SeriesNuclear medicine in neurology and psychiatry
Section snippets
Clinical developments
Panel 1 summarises the main areas of clinical interest and panel 2 shows a selected list of ligands.
Drug discovery and evaluation
The cost of developing a new drug has been estimated at $300 million over 10 years. Combinatorial chemistry and rapid screening methods may identify promising candidates, but they cannot provide details of bioavailability, pharmacokinetics, toxicity, or specificity. Early identification of promising drugs would facilitate ethical animal and clinical research and reduce development costs. Until recently drug action at neuroreceptor targets had to be deduced from in-vitro studies on animal or
Schizophrenia
The D2 receptor blockade hypothesis of antipsychotic drug action suggested a highly specific, linear relation between antipsychotic efficacy, and blockade of striatal D2 receptors.31, 32 Until recently, drug development strategies followed the rule that potent D2 receptor antagonism was an absolute requirement. Initial studies with PET supported this view.33 However, a series of “hypothesis busting” studies has challenged this simple relationship.33, 34 High stratial D2 receptor occupancy
Parkinson's disease
Presynaptic dopamine markers such as 18F-levodopa (PET) and 123I-labelled CIT or FP-CIT (SPET) provide reliable estimates of nigrostriatal degeneration.39 The impact of experimental treatments for Parkinson's disease (including fetal cell transplantation or antioxidative neuroprotective strategies) has been monitored with these tools. Peripheral decarboxylation is a problem with levodopa. Peripheral carboxymethyltransferase inhibition by drugs such as entacapone increases the bioavailability of
Cocaine addiction
The magnitude of the “high” after cocaine ingestion closely correlates with the degree of blockade of the dopamine transporter in man,42 and this blockade effect seems to be a necessary, but not sufficient, explanation for the cocaine “high”.43 Treatment strategies could focus on preventing cocaine's rapid blockade of the dopamine transporter or on inhibiting its central effects through other pathways. Dewey and colleagues44 have used PET in non-human primates to show that
References (43)
- et al.
PET imaging of cerebral perfusion and oxygen consumption in acute ischaemic stroke: relation to outcome
Lancet
(1993) - et al.
Brain SPECT findings in late whiplash syndrome
Lancet
(1995) - et al.
Clozapine, single photon emission tomography and the D2 dopamine receptor blockade hypothesis of schizophrenia
Lancet
(1992) - et al.
Central D2 dopamine receptor occupancy in relation to antipsychotic drug effects: a double blind PET study of schizophrenic patients
Biol Psychiatry
(1993) - et al.
Limbic selectivity of clozapine
Lancet
(1997) - et al.
Brain single-photon emission computed tomography
Neurology
(1994) Imaging the mind
Sem Nucl Med
(1998)- et al.
Prognostication of recovery following stroke using the comparison of CT and Technetium-99m HM-PAO SPECT
J Nucl Med
(1990) - et al.
Spontaneous reperfusion after ischemic stroke is associated with improved outcome
Stroke
(1998) - et al.
Predictive value of brain perfusion single-photon emission computed tomography in acute ischemic stroke
Stroke
(1990)