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K Någren

Publications and source records attributed to K Någren.

At least 55 records · Page 3Linked to original sources
PubMed1996

Serotonergic modulation of striatal D2 dopamine receptor binding in humans measured with positron emission tomography.

The modulating effect of serotonergic drugs on the striatal dopamine neurotransmission has remained controversial, and there are no published data on serotonin-dopamine interaction obtained from living human brain. Citalopram is a selective serotonin reuptake inhibitor widely used in the treatment of depression (20-40 mg/day). We measured the effects of acute (20 mg, per os) and chronic (20 mg/day for 14 days) doses of citalopram and placebo intake on [11C]-raclopride binding to striatal D2-receptors in eight healthy volunteers by using positron emission tomography. Although the effect magnitude was not large, the results indicate that chronic citalopram intake slightly decreases the raclopride binding which may reflect increased dopamine release in the striatum. In addition, after 14 days there was a high correlation between the citalopam plasma levels and the decrease in the [11C]-raclopride binding in both the caudate and the putamen, although statistically significant effect in the raclopride binding potential was more pronounced in the putamen. This report suggests functional interaction of brain dopaminergic and serotonergic systems in vivo in man.

Adult↗
PubMed1996

Effects of cocaine on [11C]norepinephrine and [11C] beta-CIT uptake in the primate peripheral organs measured by PET.

The toxic properties of cocaine are related to both the central and peripheral effects. To identify possible lethal mechanisms and the accumulation of cocaine in various organs, the effects of cocaine on [11C]norepinephrine and cocaine congener [11C] beta-CIT uptake in Cynomolgus monkeys were measured by positron emission tomography (PET). Cocaine (5 mg/kg) noticeably inhibited [11C]norepinephrine uptake in the heart. The uptake of [11C] beta-CIT in the heart and lung was reduced by pretreatment with cocaine. There was a significant uptake in the liver which was increased following cocaine pretreatment. The results of this study confirm that cocaine blocks the neuronal uptake of norepinephrine in sympathetic nerve terminals in the myocardium. The effect of cocaine on [11C] beta-CIT uptake indicates that the binding sites in the heart and lung are saturable, while the uptake mechanism in the liver is different from those of the heart and lung.

Animals↗
PubMed1996

[11C]metaraminol, a false neurotransmitter: preparation, metabolite studies and positron emission tomography examination in monkey.

No-carrier-added racemic [11C]metaraminol was prepared by a selective condensation of [11C]nitroethane with 3-hydroxy-benzaldehyde using tetrabutylammonium fluoride in tetrahydrofuran (THF) as a catalyst, followed by a reduction with Raney nickel in formic acid. [11C]Metaraminol was produced in 30 to 45% decay-corrected yield from [11C]nitroethane (13 to 20% decay corrected from [11C]CO2) within 45 to 55 min total synthesis time. Reversed phase high-performance liquid chromatography (HPLC) was used for the separation of the racemic erythro- and threo-forms of [11C]metaraminol. The radiochemical purity was higher than 98%, and the specific radioactivity at the end of synthesis was 500 to 800 Ci/mmol (18 to 30 GBq/mumol). Positron emission tomography (PET) examination of racemic erythro-[11C]metaraminol in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. Following pretreatment with the selective norepinephrine reuptake inhibitor desipramine, the radioactivity uptake in the myocardium was markedly reduced (80%), demonstrating the specificity of erythro-[11C]metaraminol for the norepinephrine reuptake system of the heart. Pretreatment with desipramine had no effect on radioactivity in lung. The metabolism was rapid for [11C]metaraminol. The amounts of the total radioactivity representing [11C]metaraminol in plasma, determined by HPLC, were 14% at 6 min and 8% at 34 min. The high specific uptake of racemic erythro-[11C]metaraminol indicates that enantiomerically pure (R,S)-[11C]metaraminol has potential for detailed mapping of the sympathetic innervation of the human myocardium.

