[Diagnosis of lymph node metastasis of head-neck carcinomas].
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Head and Neck Neoplasms↗
Biomedical subjects
W Vaalburg
Publications and source records attributed to W Vaalburg.
[Demonstration of cerebral metabolism using positron emission tomography and magnetic resonance spectroscopy in relation to the pathophysiology of focal cerebral disorders].
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Adult↗
Quantification of an 11C-labelled beta-adrenoceptor ligand, S-(-)CGP 12177, in plasma of humans and rats.
beta-Adrenoceptors in human lungs and heart can be imaged with the radioligand 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3- dihydro-2H-benzimidazol-2-11C-one (CGP 12177, [11C]I). For quantification of receptor density with compartment models by adjustment of rate constants, an 'input function' is required which consists of the integral of the concentration of unmodified ligand in arterial plasma over time. A discrepancy in the literature regarding metabolic stability of [11C]I prompted us to study metabolism in rats by reversed-phase HPLC (RP-HPLC) of trichloroacetic acid extracts of arterial plasma after i.v. injection of [11C]I (> 11.1 TBq/mmol, 11 MBq/kg). Some plasma samples were also directly applied to an internal-surface reversed-phase (ISRP) column. In parallel experiments, tritiated [11C]I was employed and methanol extracts of arterial plasma were analyzed by straight-phase TLC. The three methods were in excellent agreement. Unmodified [11C]I decreased from > 98.5% (3H) or > 99.9% (11C) initially to 57 +/- 7% at 80 min post injection due to formation of two polar metabolites. Using the RP-HPLC method, no metabolism was detectable in humans up to 30 min after injection of [11C]I (1851 MBq). Deproteinization of plasma with acetonitrile resulted in the formation of a radioactive species (artifact) which eluted immediately after the void volume in RP-HPLC and which could be mistakenly interpreted as a metabolite. Plasma protein binding was low (ca. 30%) in both humans and rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Myocardial and pulmonary uptake of S-1'-[18F]fluorocarazolol in intact rats reflects radioligand binding to beta-adrenoceptors.
The biodistribution of S-(-)-4-(2-hydroxy-3-(1'-[18F]fluoroisopropyl)- aminopropoxy)carbazole ([18F]S-fluorocarazolol, a non-selective beta-adrenoceptor antagonist) was studied in rats (60 min after 18F injection when specific binding in peripheral organs was maximal). 18F uptake in brain, erythrocytes, heart and lung appeared to be linked to beta-adrenoceptors. CGP-20712A and ICI-89,406 inhibited 18F uptake in heart (predominantly beta 1-adrenoceptors) more potently than in lungs (predominantly beta 2-adrenoceptors). In contrast, ICI-118,551 and procaterol were more potent in the lungs than in the heart. ICI-118,551 inhibited 18F uptake in cerebellum (predominantly beta 2-adrenoceptors) more potently than in cerebral cortex (predominantly beta 1-adrenoceptors). Stereoselectivity of the in vivo binding was demonstrated since S-(-)-propranolol inhibited uptake in target tissues more effectively than R-(+)-propranolol. Myocardial and cerebral imaging may be hampered by poor heart-to-lung contrast and low signal-to-noise ratios, but [18F]S-fluorocarazolol seems suitable for positron emission tomography (PET) of pulmonary beta-adrenoceptors.
Adrenergic beta-Antagonists↗
Localised proton spectroscopy and spectroscopic imaging in cerebral gliomas, with comparison to positron emission tomography.
