FluoroDOPA

Guttman M, Leger G, Reches A, et al (1993) Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa. Movement Disord 8 298-304... 

Localisation of specific NT terminals. After its injection a labelled precursor should be taken up and detected in appropriate nerve terminals (and possibly cell bodies) so that the intensity of emission reflects the density of nerve terminals and the innervation. Using this procedure it has been possible to show that very little [ F] fluorodopa is concentrated in the striatum of Parkinsonian patients, compared with normals (Fig. 14.1). Whether the label remains on dopa or is transferred to dopamine will not greatly affect the result since both will label DA neurons although some will occur in noradrenergic nerve terminals. 

Recently PET studies with 6-fluorodopa, which is taken up by DA nerve terminals in the striatum and is therefore presumably a measure of both the number of functional DA neurons in the nigrostriatal tract to it as well as its DA content, show that this is more like 50% of normal at the start of symptoms, not the 80% observed at PM (see... 

A PET scan with [ F] fluorodopa in a control subject shows that the striatum is heavily labelled whilst in a Parkinson patient with established symptoms there is little labelling. This patient s twin, whilst free of symptoms, also showed some loss of labelling and subsequently developed the disorder. Reproduced by kind permission of D Brooks, MRC Cyclotron Unit, Hammersmith Hospital, UK. 

Sawle, G. V., Playford, E. D., Burn, D. J. et al. Separating Parkinson s disease from normality. Discriminant function analysis of fluorodopa F-18 positron emission tomography data. Arch. Neurol. 51 237-243,1994. 

Rosenberg NL, Myers JA, Martin WRW. 1989. Cyanide-induced parkinsonism clinical MRI and 6 fluorodopa Fd positron emission tomography pet studies. Neurology 39 142-144. 

In human subjects, Laakso et al. (2002) reported higher DA synthesis capacity in women than men on the basis of higher [ F] fluorodopa uptake in the sttiatum. Staley et al. (2001), using positron emission tomography (PET) imaging, found... 

C. Lemaire, M. Guillaume, R. Cantineau, A. Plevenaux, L. Christiaans, An approach to the asymmetric synthesis of L-6-[ F]fluorodopa via NCA nucleophilic fluorination, Appl. Radiat. Isot. 42 (1991) 629-635. 

F]-Fluoride-PET Imaging of bone metastases [ F]FET-PET Imaging with amino acids [ F]Fluorodopa-PET Imaging with amino precursors Acknowledgments References Note from the Editors... 

Ernst, M., Zametkin, A.J., Matochik, J.A., Jons, P.H., and Cohen, R.M. (1998) DOPA decarboxylase activity in attention deficit disorder adults. A [fluorine-18]fluorodopa positron emission tomographic study. / Neurosci 18 5901-5907. 

Propanoic Acid (5-Fluorodopa) 2-Amino-3-(4,5-dlmetlioxy-3-fluoro-phenyl)- ElOb,. 248 (N-Ac - NH)... 

Solid-phase electrophilic fluorination was previously used by Luthra [1] to prepare an F-L-dopa analogue, (1), for the in sim release of F-L-fluorodopa. 

Figure 14.6 Nucleophilic approach to synthesis of 6-[18F]fluoroDOPA. The multistep synthesis introduces fluorine-18 in an initial nucleophilic aromatic substitution reaction.

Remy, P, Samson, Y., Hantraye, P., et al. (1995) Clinical correlates of F-18 fluorodopa uptake in 5 grafted Parkinsonian-patients. Annals of Neurology, 38(4), 580-588. 

Scheme 4.41 Synthesis of different [ F]fluorodopa isomers [90] used for diagnosis of brain disorders, for example Parkinson s disease.

Figure 8.2. Molecular structures of (a) 6-18F-L-fluorodopa, (b) nC-flumazenil, (c) uC-methylspiperone, (d) uC-L-methionine, (e) nC-raclopride, (f) 18F-fluoromiso-nidazole (Reprinted with the permission of The Cleveland Clinic Center for Medical Art Photography 2009. All Rights Reserved)...

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