Biomedical subjects

K Någren

Publications and source records attributed to K Någren.

At least 73 records · Page 4Linked to original sources

PubMed1994

Selective synthesis of racemic 1-11C-labelled norepinephrine, octopamine, norphenylephrine and phenylethanolamine using [11C]nitromethane.

A new and simple method for the selective condensation of no-carrier-added [11C]nitromethane (1) with various substituted (protected) benzaldehydes to [beta-11C]beta-nitrophenethyl alcohols was developed. This method which utilizes tetrabutylammonium fluoride in THF as a catalyst gave a condensation yield of 80-90% and a selectivity of 80-90% for [11C]nitroalcohol vs [11C]nitrostyrene formation within 2 min. Reduction of these [11C]nitroalcohols with Raney nickel in formic acid gave the corresponding [11C]aminoalcohols in a yield of 60-90%. Boron tribromide was used for the cleavage of 4-methoxy and 3,4-(methylenedioxy) phenol protecting groups. After HPLC-purification, racemic 1-11C-labelled norepinephrine (7), phenylethanolamine (4), norphenylephrine (5) and octopamine (6) were prepared in a 12-30% decay corrected total radiochemical yield (20-50% counted from 1) with an overall synthesis time of 40-70 min from end of bombardment (EOB). The radiochemical purity was > 98% and the specific radioactivity 700-1500 Ci/mmol (26-56 GBq/mumol).

2-Hydroxyphenethylamine↗

PubMed1994

Head and neck cancer: effect of food ingestion on uptake of C-11 methionine.

PURPOSE: To determine the influence of a standardized meal on tumor uptake measured with positron emission tomography (PET) and L-(methyl-carbon-11) methionine. MATERIALS AND METHODS: Five patients with untreated squamous cell cancer of the head and neck underwent PET, first in a fasting state and then 6-7 days later after ingesting a liquid meal. RESULTS: All tumors were seen on PET scans, and image quality remained good after food ingestion. The standardized uptake values of the tumors were 3.7-11.4 in the fasting state but decreased after the meal (range, 3.3-10.0; P < .04). No substantial change was measured in tumor C-11 methionine influx constants (Ki values). CONCLUSION: Although cancer imaging with PET and C-11 methionine can be performed even in the patient has not fasted, a standardized meal may decrease tumor C-11 methionine uptake.

Aged↗

PubMed1994

Imaging of uterine carcinoma by carbon-11-methionine and PET.

UNLABELLED: L-[methyl-11C]methionine ([11C]methionine) is probably one of the most useful positron-emitting tracers for metabolic imaging of human cancer. In this study, we investigated whether human uterine cancer can be imaged with [11C]methionine and PET. METHODS: Fourteen patients with primary uterine malignancy participated in the study. Eight patients had endometrial carcinoma and six had cervical carcinoma. The normal endometrium was analyzed in four additional patients with no uterine malignancy and in one patient with cervical cancer. Tracer uptake was quantitated by calculating both the standardized uptake values (SUVs) and the kinetic influx constants (Ki values) for the tracer. RESULTS: All patients with either cervical or endometrial carcinoma had increased uptake of [11C]methionine in the PET image. The mean SUV of the carcinomas was 8.4 (n = 13; s.d., 1.5) and the mean Ki was 0.15 min-1 (n = 12; s.d., 0.08 min-1), whereas the mean SUV of the normal endometrium was only 4.6 (n = 5; s.d., 0.8). Histologically poorly (Grade III) or moderately (Grade II) differentiated endometrial carcinomas accumulated more [11C]methionine than the well-differentiated (Grade I) ones (p = 0.04 for the SUVs, and p = 0.05 for the Ki values). There were also variable physiological accumulations of [11C]methionine in the pelvis. CONCLUSIONS: Uterine carcinoma accumulated [11C]methionine more than the normal endometrium. However, the physiological accumulations of [11C]methionine in the pelvis may confuse the interpreter of the PET image; thus, morphological imaging also needs to be performed as a reference to localize the tumor accurately. We conclude that human uterine carcinoma can be effectively imaged with [11C]methionine and PET.

Adenocarcinoma↗

PubMed1993

PET study on striatal dopamine D2 receptor changes during the progression of early Parkinson's disease.

[11C]Raclopride uptake to dopamine D2 receptors was investigated with positron emission tomography (PET) in patients with early Parkinson's disease at the time of the diagnosis and after a half-year interval. During this progressive period of the disease, the patients received no antiparkinsonian medication. The upregulation of striatal D2 receptors, which was seen in all patients already at the time of the diagnosis, persisted. Although the patients initially showed unilateral disease, they had developed bilateral symptoms by the time of the second PET scan, but the disease was still asymmetric. The present results show that the relative increase in [11C]raclopride uptake in the striatum contralateral to the symptoms as compared with the opposite striatum will be preserved even during the progression of the disease, provided that the symptoms show clear-cut asymmetry.

