Transition from Saltation to Collisional Regime in Windblown Sand.

We report experiments on windblown sand that highlight a transition from saltation to collisional regime above a critical dimensionless mass flux or Shields number. The transition is first seen through the mass flow rate Q, which deviates from a linear trend with the Shields number and seems to follow a quadratic law. Other physical evidences confirm the change of the transport properties. In particular, the particle velocity and the height of the transport layer increases with increasing Shields number in the collisional regime while the latter are invariant with the wind strength in the saltation regime. Discrete numerical simulations support the experimental findings and ascertain that mid-air collisions are responsible for the change of transport regime.

Theory of mind, empathy and emotion perception in cortical and subcortical neurodegenerative diseases.

Although the impact of neurodegenerative diseases on everyday interactions is well known in the literature, their impact on social cognitive processes remains unclear. The concept of social cognition refers to a set of skills, all of which are essential for living in a community. It involves social knowledge, perception and processing of social cues, and representation of mental states. This report is a review of recent findings on the impact of cortical and subcortical neurodegenerative diseases on three social cognitive processes, namely, the theory of mind, empathy and processing emotions. The focus here is on a conceptual approach to each of these skills and their cerebral underpinnings.

Discrepancy between social and nonsocial decision-making under uncertainty following prefrontal lobe damage: the impact of an interactionist approach.

Deficits in decision-making are thought to contribute significantly to socio-behavioral impairments of patients with frontal lobe damage. The purpose of this study was to test the hypothesis of whether the inappropriate social behavior of patients with frontal lesions can be viewed as the product of a general failure of decision-making ability or as the result of socio-cognitive impairment. We studied a group of patients with prefrontal lesions (FL patients, n = 15) and a group of matched healthy controls (n = 30) on the Iowa Gambling task (IGT) of nonsocial decision-making, environmental dependency phenomena (EDP) during social interaction, and the "reading the mind in the eyes" and "character intention task" of theory of mind (TOM) tasks. The FL patients were impaired in both TOM and EDP protocols but, surprisingly, they behaved appropriately in the IGT. In addition, FL patients with EDP did not differ in executive functioning, IGT and TOM measures from those who did not demonstrate these behavioral disorders. The right orbitofrontal cortex was associated with social decision-making deficits. By adopting an interactionist approach, this study raises the possibility of identifying components of social and nonsocial decision-making, which could be helpful in understanding the behavioral disorders of FL patients.

A contribution to the study of environmental dependency phenomena: the social hypothesis.

Environmental dependency phenomena refer to the symptoms initially described by Lhermitte (1983, 1984) under the terms of "utilization behavior" and "imitation behavior". These clinical signs are linked to essential notions such as free-will and human autonomy, and seem to be specific of the frontal pathology. Surprisingly, few studies have addressed these symptoms and inconsistent definitions are available. To investigate the theoretical and clinical definitions of environmental dependency phenomena, three groups of neurological patients (n=60) with frontal, subcortical, and posterior brain lesions were compared. Clinically, our findings help to rehabilitate the definitions of Lhermitte (1983, 1984) and challenge the classical interpretation in terms of an executive control deficit. The frontal specificity of the disorders and the lack of relation between executive/behavioral deficits were supported. The right orbitofrontal cortex seems particularly involved in environmental dependency. These results offer some evidences for differentiate two historical concepts of neuropsychology, namely the "frontal" and "dysexecutive" syndromes. A new interpretation of environmental dependency phenomena is provided which could be helpful to orient the neuropsychology of frontal syndrome.

Utilization behavior: clinical and theoretical approaches.

Lhermitte (1983) coined the term "utilization behavior" (UB) to define a neurobehavioral syndrome in which the visuo-tactile presentation of objects compels patients to grasp and use them, despite the fact that they have not been instructed to do so. The author suggested that UB was the consequence of frontal lobe damage. Thereafter, Shallice, Burgess, Schon, and Baxter (1989) questioned Lhermitte's (1983) procedure for eliciting UB, putting forward an alternative research methodology that led to differentiate two forms of UB: "induced" and "incidental." To date, there has been no direct comparison between these two procedures, nor have any other methodologies been used to explore this clinical sign, which is related to fundamental concepts such as free will and human autonomy. We investigated UB in 70 subjects (25 patients with frontal lobe lesions, 10 patients with posterior brain damage and 35 control subjects) using the methodologies of Lhermitte (1983) and Shallice et al. (1989), as well as an original "verbal generation" procedure. Our results show that the verbal generation procedure reveals UB efficiently and that elicitation of this sign appears to be directly linked to the content of the task. We discuss the interpretation of UB in terms of an executive control deficit.

