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.

Measurement of striatal D2 dopamine receptor density and affinity with [11C]-raclopride in vivo: a test-retest analysis.

Subacute and long-term stability of measurements of D2 dopamine receptor density (Bmax), affinity (Kd) was studied with positron emission tomography in eight healthy male volunteers. [11C]-Raclopride and the transient equilibrium method were used to measure D2 receptor characteristics. The interval between measurements (scan pairs) was 3 to 7 weeks (subacute) for four subjects and 6 to 11 months (long-term) for four subjects. A test-retest analysis of quantitative measurements of D2 receptor Bmax and Kd was compared with that done on binding potential (BP, Bmax/Kd) measures. In addition, the effect of error in defining the transient equilibrium time (tmax) in the parameter estimation procedure was explored with simulations. The subacute test-retest indicates good reproducibility of D2 receptor density, affinity, and BP ratio measurements with intraclass correlation coefficients of 0.90, 0.96, and 0.86, respectively. The variability of the measurements after 6 to 11 months was slightly higher than that seen in a subacute testing for Kd and more clearly so for binding potential and Bmax. The absolute variability in Bmax (14.5%) measurements was consistently higher than that of Kd (8.4%) or BP (7.9%) both in subacute and long-term measurements. Simulations indicated that the Bmax and Kd estimation procedure is more sensitive to error in the tmax than that for the BP. The results indicate a good overall stability of the equilibrium method with [11C]raclopride for measuring dopamine D2 receptor binding characteristics in the striatum. The BP approach is more stable than Kd and especially Bmax measurements. Error in defining the tmax in particular in the low specific radioactivity scan may be one source of greater variability in Bmax versus BP. However, a higher intraindividual variability in measurements of the D2 receptor Bmax also may include a component of continuous regulation of this parameter over time. These methodologic aspects should be considered in the design and interpretation of longitudinal studies on D2 dopamine receptor characteristics with [11C]-raclopride.

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.

Myocardial efficiency during calcium sensitization with levosimendan: a noninvasive study with positron emission tomography and echocardiography in healthy volunteers.

Dynamic positron emission tomography (PET) with [11C]acetate allows noninvasive assessment of myocardial oxygen consumption. In combination with echocardiography, PET enables determination of cardiac efficiency (defined as useful cardiac work per unit of oxygen consumption). We used this approach to compare the effects of levosimendan, a Ca(2+)-dependent calcium sensitizer, with dobutamine and sodium nitroprusside in healthy male volunteers. The effects of levosimendan on k(mono), an index of oxygen consumption, and cardiac efficiency were neutral, whereas the hemodynamic profile was consistent with balanced inotropism and vasodilatation. Dobutamine enhanced cardiac efficiency at the expense of increased oxygen requirement, but the effects of nitroprusside on k(mono) and cardiac efficiency were neutral. This study shows the feasibility of PET in phase 1 pharmacodynamic studies and suggests potential energetical advantages of calcium sensitization with levosimendan.

Myocardial efficiency during levosimendan infusion in congestive heart failure.

AIMS: Levosimendan, a novel calcium-dependent calcium sensitizer of the myocardial contractile proteins, also enhances diastolic relaxation and induces peripheral vasodilation by opening potassium channels. To assess the combined energetical effects of levosimendan infusion in vivo, we performed positron emission tomography in patients with decompensated chronic heart failure. METHODS AND RESULTS: Eight hospitalized patients with New York Heart Association functional class III or IV heart failure received levosimendan or placebo intravenously in a randomized double-blind cross-over study. During steady-state, dynamic positron emission tomography with [11C]acetate was used to assess myocardial oxygen consumption and [15O]H2O to measure myocardial blood flow. Cardiac performance and dimensions were assessed by pulmonary artery catheterization and echocardiography. Compared with healthy volunteers, myocardial oxygen consumption during placebo was elevated in the right ventricle but comparable in the left ventricle. During administration of levosimendan, cardiac output increased by 32% (P = .002) mainly because of higher stroke volume. Coronary, pulmonary, and systemic vascular resistance values were significantly reduced. Mean myocardial blood flow increased from 0.76 to 1.02 mL/min/g (P = .033). Levosimendan was neutral on myocardial oxygen consumption and left ventricular efficiency, but it improved right ventricular mechanical efficiency by 24% (P = .012). CONCLUSIONS: Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. It enhances cardiac output without oxygen wasting, particularly by improving efficiency in the right ventricle.

Striatal uptake of the dopamine reuptake ligand [11C]beta-CFT is reduced in Alzheimer's disease assessed by positron emission tomography.