Animals↗
PubMed1996

Striatal dopamine D1 receptors in narcolepsy: a PET study with [11C]NNC 756.

We investigated dopamine D1 receptors in the putamen and caudate nucleus with positron emission tomography in six patients with narcolepsy and five healthy controls using [11C]NNC 756 as ligand. The caudate-to-cerebellum and putamen-to-cerebellum ratios of [11C]NNC 756 were within normal limits in patients with narcolepsy. No evidence of increased D1 receptor binding in narcolepsy was found.

Adult↗
PubMed1995

Evaluation of response to radiotherapy in head and neck cancer by positron emission tomography and [11C]methionine.

PURPOSE: To evaluate the usefulness of positron emission tomography (PET) and L-[methyl-11C]methionine in assessing treatment response to radiotherapy in head and neck cancer. METHODS AND MATERIALS: Fifteen patients with head and neck cancer (13 with squamous cell carcinoma, 1 with adenocystic carcinoma, and 1 with paranasal plasmocytoma) underwent a PET study with [11C]-methionine both before and after preoperative radiotherapy to the total tumor dose of 61-73 Gy. Twelve primary and 12 metastatic tumor sites were within the field of view. Nineteen of the 24 tumor sites were surgically explored after radiotherapy, and the tumor standardized uptake values (SUVs) of [11C]methionine were compared with histological findings. RESULTS: All 24 malignant lesions were detectable in the pretreatment study. In all but one case, the tumor SUV decreased after radiotherapy. The median SUV of the tumor site was smaller (1.9, range, 1.3-3.1, n = 7) in cases with histologically verified complete response than in cases with persistent cancer (median 4.1, range, 2.8-7.6, n = 12, p = 0.0008). A complete histological response was verified in none of the 9 cases with a postirradiation SUV larger than the median (3.1), whereas 7 of the 10 cases with a SUV of 3.1 or smaller had complete response (p = 0.003). The preirradiation uptake of [11C]methionine in tumors did not have significant association with histological response (p = 0.45). The PET findings correlated well with follow-up data in five cases with unoperated tumor sites. The [11C]methionine uptake of the submandibular salivary glands decreased after radiotherapy (p = 0.04). CONCLUSION: PET with [11C]methionine as a tracer may be useful in assessing response to radiotherapy in head and neck cancer. High uptake of [11C]methionine in the postirradiation scan suggests the presence of persistent disease.

Adult↗
PubMed1995

PET examination of the monoamine transporter with [11C]beta-CIT and [11C]beta-CFT in early Parkinson's disease.

The monoamine transporter was studied in 4 healthy controls and 5 patients with early Parkinson's disease (PD), who had not received any antiparkinsonian medication, by means of positron emission tomography (PET) using two novel ligands, [11C]beta-CIT and [11C]beta-CFT. Both ligands showed highest uptake in the striatum. There was intermediate accumulation of activity in the thalamus and midbrain, which was more marked for [11C]beta-CIT than for [11C]beta-CFT. In the cortical areas, uptake of both ligands was not different from that seen in the cerebellum. In the controls, the putamen-to-cerebellum and caudate-to-cerebellum ratios for [11C]beta-CFT were higher than those for [11C]beta-CIT (putamen: 3.15 +/- 0.39 for [11C]beta-CFT, and 1.84 +/- 0.10 for [11C]beta-CIT; caudate: 3.15 +/- 0.31 for [11C]beta-CFT, and 1.95 +/- 0.17 for [11C]beta-CIT). Reduction from mean control value in PD patients was greater for [11C]beta-CFT (45% in the putamen contralateral to the predominant symptoms, P < 0.001) than for [11C]beta-CIT (20%, P > 0.05). [11C]beta-CFT uptake in the caudate nucleus was also diminished in PD patients (to 80% of the control mean, P < 0.05), whereas [11C]beta-CIT was within normal range (reduced to 90% of the control mean). These results indicate that both [11C]beta-CIT and [11C]beta-CFT are useful PET ligands to study brain monoamine transporter in healthy controls and in patients with PD. However, [11C]beta-CFT seems superior to [11C]beta-CIT in this respect.

