Synthesis and evaluation of [18F]fluoroprogestins and [18F]fluorometoprolol

The author investigated if specific radioactively labelled compounds could be applied to gain insight into particular psychic diseases, f.e. Parkinson's disease and schizophrenia, by means of Positron Emission Tomography (PET). No appropriate compounds were found. In this thesis the syntheses of fluorine-18 labelled progestins and β1-adrenergic ligands are described. Three approaches towards [18F]fluorination are investigated. The first method concerns direct SN2-substitution, the second approach is the opening of an epoxide, and the third approach is [18F]fluoroalkylation. The positron emitting radionuclide fluorine-18 was used because of its relatively long decay time and the possibility to produce it in high yields and with high specific activity. The target systems which were applied for the production of fluorine-18 are described in chapter two. Important chemical and physical aspects of [18F]fluoride are reviewed in the same chapter. In chapter three the synthesis of 21-[18F]fluorinated progestins is discussed. The synthesis of four 21-[18F]fluoroprogesterone derivatives is described and the results of an in vivo evaluation of two of these ligands are discussed. Possible routes leading to 6α-[18F]fluoroprogestins are presented in chapter four. The radiochemical approaches towards the synthesis of these ligands are discussed. In chapter five the proposed routes to the fluorine-18 labelled β1-adrenergic ligands are described and evaluated in the synthesis of two model compounds. 1-[18F]fluorometoprolol, the [18F]fluorinated analogue of a potent beta-blocker, is prepared using one of the investigated methods. The biological effect of fluorine substitution of a β1-adrenergic ligand is discussed on the basis of an in vitro and in vivo evaluation. 21 figs., 28 schemes, 19 tabs., 182 refs