Does the chicken genotype 'Géline de Touraine' have specific carcass and meat characteristics?

The aim of this study was to determine the specific characteristics of carcass and meat from an old French chicken breed, the 'Géline de Touraine' (GT), characterised by a very slow-growing rate and usually slaughtered at 120 days of age. For this purpose, we compared the GT with an experimental crossbreed (EC) exhibiting the same growth rate, and with a 'Label rouge' (LR) genotype usually slaughtered at 84 days of age. A total of 250 males and 250 females per genotype were reared by separating sexes and genotypes. The growth performances were recorded. At 84 days of age, 80 birds per sex and per genotype were slaughtered. The frequency of clawing and pecking injuries on the carcass was noted. We also measured the skin colour and the thickness of wing membrane. The relative percentages of carcass, breast, thigh + drumstick, abdominal fat, testis or ovary to body weight were determined. On breast and thigh muscles the ultimate pH (pHu) and colour were measured. The juice loss after 3 days' storage at +4°C and after cooking at 85°C, and the shear force value of Warner-Bratzler were only measured on breast muscles. At 120 days of age, we repeated the same measurements but only on EC and GT genotypes in order to compare birds at the same age or at the respective slaughter age for each production. Whatever the slaughter age, the body weight of males was always higher than that of the females but the carcass yield was similar for both sexes. The females had higher breast yield and carcass fatness but lower thigh + drumstick yield than the males. The yellowness of skin and meat was higher for the females than for the males while the contrary was observed for the redness of the meat. The breast meat of the females also had higher cooking loss than that of the males. GT and EC birds exhibited a higher occurrence of carcass defects and a higher pHu in meat than LR birds. The GT chickens were characterised by a lower breast yield, a higher fattiness and an earlier sexual maturity than the other genotypes, which could confer typical sensorial attributes to their meat. Finally, the EC chickens exhibited a skin and a meat more coloured than the other genotypes, particularly for yellowness, a character which could be under genetic control.

Increasing dietary lysine increases final pH and decreases drip loss of broiler breast meat.

Responses to increased dietary Lys concentrations were evaluated on 1,584 Ross 308 male broilers between 21 and 42 d of age housed according to 2 bird densities. The experimental design was composed of 8 factorial treatments: 2 bird densities (22 or 44 broilers/ 1.7 m(2) pen) x 4 true digestible (TD) Lys levels (0.83, 0.93, 1.03, and 1.13%). There were 6 repetitions per treatment. Birds were weighed individually at d 21 and 42. Feed consumption was recorded per pen. Body weight gain and feed conversion were calculated over the experimental period. Forty-eight broilers per treatment were dissected at 42 d of age. Final pH and drip loss during storage were measured on the pectoralis major. Density adversely affected feed intake (169 +/- 1 and 160 +/- 1 g/d with 22 and 44 birds per pen, respectively, P < 0.05), growth rate (97.4 +/- 0.5 and 91.0 +/- 0.7 g/d, P < 0.05), and feed conversion (1.730 +/- 0.008 and 1.760 +/- 0.006, P < 0.05). Except for feed intake, there was no interaction between the effects of bird density and dietary Lys. An increase in dietary TD Lys from 0.83 to 0.93% resulted in an increased growth rate (from 91.8 +/- 1.6 to 95.5 +/- 0.8 g/d, P < 0.05), improved feed conversion (from 1.783 +/- 0.008 to 1.742 +/- 0.009, P < 0.05), and increased breast meat yield (22.0 +/- 0.1% to 22.7 +/- 0.2%, P < 0.01). Performance and body composition traits were not significantly improved for concentrations of TD Lys higher than 0.93%. However, final breast pH increased from 0.83 up to 1.03% TD Lys in the diet (6.02 +/- 0.01 vs. 5.91 +/- 0.01, P < 0.05), and drip loss correlatively decreased (0.85 +/- 0.03% vs. 1.10 +/- 0.06, P < 0.05). This result opens new way of research for the definition of an amino acid requirement and on metabolic pathways involved in variations of breast muscle pH.

Semen cryopreservation for ex situ management of genetic diversity in chicken: creation of the French avian cryobank.

