Browsing by Author "Le Roux, Johannes Stephanus"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Optimization of production methods for gallium-68 PET radiopharmaceuticals in a hospital radiopharmacy
    (Stellenbosch : Stellenbosch University, 2020-12) Le Roux, Johannes Stephanus; Rubow, Sietske Margarete
    ENGLISH SUMMARY : Production of radiopharmaceuticals intended for human use and research purposes is generally performed in well-equipped commercial or research facilities that usually have access to advanced equipment for the synthesis and quality control of radiopharmaceuticals. Nuclear Medicine departments are in most cases situated in hospitals. Radiopharmacies in these departments usually have limited space and equipment which necessitates careful consideration of suitable production methods. Optimization may include methods to simplify quality control procedures through the use of less sophisticated equipment and procedures. The purpose of this study was to demonstrate how to optimize production methods in an environment with limited resources using ubiquicidin labelled with gallium-68 as an example. The peptide ubiquicidin is currently investigated for localization of infections in patients using positron emission tomography (PET). Until recently, labelling ubiquicidin with gallium-68 was limited to a manual labelling method. Manual labelling methods are not recommended for the routine production of radiopharmaceuticals because of difficulty to comply with Good Manufacturing Practice (GMP). Manual labelling methods can also result in high radiation exposure to personnel. These disadvantages can be addressed by automation of production methods. The research conducted in this study shortly entails the following aspects: •Automation of a manual labelling method of ubiquicidin with gallium-68 •Optimization of the synthesis methods using radical scavengers •In-depth comparison of the labelling characteristics of the manual method to that of theautomated methods •Conducting a literature search into the toxicity of HEPES in humans and animals in order toclarify its use as a buffering agent in the labelling of radiopharmaceuticals • Investigating thin-layer chromatography as method to determine the radiochemical purity of gallium-68 ubiquicidin Two different automated synthesis methods were developed in this study. Optimization of the labelling methods was achieved by adding free-radical scavengers to reduce the formation of impurities. A comparison of the labelling characteristics of the manual labelling method with the automated methods showed that the results obtained with automated methods were more robust and repeatable. The literature search into the toxicity of HEPES showed that its toxicity in humans and animals may be overestimated by pharmacopoeias. The current limits applied by pharmacopoeias may be too strict. An evaluation of several thin-layer chromatography methods indicated that the method currently described in the literature may underestimate the presence of colloidal impurities in the final product. None of the other methods investigated in this study could distinguish the colloidal impurity from the labelled product. This aspect highlights the need for a final purification step to reduce the presence of colloidal impurities in the final product. The work presented in this study creates an important basis for optimization of production methods in a clinical environment. The study can further serve as a guideline to other nuclear medicine departments for optimization of radiopharmaceutical production methods.