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Brain, Vol. 116, No. 3, 497-510, 1993
© 1993 Guarantors of Brain

research-article

Loss of brain 5-HT2receptors in Alzheimer's disease

In vivo assessment with positron emission tomography and (18)setoperone

Jérôme Blin1,2, Jean Claude Baron3, Bruno Dubois2, Christian Crouzel1, Marco Fiorelli1, Dominique Attar-Lévy1, Bernard Pillon2, Denis Fournier1, Marie Vidailhet2 and Yves Agid2

1Service Hospitalier Frédéric Joliot Orsay 2INSERM U289 et Service de Neurologie et de Neuropsychologie. Hôpital de la Salpêtrière Paris 3INSERM U320, Caen France

Using 18[18F]setoperone and positron emission tomography (PET), alterations in serotonergic 5-HT2 receptor binding were studied in cerebral cortex of nine unmedicated patients with probable Alzheimer's disease and 37 healthy controls. The kinetics of unchanged radioligand in plasma and 18F-radioactivity in blood and brain were obtained for 90 min following tracer injection. The specific binding of [18F]setoperone to 5-HT2 receptors in the cerebral cortex was quantitated by subtraction using cerebellum as reference. In controls, a significant reduction in specific binding was associated with age and similar linear regression slopes were obtained in all the cortical regions studied. No significant difference was observed between patients with Alzheimer's disease and age-matched controls in the injected mass of setoperone, percentage of unmetabolized18setoperone in plasma, 1818F-radioactivity in blood fractions and cerebellar 18F-radioactivity concentration, indicating similar non-specific brain kinetics and metabolism of the radioligand. In contrast, there was a significant reduction in specific [18setoperone binding in the cerebral cortex in patients with Alzheimer's disease relative to control values (temporal, 69% frontal, 69% parietal, 55% temporo-parietal, 54% occipital cortex, 35%). The results demonstrate that the loss in 5-HT2 receptor binding in the cerebral cortex of patients with Alzheimer's disease, long documented by post-mortem studies, can now be assessed in vivo using PET.

Correspondence to: Jé rð me Blin, Nouvelle Pharmacie U289, Hðipital de la Salpêtrière, 75651 Paris Cedex 13, France.

Received August 19, 1992. Revised November 2, 1992. Accepted November 25, 1992.


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