Serotonin-1A (5-HT(1A)) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[ N-(2"-pyridinyl)- p-[(18)F]fluorobenzamido] ethyl] piperazine ( p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT(1A) receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT(1A) receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT(1A) receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT(1A) receptor human studies.
In order to launch a new transplantation program for Parkinson''s disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD. Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Creteil (France). The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen. Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 µl of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the ‘on’ periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson''s Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of 18F-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.
Brain glucose metabolism was investigated with PET and ['8F]fluorodeoxyglucose, before and after a bifrontal stereotactic leukotomy in a 37 year old woman with refractory obsessive-compulsive disorder. A bilateral decrease in glucose metabolism was found in the orbital frontal cortex after psychosurgery. Glucose metabolism was decreased to a lesser degree in Brodmann's area 25, in the thalamus, and in the caudate nucleus. Clinical improvement in obsessive-compulsive disorder after stereotactic tractotomy seems to be associated with metabolic changes in the brain, in particular, in the orbital part of the frontal lobe.
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