Journal Article

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

Jauw, Yvonne W.S, Boellaard, Ronald, van Dongen, Guus A.M.S, Leemans, C. Rene, de Bree, Remco, Borjesson, Pontus K.E, Castelijns, Jonas A, Roos, Jan C

2009

Overview

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. 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. (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. (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.

• Publisher: Soc Nuclear Med
• Subject: Aged / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - chemistry / Antibodies, Monoclonal - pharmacokinetics / Bone Marrow - radiation effects / Carcinoma, Squamous Cell - diagnostic imaging / Carcinoma, Squamous Cell - immunology / Carcinoma, Squamous Cell - metabolism / Clinical Trials as Topic / Drug-Related Side Effects and Adverse Reactions / Female / Head and Neck Neoplasms - diagnostic imaging / Head and Neck Neoplasms - immunology / Head and Neck Neoplasms - metabolism / Humans / Isotope Labeling / Male / Middle Aged / Positron-Emission Tomography / Radiation Dosage / Radioisotopes / Radiometry / Recombinant Fusion Proteins - adverse effects / Recombinant Fusion Proteins - chemistry / Recombinant Fusion Proteins - pharmacokinetics / Tissue Distribution / Zirconium - chemistry