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4‐Fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide is a full 5‐HT1A agonist with high affinity (pKi=9.3), selectivity and a c log P of 3.045. The corresponding PET radioligand 4‐[18F]fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide was synthesized by nucleophilic aromatic substitution on the nitro precursor. The fluorinating agent K[18F]F/Kryptofix 2.2.2 was both dried (9 min, 700 W) and incorporated in the precursor (5 min, 700 W) using a commercially available microwave oven. In a total synthesis time of 60 min, an overall radiochemical yield of 18% (SD=5, n=7, EOS) was obtained. Radiochemical purity was always higher than 99% and specific activity always higher than 81.4 GBq/µmol (2.2 Ci/µmol). Initial brain uptake in mice was 2.19% ID (5.47% ID/g, 2 min) but decreased rapidly (0.17% ID, 0.45% ID/g (60 min)). During the first 20 min p.i., radioactivity concentration of the brain was significantly higher than that of blood demonstrating good brain entry of the tracer. Copyright © 2004 John Wiley & Sons, Ltd.

The combination of a diagnosis of malignancy and hospitalization, isolation and radioactivity of a radionuclide therapy may have an important effect on the psychological equilibrium of patients and may hamper compliance and acceptability. We performed a psychiatric evaluation in order to study psychopathological manifestations and underlying personality related vulnerabilities. During radioisolation, 48 patients 24 male, 24 female mean age 57.8 years with a malignant n26 or nonmalignant n22 pathology who needed isolation for radionuclide therapy, completed a series of questionnaires in order to assess anxiety Spielberger State and Trait Anxiety Inventory STAI, depression Beck Depression Inventory BDI, hopelessness Beck Hopelessness Scale BHS, personality characteristics Temperament and Character Inventory TCI and coping strategies Utrecht's Coping List UCL. Compared to patients with low state anxiety, patients who experienced a high level of state anxiety showed higher levels of depression t2.10 P0.04 and hopelessness t4.20 P< 0.001. Their personality was characterized by significantly higher scores on harm avoidance t2.78 P0.008 and lower scores on selfdirectedness t3.12 P0.003. Coping strategies were more passive t2.43 P0.02, avoiding t2.15 P0.04 and less well aimed t2.64 P0.01. Surprisingly, the nature of disease malignant versus nonmalignant did not influence these results, nor was there a difference between males and females, age, years of education, having a relationship or not, or the duration of hospitalization. Thus, contrary to what may be expected in isolation with radionuclide therapy, subgroups such as women, elderly, cancer patients or lower educated people do not, a priori,exhibit a higher state anxiety level. Our study shows these levels to be closely related to individual personality traits and coping strategies that are inadequate for the situation. Screening for trait anxiety before admission can be easily done and may guide interventions aimed at increasing patient comfort and acceptability.

There is increasing interest in mapping receptors in vivoby using functional imaging modalities such as single photon emission tomography (SPET) and positron emission tomography (PET). Since SPET is a more accessible functional imaging modality than PET and, overall, it is more economical, radioligands suitable for this technique are in greater demand. Recently, 123I-5-I-R91150, a radioligand with high selectivity and affinity for 5-HT2Areceptors in the brain, was introduced for SPET. This study reports on the whole-body distribution and brain uptake of the selective 123I-5-I-R91150 ligand in four normal dogs. The frontal to cerebellar ratio of uptake in time was determined in three dogs. Time-activity curve of venous blood was determined in one dog. Maximal global brain uptake was found at 10-60 min post-injection. Higher brain uptake was noted in the frontal cortical areas compared to the cerebellum. The frontal-cerebellar ratio reached the highest values at 90-180 min. Reversibility and pharmacological selectivity of ligand binding was demonstrated through displacement and blocking studies with the 5-HT2Areceptor antagonist ketanserin. This study demonstrates that the specific 5-HT2Aiodinated ligand can be used for imaging and semi-quantification of the 5-HT2Areceptors in the canine brain in vivoby using SPET.

Performance on the Verbal Fluency Test, as a measure of the ability of initiating processes, is reduced in depressed suicidal patients. The hampered results in this prefrontal executive task parallel the reduction in prefrontal blood perfusion and metabolism in depressed subjects. A neuropsychological activation study with the verbal fluency paradigm could evaluate a possible blunted increase in perfusion in the prefrontal cortex in depressed suicidal patients. Twenty clinically depressed patients who had recently attempted suicide and 20 healthy volunteers were included in a single photon emission computed tomography (SPECT) split-dose activation study following a verbal fluency paradigm. Statistical parametric mapping was used to determine voxelwise significant changes. Differences in regional cortical activation between the letter fluency and category fluency tasks in attempted suicide patients were found. These patients showed a blunted increase in perfusion in the prefrontal cortex. Methodological restrictions concerning group uniformity, medication bias and subjective effort of the participants are discussed. Our findings indicate a blunted increase in prefrontal blood perfusion as a possible biological reason for reduced drive and loss of initiative in attempted suicide patients.

Inflammatory mechanisms contribute to the pathophysiology of senile dementia of the Alzheimer type (sDAT). Previous studies have shown that 57Co single photon emission computed tomography (SPECT) is able to visualize inflammatory lesions, probably by means of the final common pathway of Ca2homeostasis disturbance in both neuronal degeneration and inflammation. The aims of this study were: (1) to detect 57Co SPECT changes in sDAT patients; (2) to correlate these findings with those of conventional neuroimaging techniques and neuropsychological testing (NPT); and (3) to compare 57Co SPECT findings in sDAT patients with those in other types of dementia. Six patients suffering from probable sDAT were included and compared with four patients suffering from other types of dementia. All patients had a magnetic resonance imaging (MRI) scan, NPT, 57Co and 99mTc-ethyl cysteinate dimer (ECD) SPECT scan. Perfusion SPECT images were semiquantitatively evaluated by comparison with an age-matched normal database, while 57Co SPECT scans were assessed qualitatively. MRI and 99mTc-ECD SPECT scans yielded conclusive results with regard to the exclusion of other pathologies and the confirmation of the diagnosis. Using visual analysis, 57Co SPECT scans were unable to show any regional raised uptake, irrespective of the disorder, depth or extent of the perfusion defects, presence of atrophy on MRI or the results of NPT.

