Positron emission tomography (PET) can be used to monitor in vivo translocator protein (TSPO) expression by using specific radioligands. Recently, several [11C]PK11195 analogues have been synthesized to improve binding stability and brain availability. [18F]VC701 was synthesized and validated in CD healthy rats by biodistribution and inhibition analysis. Imaging studies were also conducted on animals injected unilaterally in the striatum with quinolinic acid (QA) to evaluate the TSPO ligand uptake in a neuroinflammation/neurodegenerative model. [18F]VC701 was synthesized with a good chemical and radiochemical purity and specific activity higher than 37 GBq/μmol. Kinetic studies performed on healthy animals showed the highest tracer biodistribution in TSPO-rich organs, and preadministration of cold PK11195 caused an overall radioactivity reduction. Metabolism studies showed the absence of radiometabolites in the rat brain of QA lesioned rats, and biodistribution analysis revealed a progressive increase in radioactivity ratios (lesioned to nonlesioned striatum) during time, reaching an approximate value of 5 4 hours after tracer injection. These results encourage further evaluation of this TSPO radioligand in other models of central and peripheral diseases.
Emission tomography techniques and, in particular, positron emission tomography (PET) enable the in vivo study of several physiological and neurochemical variables in human subjects using methods originally developed for quantitative autoradiography. In particular, PET allows one to evaluate in human subjects: (a) the effect of specific neurochemical challenges on regional brain function at rest or under activation; (b) the activity of neurotransmitters and the regional expression of specific molecular targets during pathology including their modulation by drug treatment; (c) the kinetics of drug disposition and activity directly in the target organ. This is of primary interest in the field of biological psychiatry and in psychoactive drugs development, where it is particularly difficult to reproduce human diseases using animal models in view of the peculiarity of this field and the large heterogeneity of each psychiatric illness also inside the same clinical definition. The aim of this paper is to review the principal strategies and the main results of the use of PET or single photon emission tomography (SPET) molecular imaging for the in vivo study of serotonin receptors and the main results obtained from their application in the study of major depression. Keywords: SEROTONIN RADIOLIGAND, psychiatric disorders, SERT binding sites, Fluvoxamine, paroxetine, depression
The authors have evaluated the efficacy and tolerability of ciprofloxacin, a new broad-spectrum fluor-quinolone, in the therapy of gastrointestinal infections. The authors have studied 24 patients suffering from above-mentioned infections clinically diagnosed (11 microbiologically diagnosed too). All the patients took ciprofloxacin tablets 500 mg b.i.d. for 10 days (average). All the patients were restored to health and the tolerability was excellent.
3-Quinolinecarboxamides have been synthesized and evaluated for their binding to the human NK(1) receptor. Several secondary amide derivatives show NK(1) receptor affinity in the picomolar range. The most active compound, hydroxymethylcarboxamide 3h showing an IC(50) value in the subpicomolar range, behaved as an agonist of NK(1) receptor in endothelial cell proliferation, inositol phosphate turnover, and NO-mediated cyclic GMP accumulation, thus proving it to be the first non-peptide NK(1) receptor agonist showing very high potency.