Striatal dopamine reuptake sites were studied with PET in Alzheimer's disease (AD). A cocaine analogue, [11C]beta-CFT was used as a radioligand. In patients with AD, the reduction in [11C]beta-CFT uptake was about 20% from the age-adjusted mean value in control subjects, both in the putamen (p = 0.002) and in the caudate nucleus (p = 0.002). Thus, the putamen and the caudate nucleus were equally affected, in contrast to Parkinson's disease, which shows predominantly putaminal reduction. We found that the smaller the [11C]beta-CFT uptake in the putamen or in the caudate nucleus, the more severe the extrapyramidal symptoms. In healthy volunteers (nine women, six men; aged 23 to 70 years), [11C]beta-CFT uptake was reduced with age, both in the putamen (r = -0.70, p < 0.01) and in the caudate nucleus (r = -0.77, p < 0.001). The average decline per decade was 4.4% in the putamen and 4.7% in the caudate nucleus. We conclude that the brain dopaminergic system is affected in AD because the striatal uptake of the dopamine reuptake ligand [11C]beta-CFT is decreased. This reduction in [11C]beta-CFT uptake correlates with the severity of the extrapyramidal symptoms of the patients.

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.

[11 C]Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsy: correlation with hippocampal MR volumetry, T2 relaxometry, and neuropathology.

OBJECTIVE: To detect reduced [11C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology. METHODS: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [11C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model. RESULTS: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis. CONCLUSION: [11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.

Radiotherapy treatment planning and long-term follow-up with [(11)C]methionine PET in patients with low-grade astrocytoma.

PURPOSE: To evaluate the feasibility of [(11)C]-methionine positron emission tomography (MET PET) in radiotherapy (RT) treatment planning and long-term follow-up in patients with low-grade glioma. PATIENTS: Thirteen patients with low-grade astrocytoma and 1 with anaplastic astrocytoma underwent sequential MET PET and magnetic resonance imaging (MRI) before and 3, 6, 12, and 21-39 months after RT, respectively. Ten patients were studied after initial debulking surgery or biopsy and 4 in the recurrence phase. METHODS: A total of 58 PET scans were performed. After transmission scanning, a median dose of 425 MBq of MET was injected intravenously and emission data was acquired 20 min after injection for 20 min. The uptake of MET in tumor area was measured as standardized uptake value (SUV) and tumor-to-contralateral brain SUV ratios were generated to assess irradiation effects on tumor metabolism. Functional imaging with PET was compared with concurrent MRI in designing the RT planning volumes and in assessment of response to RT during a median follow-up time of 33 months. RESULTS: In 12 patients (86%), tumor area was clearly discernible in the baseline PET study. In the remaining 2 patients with a suspected residual tumor in MRI, PET showed only a diffuse uptake of MET interpreted as negative in the original tumor area. In the dose planning of RT, MET PET was helpful in outlining the gross tumor volume in 3 of 11 cases (27%), whereas PET findings either coincided with MRI (46%) or were less distinctive (27%) in other cases. In quantitative evaluation, patients with a low tumor SUV initially had significantly better prognosis than those with a high SUV. Tumor-to-contralateral brain uptake ratios of MET discriminated well patients remaining clinically stable from those who have since relapsed or died of disease. CONCLUSION: Quantitative MET PET has prognostic value at the time of initial treatment planning of low-grade glioma. Some patients may benefit of RT volume definition with MET PET, which seems to disclose residual tumor better than MRI in selected cases. Stable or decreasing uptake of MET in tumor area after RT during follow-up seems to be a favorable sign.

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.

Nodal staging of lymphoma with whole-body PET: comparison of.

UNLABELLED: Accurate staging is elementary for optimal management of malignant lymphoma. Advanced cases may be curable with multidrug chemotherapy combined with radiotherapy, whereas limited disease can sometimes be cured by local radiotherapy only. Recently, FDG imaging with whole-body PET (WB PET) has been introduced as an accurate method for staging lymphoma. We evaluated the usefulness of L-[methyl-11C]methionine (MET) in comparison with FDG as a tracer for nodal staging of lymphoma with WB PET. METHODS: Nineteen patients with untreated, histologically proven malignant lymphoma underwent WB PET imaging with MET and FDG within 1 wk before treatment. Fourteen patients had non-Hodgkin's lymphoma (NHL), and 5 had Hodgkin's disease (HD). Two of these 19 patients were excluded from the final analysis because of hyperglycemia. WB PET images using FDG and MET were visually compared by 3 independent interpreters, and the PET findings were correlated with the data on the basis of conventional staging studies. RESULTS: Fifty-five of 178 lymph node regions were classified as diseased both by FDG PET and by CT, and 54 of 178 were classified as diseased both by MET PET and by CT. In addition, 11 lymph node regions that CT showed to be normal avidly accumulated FDG. Ten of these lymph node regions also had clear uptake of MET. Another 4 and 5 lymph node regions were enlarged at CT but were judged to be normal by FDG and MET PET, respectively. In nodal staging, both FDG PET and MET PET would have upstaged the disease in 3 patients. MET PET would also have downstaged the disease in 1 patient. CONCLUSION: FDG and MET seem to be comparable in the detection of lymphoma by WB PET. However, visual interpretation of the images tends to be hampered more by physiologic accumulations of MET than by normal accumulations of FDG, and MET may be preferable to FDG in hyperglycemic patients undergoing staging studies with PET.