In 32 patients with gliomas, one- and two-dimensional proton magnetic resonance spectroscopy (1H-MRS) has been conducted, the latter allowing reconstruction of spectroscopic data into a spectroscopic image (MRSI), showing the distribution of the various metabolite concentrations over the cross-sectional plane. For lack of absolute concentrations, the measured concentrations of phosphocholine (CHOL), N-acetyl-L-aspartate (NAA), and lactate (LAC) were conventionally expressed in ratios relative to that of creatine (CREAT). Compared to normal brain tissue, an increased CHOL/CREAT ratio was found in all groups of tumours, in glioblastomas, high-, middle- and low-grade astrocytomas both at the margin and the core of the tumours, but in oligodendrogliomas only at the margin. This is consistent with an increased phosphocholine turnover in relation to membrane biosynthesis by the proliferating cells. The NAA/CREAT ratio was decreased in all groups of tumours, both in the centre and at the margin, reflecting replacement of functioning neurons by neoplastic cells. The LAC/CREAT ratio was elevated in the core of malignant gliomas, which may be the result of a prevailing glycolysis, characteristic of tumours, possibly in conjunction with hypoxia/ischaemia. In the perifocal oedema, there was neither elevation of the CHOL/CREAT ratio nor decrease of the NAA/CREAT ratio; an increased LAC/CREAT ratio therefore rather reflected ischaemia/hypoxia probably due to locally elevated pressure and compromised regional perfusion. In the normal brain, the metabolite ratios of grey matter did not differ from those of white matter. The frontal lobe and basal ganglia showed lower NAA/CREAT ratios than the other cerebral areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Aspartic Acid↗
Brain tumors: L-[1-C-11]tyrosine PET for visualization and quantification of protein synthesis rate.
PURPOSE: Positron emission tomography (PET) with the amino acid tracer L-[1-C-11]-tyrosine was evaluated in 27 patients with primary and recurrent brain tumors. MATERIALS AND METHODS: Patients underwent either static (n = 14) or dynamic PET (n = 13), with quantification of protein synthesis rate (PSR) and tumor-to-background ratio. Findings were compared with histologic findings. RESULTS: Primary brain tumor was proved in 22 patients histologically, as well as metastatic cancer of unknown origin, primary non-Hodgkin lymphoma, meningioma, atypical infarction, and vasculitis in one patient each. At PET, 20 of 22 primary tumors, the metastasis, and non-Hodgkin lymphoma were correctly depicted. A false-positive finding was obtained with the infarction, and the meningioma and vasculitis were not depicted. The calculated sensitivity was 92%; specificity, 67%; and accuracy, 89%. There were no statistically significant relationships between histologic findings, PSR, and tumor-to-background ratio. CONCLUSION: L-[1-C-11]-tyrosine is a valid tracer for diagnosis of brain tumors and allowed quantification of PSR.
Adult↗
N-[18F]-fluoroalkylation of noraporphines: microwave versus thermal treatment.
A comparable study of microwave versus thermal heating is described for the N-[18F]-fluoroalkylation of noraporphines. As compared to thermal treatment, different products were obtained during microwave treatment. Thermal treatment resulted in the loss of the protection of the catechol functionality of the noraporphines (O-deacylation), whereas during microwave treatment N-[18F]-fluoroalkylation was observed. The results described in this report might suggest that the influence of microwaves on chemical transformations is not exclusively thermal.
Alkylation↗
Posterolateral defect of the normal human heart investigated with nitrogen-13-ammonia and dynamic PET.
UNLABELLED: The posterolateral defect is a common artifact seen when static 13N-ammonia imaging with PET is used to assess myocardial perfusion. The aim of this study was to compare dynamic and static. 13N-ammonia PET and to obtain more insight into the cause of the posterolateral defect. METHODS: Dynamic 13N-ammonia PET was performed in 19 healthy nonsmoking volunteers at rest. Perfusion was assessed in the early phase of the study using a curve fit method over the first 90 sec. Nitrogen-13 accumulation (static PET) was assessed 4 to 8 min after injection. Each study was normalized to a mean of 100. The average distribution of normalized perfusion and activity was calculated in 24 segments. Heterogeneity of both activity and perfusion distribution were assessed and the activity distribution was compared with perfusion distribution. RESULTS: Perfusion distribution was homogeneous, with the exception of the inferior and apical regions. Activity distribution was inhomogeneous, with a lower activity in the posterolateral and apical regions. In the whole left ventricle, significant differences in distribution were found between static and dynamic imaging. CONCLUSION: Perfusion distribution was significantly different on dynamic images compared to static images. The posterolateral defect was not found on dynamic images. The posterolateral defect and other inhomogeneities in activity distribution are caused by tracer-dependent features, probably a redistribution of metabolites of 13N-ammonia.
Adult↗
The presence of progesterone receptors in arachnoid granulations and in the lining of arachnoid cysts: its relevance to expression of progesterone receptors in meningiomas.
