M'SONE MSc Abstract - 2011
Supervisor : Dr F de Beer : NECSA and Prof (To be Announced) : UJ
Dr F de Beer, is NECSA's chief scientist on neutron radiography/tomography and current President of the ISNR
Developing New Applications and Products for Radionuclides
This project is based on the two proposals below, but the new proposals aill be modified for MSc level study
Tc-99m ECDG (The write-up below is for a PhD project)
The use of F-18 FDG for general oncology screening is now well established in SA but costs ~R3000 per patient for the radiopharmaceutical. This can be paid by private patients but not by a state hospital without heavy subsidies. This has the consequence that the larger public does not have access to oncology screening. Tc-99m based radiopharmaceuticals are generally between one fifth and one tenth of the price of F-18 FDG. ECDG is a ligand that has potential to be specific for cancerous tissue. This has been well documented in publications and patents. The ligand has recently been successfully manufactured in SA and has now to be labelled with Tc- 99m. The infrastructure to do the labelling as well as prepare formulations for clinical trials in a sterile room is available at Necsa. This project requires a pharmacy or medical student with an MSc to further the synthesis, develop labelling protocols, develop a kit formulation and appropriate quality control measures, and to pursue the necessary animal and human clinical trial tests on this compound. The latter involves the set-up of the required SOPís (Standard Operating Procedures) and GMP related documents required by the MCC for approval for human use.
C-14 and H-3 labelling Ė synthesis (The write-up below is for a Post Doctoral project)
At a recent NTeMBI workshop on labelling of natural compounds the importance and amount of this research area in SA was again emphasised. These compounds are often mixtures but in some instances progress has been made to isolate the active compound. For instance, the natural product aspalathin, isolated from the leaves of Aspalathus linearis and used in the manufacture of rooibos tea, displays potent antioxidant and radical scavenging activity. Its eight step synthesis has recently been published; however its mechanism of action and biodistribution is still unknown, as is the case for many of these compounds isolated from biomaterial. The use of the radiolabels C-14 and H-3 could be helpful to address these questions. In the past, this was also carried out, but due to the sub-optimal detection limits using liquid scintillation counting, in vivo studies required a high amount of radiolabelled compound making it not desirable. However, recent technology improvements with AMS (Accelerator Mass Spetrometer) have lowered the detection levels by orders of magnitude, which imply that the levels of C-14 and H-3 that are required for in vivo studies are much lower. The amounts of radioactivity now required are so low that they are no longer classified as radioactive studies and the regulatory burden of conducting these studies is removed. The dose levels are so low (typically 100 micrograms or less) that there is no need to conduct a preclinical safety package for the intravenous administration. Page 2 In SA iThemba LABS (Gauteng) is currently setting up an AMS which means that this approach will be possible in the near future and therefore NTeMBI has integrated all the role players for the radiolabelling of natural compounds. The C-14 and H-3 labelled compounds however still need to be synthesised. This specific labelling skill does not exist at Necsa and currently not in the rest of the country either. The lab infrastructure at Necsa does exist in the form of the Beta lab. The intention of this project is to re-establish this skill in the country by having an Organic chemist specialising in this direction for his post-doctoral studies and at the same time develop human capacity to support this area in the future.