Adult↗
PubMed1995

Increased density of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease: a PET study with [11C]raclopride.

Striatal dopamine D2 receptors were studied, using positron emission tomography (PET), in 10 patients with early Parkinson's disease without any antiparkinsonian medication and in 14 healthy controls. [11C]Raclopride was used as ligand and an equilibrium method was applied. The maximum count of receptors (Bmax) and their dissociation constant (Kd) were calculated according to the Scatchard principle. In parkinsonian patients, the Bmax of D2 receptors was increased in the putamen contralateral to the predominant symptoms, as compared to the opposite putamen, by 33% (p = 0.0008). In the caudate nucleus no significant side to side differences was noted. On comparison with age-matched healthy controls, Bmax values in the putamen (p = 0.0012) but not in the caudate nucleus contralateral to the side of predominant clinical symptoms were increased in PD patients. The Kd values were unchanged. The difference in putaminal Bmax values between the opposite hemispheres correlated with the difference in the severity of parkinsonian motor symptoms between the two body sides (r = 0.69, p = 0.03). The present results show that there is both a relative and absolute increase in the number of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease.

Carbon Radioisotopes↗
PubMed1995

Improved synthesis of some commonly used PET radioligands by the use of [11C]methyl triflate.

[11C]Methyl triflate was compared with [11C]methyl iodide as a labelled precursor in the synthesis of some commonly used PET radioligands, L-[11C]deprenyl, [11C]m-hydroxyephedrine (MHED), [11C] beta-CIT, [11C] beta-CFT and [11C]SCH 39166 which have been prepared previously in comparatively low yields from [11C]methyl iodide. A new dopamine reuptake radioligand, [11C] alpha-CIT, was also prepared. The results demonstrate that higher yields are obtained with shorter reaction times, lower reaction temperatures and smaller amounts of precursors with [11C]methyl triflate.

Benzazepines↗
PubMed1995

Positron emission tomography study of human narcolepsy: no increase in striatal dopamine D2 receptors.

We investigated dopamine D2 receptors in the caudate nucleus and putamen with positron emission tomography in seven patients with narcolepsy and seven healthy controls by using [11C]raclopride as a ligand. We applied an equilibrium method and Scatchard principle to give a quantitative estimation of the number (Bmax) and dissociation constant (Kd) of the receptors. Both the Bmax and Kd were within the normal range in the caudate nucleus and putamen in narcoleptic patients. We found no evidence for increased D2 receptor binding in narcolepsy.

Adolescent↗
PubMed1995

Carbon-11-methionine PET imaging of malignant melanoma.

UNLABELLED: The purpose of the study was to assess the feasibility of PET and L-[methyl-11C]methionine (11C-methionine) in the detection of malignant melanoma. METHODS: Ten patients diagnosed with malignant melanoma (two with primary melanoma and eight with metastatic melanoma of the skin) but had no liver metastases underwent a PET study before starting cancer therapy. Dynamic scanning was performed for 40 min in seven patients and 10-20 min in three patients 25-45 min postinjection. RESULTS: Carbon-11-methionine PET detected all melanoma lesions greater than 1.5 cm (n = 22) in diameter, whereas five smaller pulmonary lesions were not detected. The average standardized uptake value of the untreated lesions was 6.3 +/- 2.1 (n = 19) and the uptake rate (influx constant) was 0.085 +/- 0.041 min-1 (n = 16). CONCLUSION: PET imaging with 11C-methionine is an effective method for visualizing melanoma. It may also be useful in measuring tumor metabolic activity in vivo.

Adult↗
PubMed1995

Metabolic imaging of ovarian tumors with carbon-11-methionine: a PET study.

