18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism: initial UK experience from a technologist's perspective.

Science.gov (United States)

Meintjes, Marguerite; Endozo, Raymond; Dickson, John; Erlandsson, Kjel; Hussain, Khalid; Townsend, Caroline; Menezes, Leon; Bomanji, Jamshed

2013-06-01

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infants and children. Histologically, there are two subgroups, diffuse and focal. The aim of this study was to evaluate the accuracy of (18)F-fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET/computed tomography (CT) and contrast-enhanced CT in distinguishing between focal and diffuse lesions in infants with CHI who are unresponsive to medical therapy. In addition, this paper describes the detailed protocol used for imaging and analysis of (18)F-DOPA PET/CT images in our clinical practice. Twenty-two (18)F-DOPA PET/CT and contrast-enhanced CT imaging studies were carried out on 18 consecutive patients (nine boys and nine girls) with CHI (median age, 2 years and 1 month; range, 1-84 months) who had positive dominant ABCC8 mutation genetic results or negative ABCC8/t results but did not respond to first-line medical therapy with high-dose diazoxide. (18)F-DOPA was produced by the cyclotron unit of Woolfson Molecular Imaging Centre, Manchester, and transported to our centre in central London after synthesis and implementation of quality control measures. (18)F-DOPA was administered intravenously at a dose of 4 MBq/kg, and iodine contrast medium was injected intravenously at a dose of 1.5 ml/kg. Single bed position PET/CT images of the pancreas were acquired under light sedation with oral chloral hydrate. Four PET dynamic data acquisition scans were taken 20, 40, 50 and 60 min after injection for a duration of 10 min each. The results were assessed by visual interpretation and quantitative measurements of standardized uptake values (SUVs) in the head, body, and tail of the pancreas. Of the 18 patients, 13 showed diffuse and five showed focal (18)F-DOPA PET pancreatic uptake. Three regions of interest were drawn over the head, body and tail of the pancreas to calculate the SUV(max). Using the formula - highest SUV(max)/next highest SUV(max) - a ratio was calculated. Five patients had

Clinical value of {sup 18}F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ({sup 18}F-DOPA PET/CT) for detecting pheochromocytoma

Energy Technology Data Exchange (ETDEWEB)

Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Karges, Wolfram [RWTH Aachen, Division of Endocrinology and Diabetes, Aachen (Germany); Pauls, Sandra [University of Ulm, Department of Radiology, Ulm (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Dralle, Henning [University Halle-Wittenberg, Department of General, Visceral and Vascular Surgery, Halle (Germany); Neumaier, Bernd [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Max-Planck-Institut fuer Neurologische Forschung, Section for Radiochemistry, Cologne (Germany); Mottaghy, Felix M. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany)

2010-03-15

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor {sup 18}F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined {sup 18}F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. {sup 18}F-DOPA PET, CT and {sup 18}F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of {sup 18}F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. {sup 18}F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do {sup 18}F-DOPA PET or CT alone. (orig.)

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma

International Nuclear Information System (INIS)

Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna; Frech, Andreas; Fraedrich, Gustav; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias

2013-01-01

18 F-Fluoro-l-dihydroxyphenylalanine ( 18 F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by 68 Ga-DOTA-Tyr 3 -octreotide ( 68 Ga-DOTA-TOC) PET. Therefore, we compared 68 Ga-DOTA-TOC and 18 F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with 68 Ga-DOTA-TOC PET and 18 F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV max ) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, 68 Ga-DOTA-TOC PET and 18 F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of 68 Ga-DOTA-TOC was 100 % and that of 18 F-DOPA PET was 56.0 %. Overall, 68 Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and 18 F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of 68 Ga-DOTA-TOC PET was 100 % (McNemar, P 18 F-DOPA PET was 71.1 % (McNemar, P max (mean ± SD) of all 32 concordant lesions was 67.9 ± 61.5 for 68 Ga-DOTA-TOC PET and 11.8 ± 7.9 for 18 F-DOPA PET (Mann-Whitney U test, P 68 Ga-DOTA-TOC PET may be superior to 18 F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma.

