Doctoral Degrees (Nuclear Medicine)

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Browsing Doctoral Degrees (Nuclear Medicine) by Subject "Radiolabeling"

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    Investigation into various aspects of radiolabelling somatostatin peptide derivatives with 68Ga eluted from a SnO2-based 68Ge/68Ga generator
    (Stellenbosch : Stellenbosch University, 2018-03) Prince, Deidre Mabel; Rubow, Sietske Margarete; Rossouw, Daniel Dutoit; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
    ENGLISH SUMMARY : 68Ge/68Ga generators ensure the supply of 68Ga for positron emission tomography (PET), for instance for somatostatin receptor imaging with 68Ga-DOTA-labelled somatostatin analogues. There are various generators available and their eluates are processed differently for radiolabelling of peptides. The objectives of this study were to investigate various aspects of the elution characteristics of the generator, to optimize labelling conditions using different eluate processing techniques such as fractionation and cation exchange chromatography and to develop user-friendly kit formulations. This study was approved by the Stellenbosch University Health Research Ethics Committee and permission was granted for the experimental work to be conducted at iThemba LABS. Elution efficiencies were determined using different HCl concentrations (0.2 M – 1.0 M). Metal analysis and 68Ge breakthrough determination were performed on eluates. Radiolabelling parameters were optimized, using fractionated eluates and different DOTA-peptide masses (15 to 50 μg) at pH 3.5 – 4.0 in sodium acetate buffer. Different heating times and heating methods and the influence of various periods of non-elution of the generator on radiolabelling results were investigated. Cationic resins were investigated for eluate processing. Radiolabelling parameters, using cationic resin-processed eluates, were optimized. Labelling was conducted at various pH values, using different quantities of buffer. DOTA-peptide kits for both fractionated and resin-processed eluates were developed and tested for sterility, endotoxin content and stability. Radiochemical yields, radiolabelling efficiency and radiochemical purity of 68Ga-DOTA-peptides were determined. The elution efficiency of the generator increased with an increase in the concentration of HCl eluent. The 68Ge breakthrough increased dramatically at 0.8 M HCl. Most metal contaminants were lowest when eluting with 0.2 M HCl and the Zn content increased with the increase in HCl concentration. The eluent of choice for the SnO2-based generator was confirmed to be 0.6 M HCl. For radiolabelling, 35 μg DOTA-peptide (9.2 – 9.4 μM) was the most favourable. Extended heating times and heating method did not significantly impact on the radiolabelling. The radiolabelling efficiencies were consistently above 90 % even after 3 weeks of non-elution of the generator, but radiochemical yields dropped after 7 days. DOTA-peptide kits for fractionated eluates were successfully developed and the radiolabelling quality was found to be superior over peptide stock solutions. A radiolabelling method using a cationic exchange resin was successfully adapted for the SnO2 generator. 68Ga was efficiently adsorbed on a Bond Elut SCX (100 mg) cartridge and desorbed by acidified solutions of NaCl. The SCX resin effectively removed about 98 % of deliberately “spiked” metals from the 68Ga eluate. An optimized labelling method based on the use of SCX-purified eluates was developed, producing radiochemical yields of almost 85 % and lead to the successful formulation of DOTATATE kits. The quality was found to be suitable over a 3-month period. In conclusion, a kit type labelling procedure, using cationic resin purified 68Ga eluates, provides the most practical method to produce 68Ga-labelled DOTA-peptides.