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

Kasbollah, A 2013, Zirconium-89 for positron emission tomography and hydroxamate resin column for gallium-68 generator, Doctor of Philosophy (PhD), Medical Sciences, RMIT University.


Document type: Thesis
Collection: Theses

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Title Zirconium-89 for positron emission tomography and hydroxamate resin column for gallium-68 generator
Author(s) Kasbollah, A
Year 2013
Abstract 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.
Degree Doctor of Philosophy (PhD)
Institution RMIT University
School, Department or Centre Medical Sciences
Keyword(s) positron emission tomography (PET)
monoclonal antibodies
yttrium solid target
89Zr radionuclide
radiolabelling
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