Science.gov (United States)

Kroiss, Alexander; Putzer, Daniel; Frech, Andreas; Decristoforo, Clemens; Uprimny, Christian; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias; Fraedrich, Gustav; Virgolini, Irene Johanna

2013-12-01

(18)F-Fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTA-TOC) PET. Therefore, we compared (68)Ga-DOTA-TOC and (18)F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with (68)Ga-DOTA-TOC PET and (18)F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, (68)Ga-DOTA-TOC PET and (18)F-DOPA PET each had a per-patient and per-lesion detection rate of 100% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of (68)Ga-DOTA-TOC was 100% and that of (18)F-DOPA PET was 56.0%. Overall, (68)Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and (18)F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of (68)Ga-DOTA-TOC PET was 100% (McNemar, P TOC PET and 11.8 ± 7.9 for (18)F-DOPA PET (Mann-Whitney U test, P TOC PET may be superior to (18)F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically inoperable tumours and metastatic or multifocal disease.

Blood-brain transfer and metabolism of 6-[18F]fluoro-L-dopa in rat

International Nuclear Information System (INIS)

Reith, J.; Dyve, S.; Kuwabara, H.; Guttman, M.; Diksic, M.; Gjedde, A.

1990-01-01

In a study designed to reveal the rates of blood-brain transfer and decarboxylation of fluoro-L-3,4-dihydroxyphenylalanine (FDOPA), we discovered a major discrepancy between the DOPA decarboxylase activity reported in the literature and the rate of FDOPA decarboxylation measured in the study. Donor rats received intravenous injections of 6 mCi fluorine-18-labeled FDOPA. The donor rats synthesized methyl-FDOPA. Arterial plasma, containing both FDOPA and methyl-FDOPA, was sampled from the donor rats at different times and reinjected into recipient rats in which it circulated for 20 s. The blood-brain clearance of the mixture of labeled tracers in the plasma was determined by an integral method. The individual permeabilities were determined by linear regression analysis, according to which the average methyl-FDOPA permeability in the blood-brain barrier was twice that of FDOPA, which averaged 0.037 ml g-1 min-1. The permeability ratio was used to determine the fractional clearance from the brain of FDOPA (and hence of methyl-FDOPA), which averaged 0.081 min-1. In the striatum, the measured average FDOPA decarboxylation rate constant (kD3) was 0.010 min-1, or no more than 1% of the rate of striatal decarboxylation of DOPA measured in vitro and in vivo. We interpreted this finding as further evidence in favor of the hypothesis that striatum has two dopamine (DA) pools, of which only DA in the large pool is protected from metabolism. Hence, no more than 1% of the quantity of fluoro-DA theoretically synthesized was actually retained in striatum

[F-18]fluoro-meta-L-tyrosine is a better PET tracer than [F-18]fluoro-L-dopa for the delineation of dopaminergic structures in the human brain

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

1990-01-01

Fluorine-18 labelled fluoro-m-L-tyrosine (FmLtyr) and fluoro-L-Dopa (F-Dopa) have been synthesized, and the utility of FmLtyr for PET investigations of dopaminergic brain regions has been compared to that of F-dopa. Experimental results from both monkey and human studies indicate that FmLtyr gives better delineation of striatum, and is a better PET tracer than F-dopa

Grading and outcome prediction of pediatric diffuse astrocytic tumors with diffusion and arterial spin labeling perfusion MRI in comparison with 18F-DOPA PET

Energy Technology Data Exchange (ETDEWEB)

Morana, Giovanni; Tortora, Domenico; Severino, Mariasavina; Rossi, Andrea [Istituto Giannina Gaslini, Neuroradiology Unit, Genoa (Italy); Piccardo, Arnoldo; Cabria, Manlio [Ente Ospedaliero Ospedali Galliera, Nuclear Medicine Unit, Genoa (Italy); Puntoni, Matteo [Ente Ospedaliero Ospedali Galliera, Clinical Trial Unit, Scientific Directorate, Genoa (Italy); Nozza, Paolo [Istituto Giannina Gaslini, Pathology Unit, Genoa (Italy); Ravegnani, Marcello; Consales, Alessandro; Mascelli, Samantha; Raso, Alessandro [Istituto Giannina Gaslini, Neurosurgery Unit, Genoa (Italy); Verrico, Antonio; Milanaccio, Claudia [Istituto Giannina Gaslini, Neuro-oncology Unit, Genoa (Italy)