UNLABELLED: This study examines the potential of 11C-methionine as a PET tracer in metabolic imaging of benign and malignant ovarian tumors. METHODS: Four patients with one or two benign ovarian tumors (endometriomas or cystadenomas), two patients with a tumor of borderline malignancy and seven patients with ovarian cancer were studied with 11C-methionine and PET before laparotomy. CT or MRI were performed as a reference. Tracer uptake was quantitated by calculating tracer standardized uptake values (SUVs) and the kinetic influx constants (Ki values). RESULTS: Benign or borderline malignant tumors did not accumulate 11C-methionine, whereas all carcinomas had significant uptake. The mean SUV of the primary carcinomas was 7.0 (s.d., 2.2) and the mean Ki was 0.14 min-1 (s.d., 0.1 min-1), but the distribution of tracer uptake was highly heterogenous in four of six tumors. CONCLUSION: Ovarian cancer can be imaged with 11C-methionine and PET. This method also may be of value in the differential diagnosis between benign and malignant ovarian neoplasms. Due to physiological accumulations and methodological limitations, the value of 11C-methionine PET in the staging of ovarian cancer appears to be limited.

Adenocarcinoma, Clear Cell↗
PubMed1994

Striatal D2 dopamine receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography.

BACKGROUND: According to the D2 dopamine receptor hypothesis of schizophrenia, there is an increased number of D2 receptors in the brains of schizophrenic patients than in those of healthy controls. We tested this hypothesis in 13 newly admitted neuroleptic-naive schizophrenic patients and 10 healthy volunteers using positron emission tomography. METHOD: The quantification of striatal D2 dopamine receptor density (Bmax) and affinity (Kd) was done using an equilibrium model described for raclopride labeled with carbon 11. RESULTS: No statistically significant alterations were found in D2 receptor densities or affinities between the patient and control groups. However, a subgroup of four patients with a relatively high striatal D2 dopamine density was identified. Two patients, especially, had D2 dopamine densities almost twice as high as the mean control Bmax value. The Kd values also tended to be higher in this subset of patients than in the controls. No consistent striatal D2 dopamine receptor laterality was observed in schizophrenic patients or controls. However, an association of high D2 dopamine density in the left striatum and the mass of raclopride injected in the scan with low-specific radioactivity was observed in patients but not in controls. CONCLUSIONS: There are no general changes in D2 dopamine receptor Bmax or Kd values in neuroleptic-naive schizophrenics, but there may be a subgroup of patients with aberrant striatal D2 dopamine receptor characteristics in vivo.

Adult↗
PubMed1994

Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart.

(-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [11C]norepinephrine indicates that enantiomerically pure (-)-[11C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium.

Animals↗
PubMed1994

Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence.

Striatal D2 dopamine receptor characteristics of nine male patients with alcohol dependence abstinent for 1-68 weeks and eight healthy male volunteers were studied in vivo with positron emission tomography. The selective D2 receptor ligand [11C]raclopride and equilibrium model was used for D2 receptor density (Bmax) and affinity (Kd) measurements. A trend for a decreased striatal D2 receptor density and for reduced D2 receptor affinity was observed in patients with alcohol dependence. These parameters were not statistically significantly different between alcoholics and controls, but the ratio between D2 receptor density and affinity (Bmax/Kd or the striatum/cerebellum ratio from the high specific activity scan) was highly significantly lower in alcoholics than that of controls. In conclusion, the low D2 dopamine receptor Bmax/Kd ratio (striatum/cerebellum ratio) indicates that specific aspects of striatal [11C]raclopride binding in vivo are deviant in alcoholics compared to controls. The result is compatible with a reduced avidity of striatal dopamine D2 receptors in alcoholics, which is in line with the idea that D2 dopaminergic mechanisms are involved in the biology of alcohol dependence in man.

Adult↗