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Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients.

AbstractUNLABELLED:
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.
AuthorsPontus 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
JournalJournal 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
PMID19837762 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Radioisotopes
  • Recombinant Fusion Proteins
  • Zirconium
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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