2017-11-15

The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI) and arterial spin labeling (ASL) perfusion imaging in comparison with {sup 18}F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic performance in tumor grading and outcome prediction in pediatric patients with diffuse astrocytic tumors (DAT). We retrospectively analyzed 26 children with histologically proven treatment naive low and high grade DAT who underwent ASL and DWI performed within 2 weeks of {sup 18}F-DOPA PET. Relative ASL-derived cerebral blood flow max (rCBF max) and DWI-derived minimum apparent diffusion coefficient (rADC min) were compared with {sup 18}F-DOPA uptake tumor/normal tissue (T/N) and tumor/striatum (T/S) ratios, and correlated with World Health Organization (WHO) tumor grade and progression-free survival (PFS). Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation, receiver operating characteristic (ROC) analysis, discriminant function analysis (DFA), Kaplan-Meier survival curve, and Cox analysis. A significant correlation was demonstrated between rCBF max, rADC min, and {sup 18}F-DOPA PET data (p < 0.001). Significant differences in terms of rCBF max, rADC min, and {sup 18}F-DOPA uptake were found between low- and high-grade DAT (p ≤ 0.001). ROC analysis and DFA demonstrated that T/S and T/N values were the best parameters for predicting tumor progression (AUC 0.93, p < 0.001). On univariate analysis, all diagnostic tools correlated with PFS (p ≤ 0.001); however, on multivariate analysis, only {sup 18}F-DOPA uptake remained significantly associated with outcome (p ≤ 0.03), while a trend emerged for rCBF max (p = 0.09) and rADC min (p = 0.08). The combination of MRI and PET data increased the predictive power for prognosticating tumor progression (AUC 0.97, p < 0.001). DWI, ASL and {sup 18}F-DOPA PET provide useful complementary information for pediatric DAT grading. {sup 18}F-DOPA uptake

Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery

Energy Technology Data Exchange (ETDEWEB)

Cicone, Francesco; Papa, Annalisa; Scopinaro, Francesco [Sant' Andrea Hospital, Rome (Italy). Unit of Nuclear Medicine; ' ' Sapienza' ' Univ., Rome (Italy). Dept. of Surgical and Medicine Sciences and Translational Medicine; Minniti, Giuseppe; Scaringi, Claudia; Maurizi Enrici, Riccardo [' ' Sapienza' ' Univ., Rome (Italy). Dept. of Surgical and Medicine Sciences and Translational Medicine; Sant' Andrea Hospital, Rome (Italy). Unit of Radiotherapy; Romano, Andrea; Tavanti, Francesca; Bozzao, Alessandro [Sant' Andrea Hospital, Rome (Italy). Unit of Neuroradiology; Rome Univ. (Italy). Dept. of Neurosciences, Mental Health and Sensory Organs (Ne.S.M.O.S.)

2015-01-15

We assessed the performance of 6-[{sup 18}F]-fluoro-l-3,4-dihydroxyphenylalanine (F-DOPA) PET for differentiating radionecrosis (RN) from tumour progression (PD) in a population of patients with brain metastases, treated with stereotactic radiosurgery. The accuracy of F-DOPA PET was compared with that of perfusion-weighted magnetic resonance (perfusion-MR). In 42 patients with a total of 50 brain metastases from various primaries F-DOPA PET/CT was performed because of suspected radiological progression at the site of previously irradiated brain metastasis. Several semiquantitative PET parameters were recorded, and their diagnostic accuracy was compared by receiver operating characteristic curve analyses. The diagnosis was established by either surgery or follow-up. A comparison was made between F-DOPA PET and perfusion-MR sequences acquired no more than 3 weeks apart. Definitive outcome was available in 46 of the 50 lesions (20 PD, 26 RN). Of the 46 lesions, 11 were surgically excised while in the remaining 35 lesions the diagnosis was established by radiological and clinical criteria. The best diagnostic performance was obtained using the semiquantitative PET parameter maximum lesion to maximum background uptake ratio (SUVL{sub max}/Bkgr{sub max}). With a cut-off value of 1.59, a sensitivity of 90 % and a specificity of 92.3 % were achieved in differentiating RN from PD lesions (accuracy 91.3 %). Relative cerebral blood volume (rCBV) derived from perfusion-MR was available for comparison in 37 of the 46 metastases. Overall accuracy of rCBV was lower than that of all semiquantitative PET parameters under study. The best differentiating rCBV cut-off value was 2.14; this yielded a sensitivity of 86.7 % and a specificity of 68.2 % (accuracy 75.6 %). F-DOPA PET is a highly accurate tool for differentiating RN from PD brain metastases after stereotactic radiosurgery. In this specific setting, F-DOPA PET seems to perform better than perfusion-MR. (orig.)