This study investigated the feasibility of brain single photon emission computed tomography (SPECT) functional imaging in a neuropsychological test setting, following a single-day protocol with a split-dose paradigm. The Stroop Color Word Test (SCWT) is an example of a well-documented prefrontal activation task. In a split-dose protocol, ten right-handed healthy volunteers were injected twice with 370 MBq 99Tcm-ethyl cysteinate dimer while performing consecutively both series of card-reading of the SCWT. Images were reconstructed using filtered back-projection and normalized to a standard template in Talairach coordinates. Statistical Parametric Mapping (SPM96) was used to determine voxelwise significant changes. A first activation cluster was found in the left medial prefrontal cortex, consisting of the gyrus cinguli anterior and the gyrus frontalis medius and superior. A second activation cluster included the right gyrus frontalis dorsalis and medius. These findings confirm to a large extent the results of previous functional magnetic resonance imaging, positron emission tomography studies of Stroop-like tasks. The choice and validity of various methodological characteristics of the experimental design leading to these results is critically discussed. It is concluded that brain SPECT activation with the Stroop Color Word Test under standard neuropsychological conditions in healthy volunteers, is both technically and practically feasible.

4-[¹²³I]Iodo-N-{2-[4-(6-trifluoromethyl-2-pyridinyl)-1-piperazinyl]ethyl}benzamide (1. ¹²³I), a potential SPECT 5-HT1A radioligand, was synthesized by electrophilic iododestannylation of the tributyltin derivative with n.c.a. [¹²³I]NaI and chloramine-T under acidic conditions (20 min, ambient temperature). Radiochemical yield averaged around 60 % (sd = 8,n = 22). After HPLC purification, chemical purity was higher than 95 % and radiochemical purity higher than 99 %. Specific activity was always higher than 222 GBq/µmol (6 Ci/µmol). The calculated log P is 4.28. Initial brain uptake in NMRI mice was 1.16 % ID (2 min) and decreased slowly afterwards (0.51 % ID (2 h)). 60 min p.i., the majority of the radioactivity in plasma and brain was present as 1. ¹²³I, respectively 75.15 % and 96.48 %. Copyright © 2001 John Wiley & Sons, Ltd.

[¹¹C]Granisetron, a selective 5-HT3 antagonist, was synthesized by N-alkylation of the desmethyl compound using [¹¹C]methyl iodide as the labelling agent in a total synthesis time of 40 min, including semi-preparative HPLC purification. Approximately 40 mCi (1.5 GBq) of the radioligand was obtained with a specific activity of 200–250 mCi/μmol (7.4–9 GBq/μmol). Chemical (≥96%) and radiochemical purity (≥99%) were determined using analytical HPLC. © 1998 John Wiley & Sons, Ltd.

The absolute measurement of regional cerebral blood flow can be made non-invasively if dynamic scanning is performed immediately following the intravenous injection of 99Tcm-labelled HMPAO or ECD. By application of an elementary one-step kinetic model in which the arterial input curve is estimated from a region of interest over the anterior aortic arch projection, a brain perfusion index (BPI) can be calculated which is correlated to the total hemispheric blood flow. The aim of this study was to assess the variability of the BPI approach as applied to the calculation of cerebral blood flow. For 46 patients (30 men, 16 women) aged 23.7–74.4 years (mean 60.3), we calculated hemispheric BPI factors. For two subgroups of 10 patients chosen at random, several data-processing parameters, including the number of noise suppression steps and the linear slope interval for the Patlak fit, were assessed. To determine the influence of region-of-interest selection and to estimate intra- and inter-observer differences, three independent observers conducted a repeat analysis of all 46 patients. From five patients who underwent the same injection procedure twice, an estimate of intra-subject reproducibility was calculated. Temporal noise reduction of the input data significantly decreased the intra-observer variability. Visual estimation of the linear interval in the Patlak curve is much less reproducible than automatic interval selection; very high interval borders in particular significantly decrease the calculated BPI. The intra-observer coefficients of variation for the BPI were 5.3, 5.6 and 7.9 respectively, corresponding to 2.8, 3.0 and 4.1 when converted to hemispheric CBF. The slight inter-observer differences found could be attributed to differing processing parameters. For the five patients in whom the procedure was repeated, the hemispheric BPI reproducibility index was on average 2.6. Determination of absolute hemispheric blood flow can be performed in a precise manner by means of a dynamic scan during the first 2 min after tracer injection after careful optimization of the processing parameters.

Obsessive Compulsive Disorder (OCD) is a disabling psychiatric disorder with a prevalence of approximately 1–3%. Next to disruptions within the orbitofronto-subcortical loops, regions within the salience network (SN) are related to specific OCD symptoms. Of interest, non-invasive brain stimulation has been documented to modulate SN cortical-subcortical loop disturbances. Therefore medial prefrontal regions (supplementary motor area (SMA), pre-SMA and the dorsomedial prefrontal cortex (dmPFC)) could be promising targets. Because accelerated rTMS (arTMS) has been showing fast clinical responses in depression, we applied arTMS (LF) in OCD patients.