Search PubMed⌕ Search

Biomedical subjects

U Ruotsalainen

Publications and source records attributed to U Ruotsalainen.

At least 73 records · Page 4Linked to original sources

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↗

Enhancement of myocardial [fluorine-18]fluorodeoxyglucose uptake by a nicotinic acid derivative.

UNLABELLED: Recently, the euglycemic hyperinsulinemic clamp technique was shown to give excellent image quality during metabolic steady-state conditions. Acipimox is a new potent nicotinic acid derivative that rapidly reduces serum free fatty acid (FFA) levels by inhibiting lipolysis in peripheral tissue. METHODS: To compare the effects of acipimox administration and insulin clamp on [18F]fluorodeoxyglucose ([18F]FDG) uptake and myocardial glucose utilization, five nondiabetic and seven type II diabetic patients who had had previous myocardial infarctions were studied twice: once during a clamp study and once after the administration of acipimox (2 x 250 mg orally). All patients also underwent resting SPECT perfusion imaging prior to PET scans. RESULTS: The patients tolerated acipimox well. Although fasting plasma glucose levels were higher in diabetic patients (9.2 +/- 3.4 versus 5.5 +/- 0.3 mM, p = 0.03), they were decreased both during clamping and after acipimox; during imaging, no significant differences between the groups and approaches were detected. By visual analysis, the image quality and myocardial [18F]FDG uptake patterns were similar during clamping and after acipimox. Compared with the relative [18F]FDG uptake values obtained during clamping, acipimox yielded similar results in normal, mismatch and scar segments (r = 0.88, p = 0.0001). Similar rMGU values were also obtained during both approaches. CONCLUSION: Thus, PET imaging with [18F]FDG after the administration of acipimox is a simple and feasible method for clinical viability studies both in nondiabetic and diabetic patients. It results in excellent image quality and gives rMGU levels similar to the insulin clamp technique.

Adult↗

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↗

Repeated fluorodeoxyglucose positron emission tomography of the brain in infants with suspected hypoxic-ischaemic brain injury.

Positron emission tomography (PET) permits the study of cerebral metabolism in vivo. We performed repeated PET studies with fluorine-18 fluorodeoxyglucose (FDG) as a tracer to measure cerebral glucose metabolism for estimation of neurological prognosis in infants with suspected hypoxic-ischaemic brain injury. Fourteen infants (gestational age 35.3 +/- 4.67 weeks) were examined during the neonatal period (at age 38.4 +/- 2.7 weeks) and again at the age of 3.5 +/- 0.7 months; one further infant was studied only once at the age of 2.5 months. All children also underwent ultrasound examinations. Electroencephalography and computed tomography or magnetic resonance imaging were performed according to their clinical condition and their neurological development has been followed. FDG accumulated most actively in the subcortical areas (thalami, brainstem and cerebellum) and the sensorimotor cortex during the neonatal period. The repeated PET study showed that the uptake of FDG was markedly high and increased in all brain sections of infants with normal development (n = 11), whereas those with delayed development (n = 4) had significantly lower values (P < or = 0.005).

Brain Ischemia↗

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↗

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↗

Insulin resistance is localized to skeletal but not heart muscle in type 1 diabetes.

To determine the tissue localization of insulin resistance in type 1 diabetic patients, whole body and regional glucose uptake rates were determined under euglycemic hyperinsulinemic conditions. Leg, arm, and heart glucose uptake rates were measured using positron emission tomography-derived 2-deoxy-2-[18F]-fluoro-D-glucose kinetics and the three-compartment model described by Sokoloff et al. (L. Sokoloff, M. Reivich, C. Kennedy, M.C. DesRosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897-916, 1977) in eight type 1 diabetic patients and eight matched normal subjects. Whole body glucose uptake was quantitated by the euglycemic insulin clamp technique. Whole body glucose uptake was approximately 31% lower in the diabetic patients (P < 0.01) than in the normal subjects, thus confirming the presence of whole body insulin resistance. The rate of glucose uptake was approximately 45% lower in leg muscle when measured in the femoral region (55 +/- 7 vs. 102 +/- 13 mumol.kg muscle-1.min-1, diabetic patients vs. normal subjects, P < 0.05) and approximately 27% lower in the arm muscles (66 +/- 4 vs. 90 +/- 13 mumol.kg muscle-1.min-1, respectively, P < 0.05), whereas no difference was observed in heart glucose uptake [789 +/- 80 vs. 763 +/- 58 mumol.kg muscle-1.min-1 not significant (NS)]. Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.93, P < 0.005) and arm muscles (r = 0.66, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). We conclude that insulin resistance in type 1 diabetic patients is localized to skeletal muscle, whereas heart glucose uptake is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Heart and skeletal muscle glucose disposal in type 2 diabetic patients as determined by positron emission tomography.