The need for semen preservation in domestic birds is a result of the reduction in genetic variability of domestic bird livestock and of the increasing risk of line extinction for health and safety reasons. Cryopreservation of embryos and primordial germ cells (PGC) is not routinely feasible in birds. The project therefore involved semen frozen in optimal safety and traceable conditions. Whole blood samples were also frozen to provide samples of analyses of genomes and health status. The feasibility of using ex situ conservation, i.e., collecting biological material to be stored outside the usual production area of the species (ex situ genetic stock), to preserve and manage rare breeds was tested with 4 subfertile populations: 3 rare experimental lines used for research into energy metabolism (R+), growth (Y33), and immunity (B4/B4), reared under known health status and the oldest endangered patrimonial French breed, the Gauloise dorée with an unknown health status. A general infrastructure was set up for the health screening and remediation of diseases, collection and storage of frozen cells and 2 sites were created for the storage of frozen samples. The screening and remediation of diseases of the Gauloise dorée, which was contaminated with various Salmonella and Mycoplasma strains, was achieved by successive treatment of parents, incubated eggs and young chicks with Baytril followed by Tiamulin. For each line, 474 to 994 semen straws have been frozen, thawed, and the semen evaluated. Insemination of frozen-thawed semen into females of the same genetic origin or of an egg-type commercial breed produced chicks in every case. For the most subfertile lines, insemination with egg-type females significantly increased the reproductive success. In conclusion, we report on the benefits of a semen and blood cryobanking complex for the management of endangered lines and strains of domestic birds. Current stocks made possible the restoration of more than 96% of the initial genome. This project also provided technical solutions to resolve some of the health problems frequently encountered for gene preservation in poultry.

Effects of wheat quality on digestion differ between the D+ and D- chicken lines selected for divergent digestion capacity.

The aim of the experiment was to study the effects of 2 wheat cultivars (Baltimor and Scipion) with different hardness values (75 and 5, respectively) on 2 divergent lines (D+ and D-) of broiler chickens selected on the basis of their digestion ability assessed by AME(n). Wheat was incorporated at 54.6% in diets. The other main ingredients were soybean meal (35.3%) and rapeseed oil (5.5%). Diets were given as pellets from 7 to 26 d. The experimental design was a 2 x 2 factorial design testing 2 wheat cultivars (soft or hard) on 2 selected lines of broiler chickens (high AME(n) or low AME(n)). From 7 to 16 d, D+ line showed lower (P < 0.0001) feed intake and feed:gain ratio than the D- line. At 3 wk of age, the D+ chickens resulted in increased digestibility values (P < 0.01) and 9% increased AME(n) value (P < 0.0001) compared with D-. Wheat cultivar effects on feed efficiency and AME(n) differed between lines. In the D+ line, their values were about 6% higher (P < 0.05) with soft than with hard wheat, whereas they did not differ in the D- line. However, wheat cultivar effect on starch digestibility did not differ between lines; soft instead of hard wheat resulted in about 6% improvement (P < 0.0001) in both lines. In the D- line, soft instead of hard wheat tended to reduce lipid and protein digestibilities, which explained why the starch digestibility improvement due to soft wheat was not converted into a significant AME(n) improvement in D birds. Study of digestive organ size revealed that increased proventriculus and gizzard weight (P < 0.05) could be one of the causes for the better digestion capacity of the D+ line. The pancreas was bigger (P < 0.01) in D- than in D+ birds, which probably came from an adaptation to a digestive disorder in D- birds.

Heritability of digestibilities and divergent selection for digestion ability in growing chicks fed a wheat diet.

The genetic parameters of digestibilities for a wheat-based diet were estimated on 864 broilers. Two divergent lines (D+ and D-) were developed based on AMEn. The Rialto wheat variety was used as it is known to result in low digestibility values. Digestibility of lipids (DL), starch (DS), and proteins (DP) were measured individually using Near Infrared (NIR) analysis of freeze-dried excreta. Body weight, feed consumption (FC), feed conversion ratio (FCR) and residual feed consumption (RES) were recorded to evaluate their correlation with AMEn. The mean AMEn value was 3,093 kcal/kg DM (CV = 9.0%), with a range of 1,001 to 4,022 kcal/kg DM, and was highly heritable (0.36 to 0.38) based on the Restricted Maximum Likelihood method. Genetic correlations with BW were low (-0.10 to -0.15). Selection for AMEn can thus be performed without modifying BW. In contrast, the estimated genetic correlations between AMEn and the other traits were highly negative (-0.53 to -0.60 for FC, -0.77 to -0.80 for RES, and -0.77 to -0.84 for FCR). Finally, digestibilities of feed components were moderately to highly heritable (0.33 to 0.47) and highly correlated with AMEn (0.91 for DL, 0.83 for DS, and 0.86 for DP). Selecting for improved AMEn should thus improve digestibility of proteins, starch, and lipids. The first generation of divergent selection on AMEn confirmed these results, D+ and D- lines showing a 13% difference in AMEn (P < 0.0001) and similar BW.

