Ligands and tracers for PET studies of the 5-HT system--current status.

The status of the radiochemical development and biological evaluation of radioligands and tracers for PET studies of the serotonergic system is reviewed, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies of central 5-HT2 receptors, namely [18F]setoperone and [18F]altanserin. Though, it has not proved possible to recommend tracers or radioligands for the study of other aspects of serotonergic system, prospects for future radiochemical development are indicated, especially for developing radioligands for the 5-HT re-uptake site, and for the 5-HT1 and 5-HT3 receptors

Figures du démoniaque, hier et aujourd’hui

Le « retour de Satan », observable aujourd'hui en des manifestations fort diverses, pourrait bien renvoyer à la redécouverte, bruyante ou quotidienne, à la suite d'évènements terrifiants ou d'une déréliction sans remède au plan de l'histoire d'un « abîme noir » en l'humain. Redécouverte qui se laisse appréhender comme un double brouillage d'identité : l'image de Dieu oscille entre un versant positif et un versant négatif et l'humain s'en trouve comme traversé d'une fêlure, voire dédoublé. Si la foi toute chrétienne tient, tout entière, à la reconnaissance d'un salut gratuitement donné dans l'Événement christique insondable comme tel, comment fait-elle droit à la dimension d'épreuve, de combat, mais aussi à l'impératif de solidarité sans lesquelles la réalité et l'annonce du salut seraient privées de signification et de résonance ? Tels sont la question et l'enjeu de la session théologique, tenue aux F.U.SL. en 1991. Le parcours proposé comporte deux étapes : des mises en situation historiques - restitution de synthèses doctrinales et de glissements historiographiques - et anthropologiques font écho et interrogent des apports exégétiques, éthiques et théologiques visant à préciser ce qui nous est suggéré, à travers les figures du démoniaque, de ce qu'il peut advenir de la liberté humaine lorsqu'elle se retourne vers « Celui qui a, par la Croix, vaincu le Prince de Monde »

Amino acids for the measurement of protein synthesis in vivo by PET.

In principle, PET in combination with amino acids labelled with positron-emitting radionuclides and kinetic metabolic models, can quantify local protein synthesis rates in tissue in vivo. These PET measurements have clinical potential in, for example, oncology, neurology and psychiatry. An optimal positron-emitting amino acid for the measurement of PSR has a high protein incorporation, can easily be prepared by automated equipment and has minimal non-protein radioactive metabolites. Presently L-[methyl-11C]methionine, L-[1-11C]leucine, L-[1-11C]tyrosine, L-[1-11C]phenylalanine, L-[1-11C]methionine and L-[2-18F]fluorotyrosine are under evaluation in normal volunteers and/or in patients. Several other amino acids are suggested. No comparison of the clinical usefulness of the different amino acids in man is yet available. Because of the longer half life of 18F compared to 11C, [18F]fluoro amino acids may have advantages over [11C]amino acids for the investigation of tissue with relative slow protein synthesis, such as brain, and for application in institutions with an off site, but nearby cyclotron. The half life of [13N]amino acids is considered to be too short for flexible clinical application. As yet no metabolic compartmental model has been investigated for [13N]amino acids. For routine application reliable preparation of the radiopharmaceutical is essential. Of all the amino acids under evaluation, a reliable, high yield, easy to automate production procedure is available for L-[methyl-11C]methionine only. It is however unlikely that this tracer can accurately measure PSR because of its non-protein metabolism. For the other amino acids the main problems in production are associated with complex multistep syntheses and/or low radiochemical yields, complex purification methods and the need to isolate the L-enantiomer. The kinetic metabolic models under investigation, consist of 4 or 5 compartments depending on the necessity to compensate for labelled metabolites. The metabolic profile of the amino acids is mainly extracted from animal experiments. Because of the number and amount of labelled metabolites in plasma, [11C]carboxylic labelled amino acids are preferred to amino acids with carbon-11 in another position. As yet no recommendation can be given on the optimal labelled amino acid(s) for PSR measurement in vivo nor on the methods to prepare the amino acids reported for this purpose

Preliminary evaluation of 2-[4-[3-(tert-Butylamino)-2-hydroxypropoxy]phenyl]-3-methyl-6-methoxy-4(3H)-quinazolinone ([±]HX-CH 44) as a Selective β1-Adrenoceptor Ligand for PET

International audience(+/-)-3-[11C]Methyl-2-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-6 -methoxy-4(3H) quinazolinone ([+/-]-[11C]HX-CH 44) was labeled with carbon-11 using [11C]iodomethane with the corresponding N-demethylated precursor. Then, 30-90 mCi (1.10-3.33 GBq) of pure [11C]HX-CH 44 were obtained 30 min after end of bombardment with specific radioactivities of 500-1,400 mCi/micromol (18.5-51.8 GBq/micromol). Myocardial uptake in dogs was 0.340+/-0.043 pmol/mL tissue per nanomole injected, 10-15 min postinjection. Heart-to-lung ratio was 3 from the 5th to the 30th minute. Only 35% of the myocardial radioactivity could be displaced. Tissue uptake could not be blocked with appropriate compounds. Therefore, (+/-)-[11C]HX-CH 44 does not appear to be a suitable ligand for the study of myocardial beta1-adrenoceptors in positron emission tomography