Zirconium
(chemistry)
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