Myocardial and skeletal muscle glucose uptake was examined in 9 type 2 diabetic patients and 13 control subjects using PET and the insulin clamp technique. All subjects had clinically stable coronary heart disease. To simulate the clinical situation, diabetic patients were kept slightly hyperglycemic during the clamp study. Consequently, there were no differences in skeletal muscle or total body glucose disposal between the two groups. With PET, myocardial glucose uptake was 12-20-fold greater than that in skeletal muscle in both groups. However, in the diabetic patients, myocardial glucose uptake was 39% lower (p < 0.05) than in the control subjects. These data suggest a defect in myocardial glucose utilization in type 2 diabetes and emphasize the need for standardized metabolic conditions in diabetic patients during 18FDG PET imaging.

Coronary Disease↗

The value of quantitative analysis of glucose utilization in detection of myocardial viability by PET.

To study whether absolute quantitation of regional myocardial glucose utilization (rMGU) enhances detection of myocardial viability, 70 nondiabetic patients with prior myocardial infarction and angiographically confirmed coronary artery disease were studied with [18F]FDG PET after oral glucose loading. Forty-eight patients were also revascularized and underwent echocardiography after revascularization to detect wall motion recovery. The rMGU was calculated in eight myocardial segments in each patient and the results were compared to normalized (relative) [18F]FDG uptake values. In normal segments (n = 225), rMGU was 56 +/- 18 mumole/min/100 g (mean +/- s.d.) and relative [18F]FDG uptake 97% +/- 12%. The interindividual variation of rMGU in normal myocardium was greater than the intraindividual variation (s.d. 31% versus 11%). The respective values for relative [18F]FDG uptake were 9% and 10%. Both rMGU and [18F]FDG uptake were significantly reduced in segments with scarring observed visually during bypass surgery (29 +/- 19 mumole/min/100 g and 45% +/- 22%, n = 26). The rMGU and [18F]FDG uptake were higher in segments that recovered after revascularization (53 +/- 17 mumole/min/100/g and 110% +/- 21%, n = 27) than in those that did not (37 +/- 20 mumole/min/100 g and 65% +/- 24%, n = 63). However, due to larger variability of rMGU values, normalized [18F]FDG uptake was superior to rMGU in separating normal and scar segments as well as in predicting wall motion recovery. We conclude that rMGU variability is notable and is caused mainly by variations between patients. Interindividual variation is reduced by normalization, which results in more accurate assessment of myocardial viability. Thus, static imaging and semiquantitative analysis are sufficient for the clinical assessment of myocardial viability.

Coronary Angiography↗

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↗

Influence of the blood glucose concentration on FDG uptake in cancer--a PET study.

Radiolabeled [11F]-2-fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue widely used to study tumor metabolism by means of positron emission tomography (PET). Little is known about the effect of hyperglycemia on FDG uptake and PET imaging of tumors. Five patients with head and neck cancer underwent two PET studies prior to cancer therapy, first in the fasting state and then 2-5 days later after oral glucose loading. FDG uptake was measured with standardized uptake values (SUV) and Ki values according to Patlak et al. The fasting SUVs ranged from 4.1 to 10.9 and Kis from 0.021 min-1 to 0.067 min-1, whereas after loading both the SUVs (range 2.2-5.9, p < 0.02) and Ki values (range 0.006-0.042 min-1, p < 0.05) decreased significantly, and the quality of the PET images became markedly poorer. The FDG metabolic rate (Ki x P-Gluc) remained similar in different plasma glucose concentrations in tumors, but increased clearly in muscles after loading. Therefore, patients entering PET-FDG studies should fast and their blood glucose concentration needs to be taken into account when evaluating FDG accumulation.

Aged↗

Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo.

