[(18)F]P-Mppf: Aa Radiolabeled Antagonist for the Study of 5-Ht(1a) Receptors with Pet

in Nuclear Medicine & Biology (2000), 27(5), 467-71

This paper summarizes the present status of the researches conducted with [(18)F]4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido ]ethyl]-piperazine known as [(18)F]p-MPPF, a new 5-HT(1A ... [more ▼]

This paper summarizes the present status of the researches conducted with [(18)F]4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido ]ethyl]-piperazine known as [(18)F]p-MPPF, a new 5-HT(1A) antagonist for the study of the serotonergic neurotransmission with positron emission tomography (PET). This includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with autoradiography and PET, human data with PET, toxicity, and metabolism. [less ▲]

Tissue distribution, autoradiography, and metabolism of 4-(2'-methoxyphenyl)-1-[2' -[N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist for positron emission tomography: An In vivo study in rats.

in Journal of Neurochemistry (2000), 75(2), 803-11

The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving ... [more ▼]

The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving rats. Biodistribution studies showed that the carbon-fluorine bond was stable in vivo, that this compound was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great quantity of highly polar metabolites found in plasma did not contribute to the small amounts of metabolites found in hippocampus, frontal cortex, and cerebellum. Exvivo p-[(18)F]MPPF and in vitro 8-hydroxy-2-(di-n-[(3)H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p-[(18)F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT(1A) receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p-[(18)F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT(1A) specificity of p-[(18)F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT(1A) binding sites in the brain. [less ▲]

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

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (1997), 38