Progesterone receptors (PR) were identified with an enzyme immunoassay in cytosols from human arachnoid granulations and arachnoid cysts. Meningiomas presumably originate from subdural endothelium which is abundantly present in these structures. In the three cases studied, oestrogen receptors were absent. The presence of PR in subdural endothelium may provide further ground for the expression of PR in meningiomas.
Adult↗
Quantitative myocardial mapping of perfusion and metabolism using parametric polar map displays in cardiac PET.
UNLABELLED: Most efficacy studies of cardiac PET in demonstrating myocardial ischemia and viability have been performed using one or more transversal static images of the heart. In contrast, in this paper we describe a method of functional imaging of the complete left ventricular myocardium for perfusion with nitrogen-13-ammonia, both at rest and during a dipyridamol stress test, and of glucose metabolism with 18F-fluorodeoxyglucose (18FDG). METHODS: This was performed by using the data of each of 48 radial segments of 10 short-axis images as tissue data and LV cavity data of three basal planes as blood pool data. The study describes the results of 19 normal volunteers and 36 patients with coronary artery disease. From the data of the normal volunteers a 95% normal confidence interval was calculated for each imaging modality. These intervals were then used to describe the patient data as normal, ischemic or infarcted. RESULTS: The results of analysis of the parametric images was compared with the results of static analysis of the same patient data and found to be less dependant on the detection threshold used. CONCLUSION: The described method enables the routine application of functional PET imaging of the total myocardium by the semi-automatic construction of parametric flow and metabolism polar maps. It thus provides an increased performance in the diagnosis, quantification and localization of myocardial ischemia and viability over conventional PET imaging.
Adult↗
Detection of lymph node metastases of squamous-cell cancer of the head and neck with FDG-PET and MRI.
UNLABELLED: The uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in neck lymph nodes of twelve patients with a squamous-cell carcinoma of the oral cavity was studied with PET in order to detect and locate lymphogenic metastases. METHODS: The results of FDG-PET imaging were compared with clinical, MRI and histopathologic findings. Standardized uptake values (SUV) were also calculated. RESULTS: A sensitivity of 91% and a specificity of 88% were calculated for FDG-PET. In contrast, a sensitivity of 36% and a specificity of 94% were calculated for MRI. Calculated SUVs for reactive lymph nodes, metastatic lymph nodes and the primary tumor were undifferentiated. CONCLUSION: Using FDG-PET, lymph node metastases of squamous-cell carcinomas of the oral cavity can be visualized with a high sensitivity and specificity. FDG-PET can be an improvement in the evaluation of the neck.
Aged↗
In vivo protein synthesis rate determination in primary or recurrent brain tumors using L-[1-11C]-tyrosine and PET.
UNLABELLED: The applicability of protein synthesis rate (PSR) determination with L-[1-11C]tyrosine (11C-TYR) and PET was assessed in patients suspected of a primary or recurrent brain tumor. METHODS: Simultaneous to intravenous injection of 265 MBq of 11C-TYR, dynamic PET acquisition was started and continued for 50 min. Arterial samples were taken and analyzed for 11C-TYR and metabolites. Based on this data, a model was proposed and the corresponding PSR calculated. RESULTS: Plasma metabolites were 11CO2, 11C-proteins and 11C-L-DOPA, constituting more than 50% of total plasma radioactivity at 40 min postinjection. Plasma 11CO2 reached a plateau of around 25% of total plasma radioactivity at 20 min postinjection. Plasma 11C-protein was not detected before 10 min postinjection, but increased exponentially afterwards to 20% at 40 min postinjection. Plasma 11C-L-DOPA was the only acid-soluble radioactive metabolite detected and was less than 8% at 40 min postinjection. Using a five-compartment model, it was shown that while the net PSR was dependent on the recycling of amino acids from protein, the amino acid incorporation was not, which was thus used for subsequent analysis. It was found that our curve-fitting results were unreliable due to the exchange of 11C-TYR between plasma and erythrocytes whereas the graphical Patlak-Gjedde analysis is hardly influenced by this transport phenomenon. The average amino acid incorporation rate thus calculated was 0.7 nmole/ml.min for nontumor tissue with a tumor versus nontumor average ratio of 1.7. CONCLUSION: The assessment of the PSR with TYR-PET is valuable and relatively simple to implement clinically.