Adult↗

PubMed1993

Preparation of [1-11C]dopamine, [1-11C]p-tyramine and [1-11C]m-tyramine. Autoradiography and PET examination of [1-11C]dopamine in primates.

A method for no-carrier-added 1-11C-labelling of 3-hydroxy-, 4-hydroxy- and 3,4-dihydroxy-substituted phenethylamines is described. [11C]Dopamine, [11C]p-tyramine and [11C]m-tyramine were prepared from on-line produced [11C]nitromethane. Condensation of [11C]nitromethane with various protected and unprotected benzaldehydes was investigated. A one-pot two-step reduction of the substituted 11C-labelled nitrostyrene intermediates, gave after hydrolysis and reversed-phase semi-preparative HPLC-purification the corresponding labelled amines in a total radiochemical yield of 8-20% (based on [11C]CO2 and decay-corrected). The total synthesis time was 45-50 min with a specific radioactivity of 400-1000 Ci/mmol (15-37 GBq/mumol). The radiochemical purity was higher than 98% [11C]Dopamine was used for in vitro autoradiography on human post-mortem brain sections and for positron emission tomography (PET) on Cynomolgus monkeys. Autoradiographic examination of [11C]dopamine binding on human brain section post-mortem demonstrated specific binding in the caudate putamen and the substantia nigra, regions with a dense dopaminergic innervation. Some binding was also seen in the globus pallidum, nucleus ventralis of the thalamus and in nucleus dentatus of the cerebellum, regions where the dopaminergic innervation is very low. In PET examinations of [11C]dopamine binding in Cynomolgus monkeys there was a high uptake of radioactivity in the pituitary, the kidneys and the heart. Any passage of [11C]dopamine across the blood-brain barrier could not be demonstrated. In human PET studies [11C]dopamine has potential as a radioligand for examination of the myocardium, pituitary and kidneys.

Animals↗

PubMed1993

Carbon-11-methionine and PET in evaluation of treatment response of breast cancer.

Uptake of L-methyl-11C-methionine (11C-methionine) in breast cancer metastases was studied with positron emission tomography (PET). Eight patients with soft tissue metastases were studied twice: before the onset of chemotherapy (4), hormonal therapy (3) or radiotherapy (1) and 3-14 weeks later. The radioactivity concentration of the low molecular weight fraction of venous plasma samples separated by fast gel filtration was used as input function. The input corrected uptake rate of 11C-methionine (Ki) in breast cancer metastases before the treatment ranged between 0.035 and 0.186 1 min-1 and the standardised uptake value (SUV) between 2.0 and 11.4. The uptake of 11C-methionine into the metastases decreased when clinical objective stability or regression of the metastases was later obtained and increased in cases where progressive disease was seen during treatment. We conclude that metabolic changes in the amino acid metabolism detected by PET precede the clinical response, and may be of clinical value in predicting the treatment response.

Aged↗

PubMed1993

Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride.

The effect of age on human striatal dopamine D2 receptors was investigated with positron emission tomography (PET) using [11C]raclopride as a radioligand. Twenty-one healthy volunteers aged from 20 to 81 years were studied. An equilibrium method was applied and two separate PET scans with different specific activities of [11C]raclopride were performed. The maximal number of receptors (Bmax) and their dissociation constant (Kd) were calculated using Scatchard analysis. There was an age-dependent decline in the Bmax (r = -0.49; p = 0.02) of striatal D2 receptors while the Kd remained unchanged. The results show that there is an age-related loss of striatal D2 receptors, which, together with other changes in the brain nigrostriatal dopaminergic system, may contribute to extrapyramidal symptoms associated with aging.

Adult↗

PubMed1993

Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine in head and neck cancer.

The positron emission tomography (PET) tracer 2-18F-fluoro-2-deoxy-D-glucose (FDG) is the most widely used tracer in oncology. PET tracer. Another radiotracer, L-methyl-11C-Methionine (11C-methionine), also has been used successfully for PET imaging of brain and lung tumors, non-Hodgkin's lymphoma, breast cancer and head and neck cancer. This study compared FDG and 11C-methionine as tumor-detecting agents in head and neck cancer. Prior to cancer therapy, fourteen patients underwent a PET study with FDG and one with 11C-methionine. Nineteen of 21 malignant lesions that could be evaluated were visible with both tracers. Tracer uptake was measured as standardized uptake values (SUV) and Ki values according to Patlak et al. The mean SUV in FDG studies was 7.7 +/- 4.2 and in 11C-methionine studies 7.7 +/- 2.5, whereas the Ki values in 11C-methionine studies (mean, 0.128 +/- 0.068 min-1) were always higher than in FDG studies (mean, 0.036 +/- 0.023 min-1). A good correlation was found between the SUVs (r = 0.79, p < 0.0001) and the Ki values (r = 0.82, p < 0.001) between the two tracers. Both FDG and 11C-methionine are effective in PET imaging of head and neck cancer, and the uptake rates of the tracers seem to be closely related.