A retrospective comparison between {sup 68}Ga-DOTA-TOC PET/CT and {sup 18}F-DOPA PET/CT in patients with extra-adrenal paraganglioma

Energy Technology Data Exchange (ETDEWEB)

Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Frech, Andreas; Fraedrich, Gustav [Innsbruck Medical University, Department of Vascular Surgery, Innsbruck (Austria); Gasser, Rudolf Wolfgang [Innsbruck Medical University, Department of Internal Medicine I, Innsbruck (Austria); Shulkin, Barry Lynn [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Url, Christoph [Innsbruck Medical University, Department of Otorhinolaryngology, Innsbruck (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Prommegger, Rupert [Sanatorium Kettenbruecke, Department of Surgery, Innsbruck (Austria); Sprinzl, Georg Mathias [State Clinic St. Poelten, Department of Otorhinolaryngology, St. Poelten (Austria)

2013-12-15

{sup 18}F-Fluoro-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by {sup 68}Ga-DOTA-Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) PET. Therefore, we compared {sup 68}Ga-DOTA-TOC and {sup 18}F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV{sub max}) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of {sup 68}Ga-DOTA-TOC was 100 % and that of {sup 18}F-DOPA PET was 56.0 %. Overall, {sup 68}Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and {sup 18}F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of {sup 68}Ga-DOTA-TOC PET was 100 % (McNemar, P < 0.5), and that of {sup 18}F-DOPA PET was 71.1 % (McNemar, P < 0.001). The SUV{sub max} (mean {+-} SD) of all 32 concordant lesions was 67.9 {+-} 61.5 for {sup 68}Ga-DOTA-TOC PET and 11.8 {+-} 7.9 for {sup 18}F-DOPA PET (Mann-Whitney U test, P < 0.0001). {sup 68}Ga-DOTA-TOC PET

The applications of 18F-DOPA PET in Parkinson's disease

International Nuclear Information System (INIS)

Zuo Chuantao

2000-01-01

The injury of the presynaptic nigro-striae dopaminergic projection is the important mechanism of Parkinson's disease (PD). 18 F-DOPA PET provides a measure of the structure as well as the biochemical integrity of the dopaminergic neurons, which contribute to the early diagnosis, differentiation diagnosis, prognosis evaluation of PD

Comparative assessment of 6-[18 F]fluoro-L-m-tyrosine and 6-[18 F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson's disease rat model.

Science.gov (United States)

Becker, Guillaume; Bahri, Mohamed Ali; Michel, Anne; Hustadt, Fabian; Garraux, Gaëtan; Luxen, André; Lemaire, Christian; Plenevaux, Alain

2017-05-01

Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson's disease (PD), in vivo quantitative imaging of dopamine (DA) containing neurons in animal models of PD is of critical importance in the preclinical evaluation of highly awaited disease-modifying therapies. Among existing methods, the high sensitivity of positron emission tomography (PET) is attractive to achieve that goal. The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6-OHDA) lesioned rats using two dopaminergic PET radiotracers, namely [ 18 F]fluoro-3,4-dihydroxyphenyl-L-alanine ([ 18 F]FDOPA) and 6-[ 18 F]fluoro-L-m-tyrosine ([ 18 F]FMT). Because the imaging signal is theoretically less contaminated by metabolites, we hypothesized that the latter would show stronger relationship with behavioural and post-mortem measures of striatal dopaminergic deficiency. We used a within-subject design to measure striatal [ 18 F]FMT and [ 18 F]FDOPA uptake in eight partially lesioned, eight fully lesioned and ten sham-treated rats. Animals were pretreated with an L-aromatic amino acid decarboxylase inhibitor. A catechol-O-methyl transferase inhibitor was also given before [ 18 F]FDOPA PET. Quantitative estimates of striatal uptake were computed using conventional graphical Patlak method. Striatal dopaminergic deficiencies were measured with apomorphine-induced rotations and post-mortem striatal DA content. We observed a strong relationship between [ 18 F]FMT and [ 18 F]FDOPA estimates of decreased uptake in the denervated striatum using the tissue-derived uptake rate constant K c . However, only [ 18 F]FMT K c succeeded to discriminate between the partial and the full 6-OHDA lesion and correlated well with the post-mortem striatal DA content. This study indicates that the [ 18 F]FMT could be more sensitive, with respect of [ 18 F]FDOPA, to investigate DA terminals loss in 6-OHDA rats, and open the way to in vivo L