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.

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.

Upregulation of putaminal dopamine D2 receptors in early Parkinson's disease: a comparative PET study with [11C] raclopride and [11C]N-methylspiperone.

UNLABELLED: Dopamine D2 receptor function was assessed in a PET study with 2 dopamine D2 receptor PET ligands, [11C]raclopride (RAC) and [11C]N-methylspiperone (NMSP), in early Parkinson's disease. METHODS: Seven patients with early Parkinson's disease and 5 healthy volunteers were studied. Each underwent PET both with reversible [11C]RAC and with irreversible [11C]NMSP. RESULTS: Upregulation of dopamine D2 receptors in the putamen contralateral to the predominant symptoms of Parkinson's disease was confirmed using both [11C]RAC and [11C]NMSP. Uptake of [11C]RAC in the contralateral putamen was 105% of uptake in the opposite putamen (P = 0.020). For [11C]NMSP, uptake in the contralateral putamen was 105% of uptake in the ipsilateral putamen (P = 0.011). No significant differences between Parkinson's disease patients and healthy volunteers were detected in any of the studied brain regions using either [11C]RAC or [11C]NMSP. No significant differences between [11C]RAC and [11C]NMSP uptake were detected in the striatum, whereas in the extrastriatal regions, [11C]NMSP showed significantly higher uptake than [11C]RAC both in healthy volunteers and in Parkinson's disease patients. CONCLUSION: This study confirms an increase in dopamine D2 receptors in the putamen contralateral to the predominant symptoms, compared with the ipsilateral putamen, in early Parkinson's disease. This increase was seen both with reversible ligand [11C]RAC and with irreversible ligand [11C]NMSP and thus does not seem a consequence of depleted endogenous dopamine.

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.

PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease.

UNLABELLED: The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/- 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains.

PET studies on dopamine D1 receptors in the human brain with carbon-11-SCH 39166 and carbon-11-NNC 756.

UNLABELLED: PET studies were carried out on brain dopamine D1 receptors using two new ligands, [11C]SCH 39166 and [11C]NNC 756. METHODS: Four normal subjects and eight predominantly unilateral patients with early Parkinson's disease were investigated. Each of them underwent both a PET scan with [11C]SCH 39166 and one with [11C]NNC 756. A dose of about 185 MBq (5 mCi) of these ligands was administered intravenously and a dynamic PET scan with an ECAT 931/08 PET camera was carried out. Ratios between the striatal and cerebellar uptake of these compounds were calculated. RESULTS: Both [11C]SCH 39166 and [11C]NNC 756 accumulated in the striatum. There was also some neocortical binding; 75% of the striatal value in the case of [11C]SCH 39166 and 60% with [11C]NNC 756 which displayed higher (p < 0.01) uptake in the striatum than [11C]SCH 39166. There were no significant side-to-side differences in the controls nor in the parkinsonian patients. CONCLUSIONS: These results imply that both [11C]SCH 39166 and [11C]NNC 756 can be used in PET studies for the visualization and quantification of dopamine D1 receptors. Since [11C]NNC 756 has a significantly better signal-to-noise ratio in the striatum than [11C]SCH 39166, it seems to offer definite advantages for studies of D1 receptors.

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.

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.

Transport of carbon-11-methionine is enhanced by insulin.

UNLABELLED: The anabolic effects of insulin are not restricted to carbohydrate and lipid metabolism but also include protein metabolism. However, the effects of insulin on protein metabolism have been difficult to demonstrate in vivo. Amino acid transport is partly regulated by insulin according to the experimental data. PET provides a way to measure fractional uptake rates of amino acids. The purpose of this study was to measure the effect of insulin on amino acid transport from the plasma to the human parotid glands. METHODS: We compared the uptake of L-[methyl-11C]methionine ([11C]methionine) into the parotid glands and cerebellum in seven healthy volunteers during the fasting state and euglycemic insulin clamp technique (1 mU/kg per minute). RESULTS: The fractional uptake rate of [11C]methionine was increased by 31% for the right parotid gland (p = 0.003) and by 29% for the left parotid gland (p = 0.009) during insulin clamp, while the increase was 19% for the cerebellum (p = 0.01). The concentration of amino acids typical for the hormone-sensitive transport system A was 11% lower during insulin infusion than in the fasting state. CONCLUSION: The uptake of methionine into brain tissue does not seem to be under major control by insulin, while the transport of methionine in the parotid glands is stimulated by insulin. PET provides a sophisticated method to study the transport system of amino acids in vivo.