Adult↗

PubMed1992

PET radioligands for dopamine receptors and re-uptake sites: chemistry and biochemistry.

This report, based on the past experience of European centres, offers practical guidance on the chemistry and biochemistry of PET radioligands used for the in vivo imaging of dopamine receptors and re-uptake sites. It mainly summarizes methods for the preparation of D1 and D2 receptor ligands labelled with positron-emitting radioisotopes. Some of these ligands (11C-labelled SCH23390, raclopride and nomifensine, 18F-labelled butyrophenones, [76Br]bromolisuride), which have been found useful in PET clinical investigations, have been emphasized. This report is intended as an introduction and guideline for new PET-groups who want to start research in the dopaminergic neurotransmission imaging field.

Animals↗

PubMed1992

(S)- and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. Preparation, metabolite studies and in vivo distribution in the human brain using PET.

In order to investigate [11C]nicotine binding and metabolism in the living human brain by PET, routine protocols were developed for the preparation and purification of (S)- and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. (S)- and (R)-[11C]nicotine were prepared by N-methylation with [11C]methyl iodide of the appropriate secondary amine, which was liberated in situ by 2,2,6,6,-tetramethylpiperidine (TMP) from its corresponding biscamsylate-salt. (R/S)-[11C]Cotinine was prepared by N-methylation of the amide precursor using tetrabutylammonium hydroxide as a phase transfer catalyst. Straight-phase semipreparative HPLC was in all purifications found to be superior to reversed-phase since the contamination by the norcompounds was eliminated. Reaction in acetonitrile for both (S)- and (R)-[11C]nicotine (5 min, 130 degrees C) and (R/S)-[11C]cotinine (1 min, 80 degrees C) with subsequent straight-phase HPLC purification resulted in 35-45% radiochemical yield (from EOB and decay-corrected) with a total synthesis time of 30-35 min, a specific radioactivity of 1000-1500 Ci/mmol (37-55 GBq/mumol, EOS) and a radiochemical purity > 99%. The uptake and distribution of these tracers in the human brain was studied in healthy volunteers by PET. The metabolite (R/S)-[11C]cotinine did not cross the blood-brain barrier to any significant degree. The amount of the total radioactivity representing (S)-[11C]nicotine measured in plasma by HPLC was 75% at 4 min and 25% at 50 min.

Brain↗

PubMed1992

Carbon-11-methionine and PET is an effective method to image head and neck cancer.

Methionine metabolism is altered in cancer, and methionine labeled with 11C has been successfully used for imaging of brain, lung, and breast cancer and lymphoma. Uptake of L-[methyl-11C]methionine (11C-methionine) in head and neck cancer of 23 patients was studied with PET. Accumulation of 11C-methionine in the tumors was assessed by two different methods: the influx constant, Ki, and the standardized uptake value (SUV). All 23 cancers accumulated 11C-methionine. The mean Ki was 0.147 +/- 0.070 min-1 and the mean SUV 8.5 +/- 3.5. There was a strong correlation between the two measures of tumor uptake (r = 0.92, p less than 0.0001). There was no correlation between the uptake of 11C-methionine and the histological grade of cancer. Head and neck cancer can thus be effectively imaged with 11C-methionine. Carbon-11-methionine PET imaging may be useful in delineating tumors for therapy planning.

Adult↗

PubMed1991

Uptake of 11C-methionine in breast cancer studied by PET. An association with the size of S-phase fraction.

L-[methyl-11-C]methionine (11C-methionine) uptake of seven primary breast cancers, four soft tissue metastases of breast cancer, and three other breast lesions was studied by positron emission tomography (PET). 11C-methionine accumulation was assessed by calculating the standardised uptake value (SUV). The mean SUV for breast cancer was 8.5 +/- 3.3 (s.d.), while the maximal uptake in the liver was 12.4 +/- 1.6, in the bone marrow 5.8 +/- 0.7, and in the myocardium 3.4 +/- 0.6. All eight malignant tumours larger than 30 mm in diameter accumulated clearly 11C-methionine, whereas none of the three smaller cancers (from 12 to 15 mm in diameter) were visualised. Strong uptake of 11C-methionine was associated with a large S-phase fraction (SPF) measured with flow cytometry (r = 0.77, P = 0.01), and the non-visualised cancers had all a small SPF (less than 5.5%). One benign tumour (an abscess) accumulated slightly 11C-methionine. The results indicate that both primary and metastatic breast cancer can be effectively imaged with 11C-methionine by PET, and that the accumulation of 11C-methionine may correlate with the proliferation rate of breast carcinoma.

Aged↗

PubMed1991