Zirconium-89 for positron emission tomography and hydroxamate resin column for gallium-68 generator

Zirconium-89 (⁸⁹Zr), 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. ⁸⁹Zr can be produced from Yttrium-89 (⁸⁹Y) by a process of cyclotron bombardment with ⁸⁹Y(p, n)⁸⁹Zr reaction. Purification and radiolabelling processes must be developed before ⁸⁹Zr can be used for monoclonal antibody PET imaging. The main aim of this study was to produce ⁸⁹Zr using various types of ⁸⁹Y solid targets through irradiation in a 12 MeV medical cyclotron at low currents using ⁸⁹Y(p, n)⁸⁹Zr reaction for PET imaging in a preclinical condition. Five techniques of ⁸⁹Y solid targets were prepared for the production of ⁸⁹Zr. Gamma spectrum analyses determined energy peaks of 511 keV and 909 keV indicating that ⁸⁹Zr radionuclide had been successfully produced. ⁸⁹Zr 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 ⁸⁹Zr and trastuzumab. PET images at 24 hours showed a selective accumulation of ⁸⁹Zr-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 ⁸⁹Zr. In addition, the capability of the hydroxamate resin column as a new potential column was investigated for ⁶⁸Ga purification and radiolabelling in a ⁶⁸Ga generator. Hydroxamate resin column was used to trap ⁶⁸Ga in alkaline solution and ⁶⁸Ga 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 ⁶⁸Ga 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 ⁶⁸Ga radionuclide. Series elution tests of ⁶⁸Ga 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 ⁶⁸Ga elution and comparable to 0.5 M HCl which is currently being used as ⁶⁸Ga extraction agent from ⁶⁸Ge/⁶⁸Ga generator. Experiments on ⁶⁸Ga radiopharmaceutical radiolabelling reported that ⁶⁸Ga-Df-Trastuzumab radiolabelling was successful according to TLC and HPLC analysis results; however, weak radiolabelling efficiency was found for ⁶⁸Ga-Pentetreotide radiolabelling. In conclusion, ⁸⁹Zr was produced through irradiation at 10 µA using ⁸⁹Y(p, n)⁸⁹Zr 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 ⁶⁸Ga generator was promising, where ⁶⁸Ga 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 ⁶⁸Ga radiopharmaceutical for PET imaging.