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism. A blinded evaluation

International Nuclear Information System (INIS)

Dahl Christiansen, Charlotte; Helleskov Rasmussen, Annett; Petersen, Henrik; Lerberg Nielsen, Anne; Detlefsen, Soenke; Brusgaard, Klaus; Rasmussen, Lars; Hovendal, Claus; Melikyan, Maria; Ekstroem, Klas; Globa, Evgenia; Christesen, Henrik Thybo

2018-01-01

Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3 -octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged. (orig.)

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism. A blinded evaluation

Energy Technology Data Exchange (ETDEWEB)

Dahl Christiansen, Charlotte; Helleskov Rasmussen, Annett [Hans Christian Andersen Children' s Hospital, Odense University Hospital, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Petersen, Henrik; Lerberg Nielsen, Anne [Odense University Hospital, Department of Nuclear Medicine, Odense (Denmark); Detlefsen, Soenke [University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Department of Pathology, Odense (Denmark); Brusgaard, Klaus [Odense University Hospital, Department of Clinical Genetics, Odense (Denmark); Rasmussen, Lars; Hovendal, Claus [Odense University Hospital, Department of Abdominal Surgery, Odense (Denmark); Melikyan, Maria [Endocrine Research Centre, Moscow (Russian Federation); Ekstroem, Klas [Karolinska Hospital, Astrid Lindgren Children' s Hospital, Stockholm (Sweden); Globa, Evgenia [MOH of Ukraine, Ukrainian Center of Endocrine Surgery, Endocrine Organs and Tissue Transplantation, Kyiv (Ukraine); Christesen, Henrik Thybo [Hans Christian Andersen Children' s Hospital, Odense University Hospital, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Odense Pancreas Center (OPAC), Odense (Denmark); Odense University Hospital, Department of Paediatrics, Odense C (Denmark)

2018-02-15

Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3 -octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV{sub max}) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV{sub max} ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV{sub max} cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged. (orig.)

18F-DOPA PET/CT Physiological Distribution and Pitfalls: Experience in 215 Patients.

Science.gov (United States)

Calabria, Ferdinando F; Chiaravalloti, Agostino; Jaffrain-Rea, Marielise L; Zinzi, Maddalena; Sannino, Pasqualina; Minniti, Giuseppe; Rubello, Domenico; Schillaci, Orazio

2016-10-01

F-DOPA PET/CT is potentially helpful in the management of patients with low-grade brain tumors, movement disorders, and somatic neuroendocrine tumors. We describe the whole-body physiological distribution of F-DOPA uptake. We examined 215 patients with F-DOPA PET/CT. Among these, 161 had brain scans and 54 had whole-body scans. Physiological distribution was negligible in the brain, with the exception of basal ganglia, whereas greatest activity was noted in the liver, pancreas, other exocrine glands, and the urinary system. Incidental tracer uptake sites were identified in 5.5% of patients. Some of these findings were due to inflammation, whereas in most cases, uptake was seen in benign tumors of the brain or in the endocrine or exocrine glands. F-DOPA uptake may be seen in inflammatory tissue or benign tumors. Correlations with history, physical examination, laboratory examination, CT, MRI, and histology are necessary for optimal diagnosis.

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation.

Science.gov (United States)

Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg; Detlefsen, Sönke; Brusgaard, Klaus; Rasmussen, Lars; Melikyan, Maria; Ekström, Klas; Globa, Evgenia; Rasmussen, Annett Helleskov; Hovendal, Claus; Christesen, Henrik Thybo

2018-02-01

Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.

Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

International Nuclear Information System (INIS)

Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

2008-01-01

18 F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18 F-DOPA and 68 Ga-DOTA-NOC are more accurate for disease assessment and 68 Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare 68 Ga-DOTA-NOC and 18 F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18 F-DOPA and 68 Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68 Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18 F-DOPA PET was positive in 9/13. On a lesions basis, 68 Ga-DOTA-NOC identified more lesions than 18 F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68 Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18 F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that 68 Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18 F-DOPA. (orig.)

Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours.

Science.gov (United States)

Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

2008-08-01

(18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.

Synthesis and evaluation of radioiodinated 6-Iodo-L-DOPA as a cerebral L-amino acid transport marker

International Nuclear Information System (INIS)

Kawai, K.; Ohta, H.; Kubodera, A.; Channing, M.A.; Eckelman, W.C.

1996-01-01

Regioselective radioiodination of N-trifluoroacetyl 3,4-dimethoxy-6-trifluoroacetoxymercurio-L-phenylalanine ethyl ester 1 under no-carrier-added condition gave 6-[ 125 I]iodo protected L-DOPA with a labeling efficiency of more than 85%, and no-carrier-added 6-[ 125 I]I-L-DOPA was obtained with a radiochemical purity of over 95% after hydrolysis and chromatography. A nonradioactive standard of 6-iodo protected L-DOPA was synthesized by the iododemercuration of 6-mercuric trifluoroacetate protected L-DOPA 1 using I 2 in chloroform. 6-[ 125 I]I-L-DOPA showed high brain accumulation and rapid blood clearance in mice. The rat brain slice studies indicated high affinity of 6-[ 125 I]I-L-DOPA for carrier-mediated and stereoselective active transport systems. The tissue homogenate analysis revealed that most of the accumulated radioactivity was intact 6-[ 125 I]I-L-DOPA. Thus, 6-[ 123 I]I-L-DOPA appears to be a suitable single photon emission computed tomography (SPECT) tracer for the selective measurement of cerebral L-amino acid transport, having no affinity for dopamine metabolism

Enantioselective synthesis of 6-[18F] fluoro-L-DOPA

International Nuclear Information System (INIS)

Zhang Lan; Tang Ganghua; Zhou Wei; Li Junling; Yin Duanzhi; Wang Yongxian; Tang Xiaolan; Huang Zuhan

2002-01-01

Trimethylammonium veratraldehyde triflate was synthesized and used as a precurser for the synthesis of 6-[ 18 F] Fluoro-L-DOPA by using the chiral phase-transfer catalyst, O-Allyl-N-(9)-anthracenylcinchonidinium bromide which was also synthesized in this study. Based on these, 6-[ 18 F] Fluoro-L-DOPA was prepared with acceptable radiochemical yield (10 ± 3)% in short synthesis time (80 min), with high radiochemical purity, specific activity and chemical purity

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism

DEFF Research Database (Denmark)

Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg

2018-01-01

(68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. Methods: PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUVmax) by two independent examiners......, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Results: Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed...... in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut...

Improved GMP-compliant multi-dose production and quality control of 6-[18F]fluoro-L-DOPA.

Science.gov (United States)

Luurtsema, G; Boersma, H H; Schepers, M; de Vries, A M T; Maas, B; Zijlma, R; de Vries, E F J; Elsinga, P H

2017-01-01

6-[ 18 F]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) is a frequently used radiopharmaceutical for detecting neuroendocrine and brain tumors and for the differential diagnosis of Parkinson's disease. To meet the demand for FDOPA, a high-yield GMP-compliant production method is required. Therefore, this study aimed to improve the FDOPA production and quality control procedures to enable distribution of the radiopharmaceutical over distances.FDOPA was prepared by electrophilic fluorination of the trimethylstannyl precursor with [ 18 F]F 2 , produced from [ 18 O] 2 via the double-shoot approach, leading to FDOPA with higher specific activity as compared to FDOPA which was synthesized, using [ 18 F]F 2 produced from 20 Ne, leading to FDOPA with a lower specific activity. The quality control of the product was performed using a validated UPLC system and compared with quality control with a conventional HPLC system. Impurities were identified using UPLC-MS. The [ 18 O] 2 double-shoot radionuclide production method yielded significantly more [ 18 F]F 2 with less carrier F 2 than the conventional method starting from 20 Ne. After adjustment of radiolabeling parameters substantially higher amounts of FDOPA with higher specific activity could be obtained. Quality control by UPLC was much faster and detected more side-products than HPLC. UPLC-MS showed that the most important side-product was FDOPA-quinone, rather than 6-hydroxydopa as suggested by the European Pharmacopoeia. The production and quality control of FDOPA were significantly improved by introducing the [ 18 O] 2 double-shoot radionuclide production method, and product analysis by UPLC, respectively. As a result, FDOPA is now routinely available for clinical practice and for distribution over distances.