Quantitative analysis of striatal dopamine D2 receptors with 123 I-iodolisuride SPECT in degenerative extrapyramidal diseases.

123I-Iodolisuride has high specific affinity for binding on dopamine D2 receptors in the striatum and has been used in a few single photon emission computed tomography (SPECT) studies of extrapyramidal disorders. The diagnosis of Parkinson's disease (PD) is very difficult in the first 5 years of evolution, with 15-25% false positive diagnoses. The aim of this study was therefore to determine the value of iodolisuride SPECT in discriminating Parkinson's from the most frequent Parkinson-plus syndromes (PPS). Seventeen patients with an extrapyramidal syndrome had a SPECT examination 1 h after injection of 180-185 MBq of 123I-iodolisuride. They were followed under dopaminergic treatment for at least 2 years. After 2 years, they were separated in two groups according to specific clinical criteria and sensitivity to dopaminergic treatment: nine patients had PD (age = 59.8+/-8.8 years; Hoehn and Yahr = 1.8+/-0.7; evolution = 4.3+/-3 years) and eight had PPS (age = 71.6+/-7.3 years; Hoehn and Yahr = 2.9+/-2.0; evolution = 4.1+/-1.5 years). The binding potential of iodolisuride in the striatum was assessed by considering the striatum (S)/occipital lobe (O) ratio at the pseudo-equilibrium 1 h after injection. The S/O ratio was statistically different between PD and PPS (1.97+/-0.3 vs. 1.65+/-0.2 (P<0.02)). Iodolisuride SPECT could differentiate both groups with a sensitivity of 88.8% and a specificity of 75%. Iodolisuride is a good specific D2 receptor ligand for SPECT and complements specific clinical criteria for the diagnosis of Parkinson's disease and differentiation between different extrapyramidal disorders.

Synthesis of tropane and nortropane analogues with phenyl substitutions as serotonin transporter ligands.

The effects of structural modifications of 2 beta-carbomethoxy-3 beta-phenyl tropane analogues were evaluated on in vitro affinity to the dopamine (DAT) and serotonin (5-HTT) transporters in rat brain tissue. The introduction of a large alkyl group at the 4'-position of the phenyl ring, affording 2 beta-carbomethoxy-3 beta-(4'-alkylphenyl) tropane, diminished the affinity for the DAT whereas moderate 5-HTT affinity was obtained. The introduction of an iodine at the 3'-position of the 4'-alkylphenyl, affording 2 beta-carbomethoxy-3 beta-(3'-iodo-4'-alkylphenyl) tropane, and N-demethylation, affording 2 beta-carbomethoxy-3 beta-(3'-iodo-4'-alkylphenyl) nortropane, improved affinity and specificity for the 5-HTT. It could be assumed from these results that the combination of these three modifications of tropane structure yielded highly selective compounds for the 5-HTT. Of the new compounds synthesized, the most selective cocaine derivative, 2 beta-carbomethoxy-3 beta-(3'-iodo-4'-isopropylphenyl) nortropane (8d) labeled with iodine-123 or carbon-11, could be a potential ligand for exploration of the 5-HT transporter by SPET or PET.

Characterization of 99mTc-DTPA aerosols for lung permeability studies.

