Page 28 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer
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                                Chapter 2
Synthesis of 89Zr-cmAb U36
The synthesis and purification of 89Zr, its coupling to cmAb U36 via the chelate Df (Desferal®, Novartis Pharma AG, Basel, Switzerland), as well as the procedures and results of quality tests, have been described previously (2). 89Zr emits positrons with a main energy of 897 keV and an abundance of 22.7%. In addition, non-prompt 909 keV photons are emitted at an abundance of 99.9%.
Pharmacokinetics
Serial blood samples were taken from a peripheral vein of the arm opposite the infusion site for determination of activity at the following time points: 5, 10, and 30 min, and 1, 2, 4, 16, 21, 72, and 168 h after completion of infusion. Urine was collected in intervals 0-24, 24-48, and 48-72 h p.i. to determine renal excretion of 89Zr. Aliquots of blood, plasma, and urine samples were measured for 89Zr activity in an isotope well-counter (1470 Wizard, Wallac, Turku, Finland), compared to an aliquot retained from the conjugate preparation, and corrected for decay. Blood activity was expressed as the percentage of the injected dose per kg (%ID/kg).
PET acquisition
PET scans were obtained at 1 h (all patients, except no 4 and 16), 24 h (patients 1-6), 72 h (all patients) and/or 144 h (all patients, except no 1, 2, and 13) after intravenous injection of 89Zr-cmAb U36, using a dedicated full ring PET scanner (ECAT EXACT HR+, CTI/Siemens, Knoxville, TN, USA) as described before (2). Prior to this study, the PET scanner was calibrated using a standard cylindrical calibration phantom filled with a 5 kBq/cm3 89Zr solution. This calibration was performed to verify the quantitative accuracy of the scanner in the presence of 909 keV gamma photons emitted by 89Zr and the impact of emission spillover into the transmission scans. This procedure indicated that activity concentrations measured with the HR+ were accurate within 5%. During image reconstruction all scans were normalized and corrected for randoms, scatter, attenuation, and decay. Reconstructions were performed using an attenuation and normalization weighted ordered subset expectation maximization (OSEM) algorithm (ECAT software version 7.2, CTI/Siemens) with 2 iterations and 16 subsets followed by post- smoothing of the reconstructed image using a 5-mm FWHM Gaussian filter. Due to the low amount of radioactivity administered to the patients (for radiation exposure reasons), images with attenuation correction showed high noise levels. Therefore, OSEM reconstructions without attenuation (and thus scatter) correction were performed as well and used for visual interpretation only.
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