Zirconium-89 for positron emission tomography and hydroxamate resin column for gallium-68 generator
Creators: name: Kasbollah, Azahari
Publisher: name: RMIT University
Year: 2024

description: Zirconium-89 (<sup>89</sup>Zr), a radionuclide with a half-life of 78.4 hours, is suitable for imaging tumours using positron emission tomography (PET) when labelled with monoclonal antibodies. <sup>89</sup>Zr can be produced from Yttrium-89 (<sup>89</sup>Y) by a process of cyclotron bombardment with <sup>89</sup>Y(p, n)<sup>89</sup>Zr reaction. Purification and radiolabelling processes must be developed before <sup>89</sup>Zr can be used for monoclonal antibody PET imaging. The main aim of this study was to produce <sup>89</sup>Zr using various types of <sup>89</sup>Y solid targets through irradiation in a 12 MeV medical cyclotron at low currents using <sup>89</sup>Y(p, n)<sup>89</sup>Zr reaction for PET imaging in a preclinical condition. Five techniques of <sup>89</sup>Y solid targets were prepared for the production of <sup>89</sup>Zr. Gamma spectrum analyses determined energy peaks of 511 keV and 909 keV indicating that <sup>89</sup>Zr radionuclide had been successfully produced. <sup>89</sup>Zr was purified through a hydroxamate resin column and radiolabelled to a monoclonal antibody (trastuzumab). Experiments on biodistribution together with PET imaging of female balb/c nude mice having the HER2 positive LS174T colorectal tumour were undertaken to validate the successful radiolabelling procedure between <sup>89</sup>Zr and trastuzumab. PET images at 24 hours showed a selective accumulation of <sup>89</sup>Zr-Df-Trastuzumab in tumour-bearing mice with good tumour tracer uptake in the right flank, as well as cardiac uptake, a significant presence of HER2 receptor expression on the heart, demonstrated that the conjugated Df-Trastuzumab was successfully labelled with <sup>89</sup>Zr. In addition, the capability of the hydroxamate resin column as a new potential column was investigated for <sup>68</sup>Ga purification and radiolabelling in a <sup>68</sup>Ga generator. Hydroxamate resin column was used to trap <sup>68</sup>Ga in alkaline solution and <sup>68</sup>Ga was purified and eluted from hydroxamate resin column using citrate buffer at pH 4 as an extraction agent. It was then labelled to a monoclonal antibody to produce <sup>68</sup>Ga radiopharmaceutical for PET imaging. The first series of experiments on different quantities of hydroxamate resin column indicated that 50 mg of the resin was suitable for the optimum extraction of <sup>68</sup>Ga radionuclide. Series elution tests of <sup>68</sup>Ga from the hydroxamate resin column using various buffers including acetate, citrate and citrate in hydrochloric acid (HCl) with different concentrations were performed. The results indicated that 0.1 M citrate buffer was suitable for <sup>68</sup>Ga elution and comparable to 0.5 M HCl which is currently being used as <sup>68</sup>Ga extraction agent from <sup>68</sup>Ge/<sup>68</sup>Ga generator. Experiments on <sup>68</sup>Ga radiopharmaceutical radiolabelling reported that <sup>68</sup>Ga-Df-Trastuzumab radiolabelling was successful according to TLC and HPLC analysis results; however, weak radiolabelling efficiency was found for <sup>68</sup>Ga-Pentetreotide radiolabelling. In conclusion, <sup>89</sup>Zr was produced through irradiation at 10 µA using <sup>89</sup>Y(p, n)<sup>89</sup>Zr reaction in a 12 MeV medical cyclotron and was successfully radiolabelled to trastuzumab for PET imaging in a preclinical condition. In addition, the potential of hydroxamate resin to be used as a new column in a <sup>68</sup>Ga generator was promising, where <sup>68</sup>Ga was purified and eluted from a hydroxamate resin column using 0.1 M citrate buffer at pH 4 as an extraction agent. It was successfully labelled to a monoclonal antibody to produce <sup>68</sup>Ga radiopharmaceutical for PET imaging.