Abstract:
Nuclear Medicine imaging involves the monitoring of disease processes by using radioactive signals produced by radiopharmaceuticals (injected intravenously) to monitor the pharmacokinetic behaviour of compounds non-invasively in the human body by special cameras. The most common imaging technique using radioactivity is Positron Emission Tomography (PET). The radiopharmaceuticals are compounds made of two main components, firstly the radionuclide which provides a signal for detection and secondly, a molecular vehicle which is responsible for biochemical functions, binding, metabolism, and clearance. If the radiopharmaceutical is peptide based, these two structural components are made to exist as functional units and their performance is enabled, enhanced, and controlled through the use of different chelators, spacers, and modifications. Receptor expressing tissues will be targeted with these receptor binding peptides and are used for imaging in different applications, for example in specific targeting of tumors.
This thesis highlights the importance of validation of analytical methods in Quality control according to Good Manufacturing Practices, current Good Radiopharmacy Practice and Good Laboratory Practices with a specific application in the field of Radiochemistry and Radiopharmaceutical development. It is important to include these aspects in the design process, as early as the stage of product conception. The aim was to evaluate the gallium-68 radiopharmaceutical development pipeline and provide constructive guidance on best practices. The development of ubiquicidin-derived radiopharmaceuticals, as an exemplary application, was critically investigated using a systematic reviewing strategy (Chapter 4). It was found that the systematization and unification of criteria for preclinical imaging and larger clinical trials are still required to ensure the translation of this new radiopharmaceutical into the clinic. It was observed that there was not enough testing done across different sizes of animals, preventing better and easier translation to humans.
Kits are gaining popularity as a known convenient labelling procedure for gallium-68 based radiopharmaceuticals in the Nuclear Medicine clinic. Cold kits are a benefit to small radiopharmaceutical sites, but their quality should be checked in the same way as if they were produced by big pharmaceutical producers. The purpose of this thesis was to describe analytical methods and step-by-step validation thereof, (according to European Pharmacopoeia requirements) using readily available instrumentation in laboratories.
The validation of the analytical methods that can be used during cold kit production of different gallium-68 radiopharmaceuticals is described in Chapter 3. Validated methods were applied to the PSMA-11 kit as an example and it was found that this product complied with all set requirements.
