FluoroDOPA

The dopaminergic system plays a role in the brain on motor and cognitive functions (Parkinson’s disease) and psychiatric disorders (schizophrenia, depression, addiction).

The action of the endogenous neurotransmitter dopamine takes place within the dopaminergic neurons, which innervate the forebrain. The neurons are located in two nuclei in the brainstem, substantia nigra and ventral tegmental area.

From these areas the neurons project to several other brain regions. Dopamine is formed by hydroxylation and decarboxylation of L-tyrosine. After its synthesis in the cytoplasm, dopamine can be released in the synapse through vesicles. The action of dopamine takes place by binding to postsynaptic dopamine receptors, resulting in formation of second messengers. The action of the neurotransmiter is terminated by reuptake in the presynaptic nerve terminals through the dopamine reuptake site (dopamine transporter, DAT). Otherwise, dopamine may be partly metabolized in the synaptic cleft.

Since the first PET-study of dopamine metabolism in the human brain with 6-[18F]fluoro-L-3,4- dihydroxyphenylalanine (6-[18F]FDOPA) [11], this PET tracer has been extensively used for investigating presynaptic function in brain disorders. From three different ring fluorinated analogues of L-3,4-dihydroxyphenylalanine (LDOPA), 6-[18F]FDOPA was selected as the most potent tracer for PET because of a relatively low affinity for catechol-O-methyltransferase and a relatively high affinity for aromatic amino acid decarboxylase.

6-[18F]FDOPA is furnished by a direct electrophilic radiofluorination followed by HCl-hydrolysis for deprotection and HPLC separation using a  physiological phosphate buffer.