p-[18F]MPPF, 5-HT1A antagonist: comparison to [3H]8-OH-DPAT with autoradiography

in Society for Neuroscience / Abstracts (1999)

p-MPPF 4-(2’-methoxyphenyl)-1-[2’-[N-(2’’-pyridinyl)-p-fluorobenzamido] ethyl]piperazine is the para-fluorobenzoyl analog of the highly selective 5-HT1A antagonist WAY-100635. The one step procedure used ... [more ▼]

p-MPPF 4-(2’-methoxyphenyl)-1-[2’-[N-(2’’-pyridinyl)-p-fluorobenzamido] ethyl]piperazine is the para-fluorobenzoyl analog of the highly selective 5-HT1A antagonist WAY-100635. The one step procedure used to label p-MPPF with fluorine-18 (cyclotron produced positron emitter of 110 min half-life) leads to a radiopharmaceutical compound easily prepared on a large scale. The preliminary evaluations conducted in rats and cats are good reason to consider p-[18F]MPPF as an interesting reversible radioligand to study the 5-HT1A receptor family in humans with positron emission tomography (PET). In this paper we report a careful comparison between p-[18F]MPPF and [3H]8-OH-DPAT with autoradiography and quantitative densitometry in the same animal. All experiments were conducted in Sprague Dawley male rats. For p-[18F]MMPF, the results were obtained ex-vivo after an intravenous injection of high specific activity radioligand (0.8-1.5 Ci/µmol) in vigil (no anesthesia), free moving and unstressed animals. For the purpose, permanent cannulation of the posterior vena cava were realized at least four days in advance. The [3H]8-OH-DPAT results were obtained in vitro on adjacent coronal sections to the one used for the p-[18F]MPPF autoradiography. Quantitative densitometry was employed to compare the values obtained in relevant brain structures (frontal cortex, lateral septum, hippocampus, dorsal raphe, entorhinal cortex and cerebellum). The plot of the p-[18F]MPPF values obtained for each structure against the [3H]8-OH-DPAT results displayed a significant linear correlation. These results demonstrate that from a qualitative as well as quantitative point of view, the binding of p-[18F]MPPF is totally comparable to the one of [3H]8-OH-DPAT. Supported by grants from INSERM/CGRI and FNRS Belgium. [less ▲]

Le p-[18F]MPPF: un nouveau ligand pour l'étude par TEP des récepteurs 5-HT1A

Poster (1997, May 25)

Tissue distribution, autoradiography and metabolism in rats of p-[18F]MPPF: 5-HT1A antagonist.

in Journal of Labelled Compounds & Radiopharmaceuticals (1997), 40

Evaluation of p-[18F]MPPF, 5-HT1A antagonist, a potential radiopharmaceutical for PET: tissue distribution, autoradiography and metabolism in rats.

in Society for Neuroscience / Abstracts (1997), 23

Combined study of cerebral glucose metabolism and [11C] methionine accumulation in probable Alzheimer's disease using positron emission tomography

in Journal of Cerebral Blood Flow & Metabolism (1996), 16(3), 399-408

There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result ... [more ▼]

There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result from local neuronal loss or from a decrease of synaptic activity. We measured in vivo [11C]methionine accumulation into proteins with positron emission tomography (PET) to assess cortical tissue loss in AD. Both global regional activity and compartmental analysis were used to express [11C]methionine accumulation into brain tissue. Glucose metabolism was measures with [18F]fluorodeoxyglucose and autoradiographic method. Combined studies were performed in 10 patients with probable AD, compared to age-matched healthy volunteers. There was a significant 45% decrease of temporo-parietal glucose metabolism in patients with AD, and frontal metabolism was lowered in most patients. Temporo-parietal metabolism correlated to dementia severity. [11C]methionine incorporation into temporo-parietal and frontal cortices was not significantly decreased in AD. There was no correlation with clinical symptoms. Data suggest that regional tissue loss, assessed by the decrease of [11C]methionine accumulation, is not sufficient to explain cortical glucose hypometabolism, which reflects, rather, reduced synaptic connectivity. [less ▲]

Frontal activation observed with PET in visual discrimination involving duration or intensity parameters

in Proceedings of the sixth meeting of the European Neurological Society, Tutzing (Munich), RFA, June 17-21 (1995)

Glucose hypometabolism in Alzheimer's disease is not related to loss of cortical interneurons bearing 5HT2 receptors.

in Acta Neurologica Belgica (1995), 95

Differential diagnosis of Alzheimer's disease with PET.

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (1994), 35(3), 391-8

PET studies have demonstrated bilateral temporo-parietal hypoperfusion and hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other dementias ... [more ▼]

PET studies have demonstrated bilateral temporo-parietal hypoperfusion and hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other dementias. METHODS: To evaluate the diagnostic power of cerebral metabolic distribution patterns for "cortical" degenerative dementias, PET scans obtained from 129 patients referred for differential diagnosis of dementia were analyzed visually. RESULTS: Sixty-five patients had a final clinical diagnosis of probable AD. Ninety-seven percent (97%) of those had abnormal metabolic scans and 94% showed a suggestive pattern of bilateral or unilateral temporo-parietal hypometabolism (with or without frontal involvement). Hypometabolism was unilateral in 23% of patients. Five subjects with a neuropathologically proven diagnosis of Alzheimer's disease had a suggestive metabolic pattern. One of those was an early case with frontal hypometabolism exceeding temporo-parietal involvement. Two patients with Alzheimer's-type dementia had isolated bilateral frontal hypometabolism. CONCLUSIONS: This alternative metabolic pattern may correspond to a non-Alzheimer pathology occurring in 10%-20% of patients suffering from clinically probable Alzheimer's disease. Most of the patients with possible but atypical Alzheimer's-type dementia showed isolated bilateral frontal involvement. This metabolic pattern probably corresponds to different diseases, such as Pick's disease, frontal lobe dementia or progressive subcortical gliosis. [less ▲]

N.C.A. asymmetric syntheses of a-methyl and b-hydroxy a-amino acid labelled with fluorine-18 for probing enzymatic function.

in Journal of Labelled Compounds & Radiopharmaceuticals (1994), 35

Robot-assisted synthesis of [18F]altanserin, 4-[18F]fluorotropapride, 6-[18F]fluoro-L-dopa and 2-[18F]fluoro-L-tyrosine.

in Journal of Labelled Compounds & Radiopharmaceuticals (1994), 35