Page 24 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer
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                                Chapter 2
ABSTRACT
Immuno-PET is an appealing concept in tumor detection and planning of antibody-based therapy. For this purpose, the long-lived positron emitter zirconium-89 (t1⁄2 = 78.4 h) became recently available. The aim of the present first- in-man 89Zr-immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of 89Zr-labeled-chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously (1).
Methods: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq 89Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, and/or 144 h p.i. Biodistribution of the radioimmunoconjugate was evaluated by ex vivo radioactivity measurement in blood and in biopsies from the surgical specimen obtained 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. 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 (mean deviation, 0.2 ± 16.9 %), except for heavy weight patients (> 100 kg). A good agreement was also found for assessment of mAb uptake in primary tumors (mean deviation, -8.4 ± 34.5 %). The mean absorbed red marrow dose was 0.07 ± 0.02 and 0.09 ± 0.01 mSv/MBq in males and females, respectively. The normal organ with the highest absorbed dose was the liver (mean dose of 1.25 ± 0.27 in males and 1.35 ± 0.21 mSv/MBq in females), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 ± 0.03 mSv/MBq in males and 0.66 ± 0.03 mSv/MBq in females. Measured excretion via the urinary tract was < 3% during the first 72h.
Conclusion: 89Zr-immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose. This justifies its further clinical exploitation in tumor detection and planning of mAb-based therapy.
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