The chemical synthesis, pharmaceutical preparation and toxicity analysis of fluorodopa for positron emission tomography (PET) brain imaging in South Africa

Abstract

Parkinson’s disease (PD) impairs the quality of life of patients and causes substantial social and economic burden. However the currently available symptomatic treatments, although initially effective, do not satisfactorily control the progressive disability experienced by patients with PD in the long run. In order to develop effective treatments for patients that aim to attain the desired effect with as few adverse events as possible, it is crucial to be able to follow and understand the biological mechanisms underlying the continued neural degeneration and treatment failure. The efforts to understand the precise pathway by which neurodegenerative processes proceed and the development of approaches to modulate them offers the promise to eventually enable the prevention of these neurodegenerative diseases. This dissertation focused on two potential synthetic methods to produce pharmaceutical grade Fluorodopa, ultimately to be able to produce positron emitting 18Fluorodopa in South Africa with its potential for studying neuronal mechanisms in the brain. 18Fluorodopa allows a unique almost non-invasive in vivo approach to the evaluation of neurochemical function in the human brain and its local introduction will be a valuable addition to medical research within South Africa’s borders. The successful implementation of safe and efficient non-radioactive models for Fluorodopa synthesis was achieved. The successful demonstration of locally synthesised Fluorodopa safety, as well as a low toxicity profile, both in vitro using cell cultures and in vivo in mouse models was achieved. These were both positive outcomes of objectives set out for this study. Copyright