Abstract
1058
Purpose: Zirconium-89(89Zr, T1/2 = 3.27 days) is an ideal nuclide for immuno-PET because of its favorite longer half-life and positron-emitted characteristic. Monte Carlo (MC) method provides a convenience method for optimize the nuclides production. This aim of the work is to develop standardized optimized methods for production and purification of next-generation positron radionuclide 89Zr by MC simulation and laboratory experiments. In addition, specific probe named 89Zr-trastuzumab is prepared and micro-PET/CT imaging of mice HER2-positive breast cancers is performed.
Methods: Nuclear reaction 89Y(p,n)89Zr was used for 89Zr production. The widely used FLUKA Monte Carlo method was utilized to simulate the particles transmission in the solid target for irradiation parameters optimization. Simulations were performed with different thickness of Aluminum (Al) degrader and Yttrium (89Y) foil to get the optimal thickness. The Al backing for holding the 89Y target was designed and processed. The 89Y target was then irradiated by 20 μA proton at about 12.5 MeV in a medical cyclotron for about 1~2 hours. After the bombardment, the radioactive target was collected by an automatic device and placed to decay for 24 hours, to allow short-lived radioactive co-product, such as 99mY to decay. Then the target material 89Y/89Zr was dissolved in 6 M hydrochloric acid (HCl) solution. The fully dissolved solution passed through a pre-conditioning hydroxamate resin which was rinsed and actived by 1M oxalate acid, 18 MΩ water (H2O) and 2 M HCl. Then, 89Zr of high radiochemical purity could obtain in 89Zr-oxalate form eluted from the resin by 1 M oxalic acid solution. The radionuclide identity and purity of the produced 89Zr were determined by γ-ray spectroscopy. 89Zr-DFO-trastuzumab probe was labeled by reaction of 89Zr-oxalate and DFO-trastuzumab in HEPES buffer (pH 7.0) for 60 min at room temperature. Micro-PET/CT imaging of mice HER2-positive breast cancers injected 89Zr-DFO-trastuzumab was performed.
Results: The optimal thickness of Al degrader and 89Y foil were 0.1 cm and 0.05~0.07cm. The 89Y foil adhered to the Al backing very well, with smooth surface, weighing about 295 ± 5.8 mg. After irradiation, there were 644 ~ 846 MBq/h (end of the bombarded, EOB) 89Zr produced and 280~734 MBq/h after purification (42%-87% purification yield). The gamma spectrum of the purified 89Zr solution showed no radiochemical impurity, 511 and 909 KeV of inherent gamma energies of Zr-89 clearly found. 89Zr-DFO-trastuzumab was successfully labeled and the radio-TLC confirmed the 89Zr-DFO-trastuzumab solution showed good radiochemical purity (>95%). Micro-PET/CT imaging of 89Zr-DFO-trastuzumab in HER2-positive breast cancers mice showed the good uptake in tumor accumulations at different times post-injection of the radiotracer.
Conclusions: We have successfully produced the next-generation PET nuclide 89Zr guided by MC simulation in sufficient and high quality. The successfully labeling of 89Zr-DFO-trastuzumab probe and HER2-positive breast cancers mice micro-PET/CT imaging show the potential applications of 89Zr-labedled antibodies in immuno-PET imaging for tumor diagnosis and therapy.Keywords: Solid target; Zr-89; Positron emission tomography (PET); Antibody; Immuno-PET; next generation radionuclide
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