Adult↗
Synthesis of 6 alpha-[18F]fluoroprogesterone: a first step towards a potential receptor-ligand for PET.
6 alpha-[18F]Fluoroprogesterone 3 was prepared by the BF3.Et2O-catalyzed reaction of progest-5 alpha, 6 alpha-epoxy-3,20-bisketal 1 and [18F]fluoride as a possible route for the in vivo visualization of progesterone receptors by PET. The radiochemical yield of 3 was 25% (EOB) and the sp. act. was 5 MBq/mumol (100 Ci/mol, EOS).
Deuterium Oxide↗
Contribution of magnetic resonance spectroscopic imaging and L-[1-11C]tyrosine positron emission tomography to localization of cerebral gliomas for biopsy.
Proton magnetic resonance spectroscopic imaging (1H-MRSI) and positron emission tomography with the tracer L-[1-11C]tyrosine (11C-TYR) were used to localize gliomas for biopsy or resection. This is especially helpful in cases of low-grade gliomas, if these lesions are not visualized by contrast-enhanced computed tomographic and magnetic resonance imaging scans. The clues to improved localization are provided by changes in tissue metabolite contents, such as elevation of phosphocholine, indicating cellular proliferation; decrease of N-acetylaspartate, denoting loss of neurons (as these are replaced by tumor cells); and elevation of lactate, pointing to the prevalence of glycolysis, as observed in many tumors. These data on tissue metabolite content have been obtained in vivo in the patient by proton magnetic resonance spectroscopy; metabolite maps derived from these data then visualize the distribution of the various metabolites over the section of the brain under investigation. Alternatively, localization of a tumor may be achieved by means of positron emission tomography depicting the pattern of uptake of the amino acid tracer 11C-TYR, as it tends to be incorporated in the process of cellular proliferation and protein biosynthesis. Five cases are presented as examples.
Adult↗
Synthesis and in vivo distribution in the rat of several fluorine-18 labeled N-fluoroalkylaporphines.
A method is described for the rapid production and purification of new potential dopamine agonists. Via microwave heating 10,11-dihydroxy-N-(n-2-fluoroethyl)norapomorphine (FNEA), 10,11-dihydroxy-N-(n-3-fluoropropyl)norapomorphine (FNPA) and 2,10,11-trihydroxy-N-(n-3-fluoropropyl)norapomorphine (FTNPA) and their isotopic fluorine-18 derivatives were synthesized. The fluorine-18 label was introduced via N-fluoroalkylation of acylated noraporphine derivatives with no-carrier-added (n.c.a.) 18FCH2CH2I and 18FCH2CH2CH2I. Within 160 min (E.O.B.), radiochemical yields of 13-29% (corrected for decay) were achieved based on [18F]fluoroalkyliodide. The specific activity obtained, ranged from 15 to 75 GBq/mumol. The fluorine-18 labeled compounds were investigated for their in vivo binding potency to the D2-receptors. After i.v. injection, the distribution was studied in rats. High uptakes of the N-[18F]fluoroalkylaporphines were found in the lungs, liver, adrenals and kidneys. No significant different radioactive accumulation was observed in striatum, cerebellum and frontal cortex. Dopamine depletion with reserpine did not affect the striatum to cerebellum ratio at low dosage of N-[18F]fluoroalkylaporphines (10 nmol/kg).
Animals↗
Synthesis and in vivo distribution in the rat of a dopamine agonist: N-([11C]methyl)norapomorphine.
A method for the rapid production and purification of 10,11-dihydroxy-N-([11C]methyl)norapomorphine ([11C]APO), a dopamine agonist (DA), is described. The potency of this ligand for studying the D2-receptors was examined. The label was introduced by N-methylation of norapomorphine hydrobromide with no-carrier-added (n.c.a) [11C]CH3I, produced from cyclotron-produced [11C]carbon dioxide. In 60 min (EOB) a radiochemical yield of 15% (corrected for decay) was achieved, based on [11C]CH3I. The specific activity ranged from 5 to 11 GBq/mumol. The distribution, after intravenous injection, was studied in rats. The radioactivity level in the striatum was higher than in the cerebellum and frontal cortex and was decreased after D2-blockade. The highest uptake ratio (1.47) was found at 30 min after injection. Dopamine depletion with reserpine did increase the striatum/cerebellum ratio at a low dosage of [11C]APO (10 nmol/kg). High uptakes of [11C]apomorphine were found in the lungs, liver and kidneys.