BACKGROUND: The interpretation of 99mTc diethylenetriamine pentaacetate (99mTc DTPA) aerosol clearance is based on the hypothesis that the 99mTc-DTPA complex is not altered by the nebulization process. OBJECTIVES: To characterize (1) the radiochemical purity (RCP) of 99mTc-DTPA and the stability of labeling after jet nebulization, and (2) the particle size distribution of the aerosol. METHODS: RCP and stability--the aerosol was driven by oxygen, captured on filters which were eluted and RCP was checked by thin layer chromatography. Particle size distribution--the aerosol was generated using dry air (50 psi) at three different flow rates, i.e. 3 (1 run), 6 (4 runs) and 9 l x min(-1) (4 runs). The mass median aerodynamic diameter (MMAD) and the geometric standard deviation (sigma(g)) were determined using a cascade impactor from the radioactivity counted on each stage. RESULTS: The RCP was more than 95% in all cases. Mean MMAD (+/-SD) was 0.70 microm (+/-0.07) at 9 l x min(-1), 0.93 microm (+/-0.05) at 6 l x min(-1) (p < 0.05) and 1.50 microm at 3 l x min(-1). Mean sigma(g) (+/-SD) was 2.02 (+/-0.08) at 9 l x min(-1), 2.00 (+/-0.16) at 6 l x min(-1) and 1.90 at 3 l x min(-1). CONCLUSION: This study demonstrates (1) that the high RCP of 99mTc-DTPA is not affected by jet nebulization, even when using oxygen at a high flow rate, and (2) that when using a flow rate between 6 and 9 l x min(-1), the MMAD remains optimal for peripheral lung deposition.

Microdialysis as a tool for in vivo study of dopamine transporter function in rat brains.

The role of dopamine as a major modulator of CNS function is well-known, and the homeostasis of dopamine is considered to be of major importance in the pathogenesis of several psychiatric and neurological diseases. Few methods are currently available for in vivo study of dopamine transporter function, which regulates extracellular levels of dopamine. Adapting the 'indicator diffusion' method applied to the microdialysis technique, we present here a suitable method for this functional investigation. We measured the cellular extraction of [3H]-MPP+, which is known to accumulate in the dopaminergic neurones through the DAT in the rat striatum, using [14C]-mannitol as reference substance characterized by absence of cellular accumulation. The cellular extraction was 0.41 and was almost abolished in the presence of the dopamine-uptake inhibitor cocaine, reaching 0.07. This suggested that extraction of [3H]-MPP+ was due to cellular uptake by dopamine transporters. Tissue analysis confirmed that [3H]-MPP+ was internalized in cells and that such transport was stopped by cocaine. Moreover, [3H]-MPP+ extraction was dramatically decreased after lesioning the nigro-striatal pathway with 6-hydroxydopamine, whereas [14C]-mannitol extraction was unchanged. It is concluded that the presented method can be used to study the functioning of the dopamine transporter in live animals.

Neuroprotection of nerve growth factor-loaded microspheres on the D2 dopaminergic receptor positive-striatal neurones in quinolinic acid-lesioned rats: a quantitative autoradiographic assessment with iodobenzamide.

Huntington's disease (HD) results from the degeneration of striatal neurones, mainly gamma-aminobutyric acid (GABA)ergic projection neurones and lately cholinergic interneurones. The use of trophic factors as agents able to prevent such neural degeneration is a promising strategy. The aim of this study was to validate nerve growth factor-loaded (NGF-loaded) poly-D,L-lactide-co-glycolide (PLGA) microspheres for treatment of HD in a rat model with quinolinic acid lesion using autoradiographic study of D2 dopaminergic receptors (D2R). This target is expressed by about half of striatal neurones and its scintigraphic exploration has already been performed for the follow-up of this degenerative process. Ex vivo autoradiography of D2R performed with iodobenzamide, the widely used ligand for single photo emission computerized tomography, revealed slight neuroprotection. Moreover, tolerance of microspheres was demonstrated by in vitro autoradiography with the marker of gliosis, [(3)H]-PK 11195.

Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids.

We studied the effects of a diet chronically deficient in alpha-linolenic acid, the precursor of long-chain n-3 polyunsaturated fatty acids, on dopaminergic neurotransmission in the shell region of the nucleus accumbens of rats. In vivo microdialysis experiments showed increased basal levels of dopamine and decreased basal levels of metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in awake rats from the deficient group compared to controls. The release of dopamine under KCl stimulation was similar in both dietary groups. By contrast, the release of dopamine from the vesicular storage pool under tyramine stimulation was 90% lower in the deficient than in the control rats. Autoradiographic studies in the same cerebral region revealed a 60% reduction in the vesicular monoamine transporter sites in the deficient group. Dopamine D(2) receptors were 35% increased in these rats compared to controls, whereas no change occurred for D(1) receptors and membrane dopamine transporters. These results demonstrated that chronic n-3 polyunsaturated fatty acid deficiency modifies several factors of dopaminergic neurotransmission in the nucleus accumbens. These findings are in agreement with the changes in dopaminergic neurotransmission already observed in the frontal cortex, and with the behavioral disturbances described in these deficient rats.

[131I]-TYR3-octreotide: clinical dosimetry and use for internal radiotherapy of metastatic paraganglioma and carcinoid tumors.

