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

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.