Positron emission tomography permits noninvasive measurement of regional glucose uptake in vivo in humans. We employed this technique to determine the effect of FFA on glucose uptake in leg, arm, and heart muscles. Six normal men were studied twice under euglycemic hyperinsulinemic (serum insulin approximately 500 pmol/liter) conditions, once during elevation of serum FFA by infusions of heparin and Intralipid (serum FFA 2.0 +/- 0.4 mmol/liter), and once during infusion of saline (serum FFA 0.1 +/- 0.01 mmol/liter). Regional glucose uptake rates were measured using positron emission tomography-derived 18F-fluoro-2-deoxy-D-glucose kinetics and the three-compartment model described by Sokoloff (Sokoloff, L., M. Reivich, C. Kennedy, M. C. Des Rosiers, C. S. Patlak, K. D. Pettigrew, O. Sakurada, and M. Shinohara. 1977. J. Neurochem. 28: 897-916). Elevation of plasma FFA decreased whole body glucose uptake by 31 +/- 2% (1,960 +/- 130 vs. 2,860 +/- 250 mumol/min, P less than 0.01, FFA vs. saline study). This decrease was due to inhibition of glucose uptake in the heart by 30 +/- 8% (150 +/- 33 vs. 200 +/- 28 mumol/min, P less than 0.02), and in skeletal muscles; both when measured in femoral (1,594 +/- 261 vs. 2,272 +/- 328 mumol/min, 25 +/- 13%) and arm muscles (1,617 +/- 411 to 2,305 +/- 517 mumol/min, P less than 0.02, 31 +/- 6%). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.75, P less than 0.005), and arm muscles (r = 0.69, P less than 0.05) but not with glucose uptake in the heart (r = 0.04, NS). These data demonstrate that the glucose-FFA cycle operates in vivo in both heart and skeletal muscles in humans.

Adult↗

[18F]-6-fluorodopa PET scanning in Parkinson's disease after selective COMT inhibition with nitecapone (OR-462).

PET studies were performed to investigate the effects of a new cathechol-O-methyltransferase (COMT) inhibitor, nitecapone (OR-462 [3-(3,4-dihydroxy-5-nitrobenzylidene)- 2,4-pentadione]), on the accumulation of dopamine in the striatum and whether it is able to improve [18F]6-fluorodopa imaging of the brain. Altogether, three patients with Parkinson's disease (PD) and three normal volunteers were examined, first without nitecapone and then with an oral dose of 100 mg of nitecapone 1 hour before the IV injection of 3 mCi of [18F]6-fluorodopa. High-pressure liquid chromatography analysis of arterial plasma samples showed a significant reduction in the metabolic conversion rate from [18F]6-fluorodopa to [18F]3-O-methylfluorodopa after the administration of nitecapone. PET studies showed that nitecapone significantly (p less than 0.05) increased the [18F]6-fluorodopa accumulation in the striatum both in PD patients and normal controls; the magnitude of this increase was 20.0 +/- 5.5% (mean +/- SEM). The ratio of radioactivity in the striatum and arterial plasma was increased 39.0 +/- 5.0% (mean +/- SEM) after the administration of nitecapone. Consequently, the quality of PET images after OR-462 was better, which has implications for future [18F]6-fluorodopa studies. In addition, COMT inhibition may have clinical advantages by improving levodopa treatment in PD.

Adult↗

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↗

Euglycemic hyperinsulinemic clamp and oral glucose load in stimulating myocardial glucose utilization during positron emission tomography.

To enable assessment of myocardial viability, myocardial glucose utilization has commonly been stimulated by oral glucose loading. To compare the effects of glucose loading and insulin and glucose infusion (insulin clamp) on PET fluorodeoxyglucose ([18F]FDG) myocardial scan image quality and regional myocardial glucose utilization rate (rMGU), eight patients with angiographically documented coronary artery disease and previous myocardial Q-wave infarction were studied twice, once during insulin clamp and once 1 hr after oral glucose loading. The rMGU rates were derived by graphic Patlak analysis in 33 normal, 10 scar and 6 "hot spot" myocardial segments. Infusion of insulin and glucose gave stable plasma-glucose and serum-insulin levels during imaging. In contrast, glucose loading caused marked changes in plasma-glucose and insulin concentrations. The image quality was clearly superior and the fractional utilization rates of [18F]FDG were twice as high during insulin clamp than after glucose loading (p less than 0.0001). Due to the higher plasma-glucose levels after glucose loading, the calculated rMGU in normal, scar and hot spot myocardial segments was comparable between the two protocols. The insulin clamp technique makes it possible to adjust and maintain a metabolic steady state during the PET study. It does not alter [18F]FDG uptake patterns in different myocardial areas when compared to the standard glucose loading protocol, but this technique results in superior image quality and permits the use of smaller [18F] FDG patient doses.

Administration, Oral↗

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↗