Animals↗
Uptake of radioligands by rat heart and lung in vivo: CGP 12177 does and CGP 26505 does not reflect binding to beta-adrenoceptors.
The biodistribution of (-)-4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H-benzimidazol-2-one (CGP12177, a non-selective beta-adrenoceptor antagonist) and 1-[2-(3-carbamoyl-4-hydroxy)-(5-3H-phenoxy)]-2-propanol methanesulfonate, (CGP26505, a beta 1-adrenoceptor antagonist) was studied in rats pretreated with various alpha- and beta-adrenoceptor blocking drugs (5 min before 3H injection, in dosages at which the drugs demonstrated the expected selectivity). Cardiac and pulmonary radioactivity were measured after 10 min, when specific binding was maximal. Uptake of [3H]CGP12177 was linked to binding to beta-adrenoceptors since it was not affected by prazosin or yohimbine, and was equally well inhibited by propranolol, unlabelled CGP12177 and isoprenaline. Moreover, atenolol and CGP20712A inhibited [3H]CGP12177 uptake in heart (predominantly beta 1-adrenoceptors) more potently than ICI 118,551, while in lungs (predominantly beta 2-adrenoceptors) ICI 118,551 was more potent than atenolol or CGP20712A. In contrast, [3H]CGP26505 uptake in the target organs was equally effectively inhibited by propranolol and ICI 118,551, and significantly lowered by alpha-adrenoceptor antagonists. We conclude that [11C]CGP12177, but not [11C]CGP2605 will be suitable for positron emission tomography imaging of beta-adrenoceptors in animals.
Adrenergic alpha-Antagonists↗
Amino acids for the measurement of protein synthesis in vivo by PET.
In principle, PET in combination with amino acids labelled with positron-emitting radionuclides and kinetic metabolic models, can quantify local protein synthesis rates in tissue in vivo. These PET measurements have clinical potential in, for example, oncology, neurology and psychiatry. An optimal positron-emitting amino acid for the measurement of PSR has a high protein incorporation, can easily be prepared by automated equipment and has minimal non-protein radioactive metabolites. Presently L-[methyl-11C]methionine, L-[1-11C]leucine, L-[1-11C]tyrosine, L-[1-11C]phenylalanine, L-[1-11C]methionine and L-[2-18F]fluorotyrosine are under evaluation in normal volunteers and/or in patients. Several other amino acids are suggested. No comparison of the clinical usefulness of the different amino acids in man is yet available. Because of the longer half life of 18F compared to 11C, [18F]fluoro amino acids may have advantages over [11C]amino acids for the investigation of tissue with relative slow protein synthesis, such as brain, and for application in institutions with an off site, but nearby cyclotron. The half life of [13N]amino acids is considered to be too short for flexible clinical application. As yet no metabolic compartmental model has been investigated for [13N]amino acids. For routine application reliable preparation of the radiopharmaceutical is essential. Of all the amino acids under evaluation, a reliable, high yield, easy to automate production procedure is available for L-[methyl-11C]methionine only. It is however unlikely that this tracer can accurately measure PSR because of its non-protein metabolism. For the other amino acids the main problems in production are associated with complex multistep syntheses and/or low radiochemical yields, complex purification methods and the need to isolate the L-enantiomer. The kinetic metabolic models under investigation, consist of 4 or 5 compartments depending on the necessity to compensate for labelled metabolites. The metabolic profile of the amino acids is mainly extracted from animal experiments. Because of the number and amount of labelled metabolites in plasma, [11C]carboxylic labelled amino acids are preferred to amino acids with carbon-11 in another position. As yet no recommendation can be given on the optimal labelled amino acid(s) for PSR measurement in vivo nor on the methods to prepare the amino acids reported for this purpose.
Amino Acids↗