Dosimetry and therapeutic application of [(131)I]-Tyr3-octreotide were evaluated in three patients with metastatic paraganglioma and carcinoid tumor. The in vitro stability of [(131)I]-Tyr3-octreotide was verified. Tumor uptake and residence time were between 0.02 and 0.1% and 0.5 to 9.8 h, respectively. The calculated tumor radiation doses were between 0.105 and 0.696 mGy.MBq(-1). No intolerance or adverse effects were observed after the therapeutic doses (3.3-6.6 GBq). A partial tumor response was obtained in one patient and no response occurred in two patients.

Pharmacological characterization of (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)n ortropane as a selective and potent inhibitor of the neuronal dopamine transporter.

The pharmacological properties of the iodinated derivative of cocaine (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-me thylphenyl)nortropane (PE2I) were evaluated in vitro in the rat. Binding experiments on rat striatal membranes showed that PE2I selectively recognized the dopamine transporter (DAT) according to a single binding site model with high affinity (K(d) = 4 nM, B(max) = 12 pmol/mg protein). In the cortical membranes, the binding of PE2I was also selectively associated with the DAT (IC(50) for GBR 12909 = 6 nM versus more than 1000 nM for paroxetine), with similar affinity to that of the striatum. Autoradiographic experiments on rat brain sections with [(125)I]PE2I were in agreement with the localization of the DAT. In addition, PE2I was shown to be a potent inhibitor of dopamine uptake, with IC(50) values similar to those for GBR 12909 and 2beta-carbomethoxy-3beta-(4'-iodophenyl)-tropane (beta-CIT) (2-6 nM). All of these findings, combined with previously published data, support the use of PE2I as a selective and potent tool to study the DAT both in vivo and in vitro.

Luteinizing hormone measurement in polycystic ovary syndrome: a practical approach.

The biological diagnosis of polycystic ovary syndrome (PCO) remains questionable, and a single immunological hLH (ihLH) determination can be misleading. In order better to characterize these patients, we studied hLH pulsatility every 10 min for 4h using a radioimmunoassay and then compared the results with others we obtained with a biological method. Radioimmunological and biological profiles were similar in patients with PCO and in controls. We also studied pulsatility characteristics - frequency and amplitude - and calculated the area under the curve (AUC). There was no significant increase in frequency in our 10 patients with PCO but, as in other studies, increased amplitude of hLH pulses was observed. The most discriminating parameter was the AUC. For practical purposes, we propose that hLH in patients with PCO could be assessed efficiently by taking four samples every 10 min, with computerized calculation of the AUC.

PET examination of three potent cocaine derivatives as specific radioligands for the serotonin transporter.

Several positron emission tomography (PET) radioligands based on the aryl tropane structure have been used for studies on monoamine reuptake sites. RTI-364, RTI-330, and RTI-357 (3-beta-(4'-n-propyl-,4'-iso-propyl-, and 4'-iso-propenyl-phenyl)nortropane-2-beta-carboxylic acid methyl ester) are three recently synthesized cocaine analogues with higher affinity for the serotonin (5-HTT) than the dopamine transporter (DAT). Unlabelled RTI-364 and RTI-330 were prepared in a two-step synthesis. The key step was the addition of the appropriate propyl Grignard reagent to anhydroecgonine methyl ester. RTI-357 was prepared in a three-step synthesis with a palladium-catalyzed coupling reaction of beta-CIT and isopropenylzinc bromide as key step. Hydrolysis of the ester functions gave the carboxylic acid analogues of RTI-364, RTI-330, and RTI-357, which were labelled with 11C using [11C]methyl iodide in dimethyl formamide (DMF) and tetrabutylammonium hydroxide (TBAH) as base. All three compounds entered the monkey brain in a high degree (approximately 5-10%). There was a low uptake of [11C]RTI-364 in serotonin-rich brain areas, whereas [11C]RTI-330 and [11C]RTI-357 showed a marked uptake of radioactivity in the thalamus and the brainstem, regions known to contain serotonin transporters. Transient equilibrium was reached at 15 and 40 min for [11C]RTI-330 and [11C]RTI-357, respectively. After pretreatment with citalopram, the ratio of radioactivity in the thalamus and the brainstem to the cerebellum were markedly reduced for [11C]RTI-357 but not for [11C]RTI-330. The results indicate that [11C]RTI-357 is a potential PET radioligand for quantitation of the serotonin reuptake site.