P04.02 Analysis of 18F-DOPA PET imaging for target volume definition in patients with recurrent glioblastoma treated with proton therapy

Science.gov (United States)

Amelio, D.; Scartoni, D.; Palucci, A.; Vennarini, S.; Giacomelli, I.; Lemoine, S.; Donner, D.; Farace, P.; Chierichetti, F.; Amichetti, M.

2017-01-01

.006). The overlapping volume (mean 5.7 ± 3.3 cc) was quite small compared to each single volume and suggest that relevant part of MRIGTV is not covered by BTV as well as that relevant part of BTV is not covered by MRGTV. In line with such results we recorded also a low CI (mean 0.26 ± 0.2). The PT irradiation of PET-integrated target volumes provided a median progression-free survival (PFS) of 6 months, while the 6-month PFS rate was 57%; median survival after PT was 8.7 months, while 9-month survival rate was 60%. Conclusions: Target volume definition for rGBM undergoing PT re-irradiation may yield significantly differing results depending upon the imaging modality used for target contouring. Our data suggest that 18F-DOPA PET can detect relevant non-enhancing pathological areas outside the conventional MRGTV ultimately yielding to larger volumes to be irradiated. Influence on clinical outcomes deserves further evaluation.

Comparison of (68)Ga-DOTA-Tyr(3)-octreotide and (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography in neuroendocrine tumor patients.

Science.gov (United States)

Putzer, D; Gabriel, M; Kendler, D; Henninger, B; Knoflach, M; Kroiss, A; Vonguggenberg, E; Warwitz, B; Virgolini, I J

2010-02-01

(68)Ga-DOTA-Tyr3-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) and (18)F-fluoro-L-dihydroxyphenylalanine PET ((18)F-DOPA PET) are emerging modalities for imaging of neuroendocrine tumors. This study reports our initial experiences with these two PET modalities on initial diagnosis, staging and restaging in NET patients. Fifteen patients with NET underwent both (68)Ga-DOTA-TOC and (18)F-DOPA PET as well as computed tomography (CT). Image findings were compared on a patient-basis (pathological uptake: yes/no) as well as on a lesion-basis. Contrast-enhanced CT and histological follow-up served as gold standard. Furthermore, imaging results were matched with tumor marker levels and quantitative tracer uptake by the tumor lesions. When comparing (68)Ga-DOTA-TOC and (18)F-DOPA PET, each modality showed a sensitivity of 64% and a specificity of 100% on a patient-based analysis. (68)Ga-DOTA-TOC PET and (18)F-DOPA PET showed equal findings in 7 out of 15 patients and disagreement in 8 patients. (68)Ga-DOTA-TOC revealed more metastases than (18)F-DOPA PET in 6 patients, while (18)F-DOPA PET detected more metastases than (68)Ga-DOTA-TOC in 4 patients. By (68)Ga-DOTA-TOC PET, 208 malignant lesions were detected, while by (18)F-DOPA only 86 lesions were found, and in CT 124, respectively. (68)Ga-DOTA-TOC and (18)F-DOPA PET are useful tools in the detection and staging of NET lesions. Our initial results allow the conclusion that (68)Ga-DOTA-TOC PET may have a stronger clinical impact in NET patients, as it does not only offer diagnostic information, but is decisive for the further treatment management, i. e. PRRT, as well.

18F-DOPA PET/CT and MRI Findings in a Patient With Multiple Meningiomas.

Science.gov (United States)

Calabria, Ferdinando F; Chiaravalloti, Agostino; Calabria, Eros N; Grillea, Giovanni; Schillaci, Orazio

2016-08-01

A 56-year-old man was referred to our Department for a 2-year story of upper limb tremor, severe headache, and episodes of confusion. Brain F-DOPA PET/CT showed multiple areas of tracer uptake in the two hemispheres of the brain. Subsequent MRI displayed demyelinating foci with high contrast enhancement. Histological specimen confirmed the diagnosis of multiple meningiomas.

Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

International Nuclear Information System (INIS)

Rougemont, D.; Baron, J.C.; Collard, P.; Bustany, P.; Comar, D.; Agid, Y.

1983-06-01

Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and 18 F-Fluoro-2-deoxy-D-glucose ( 18 FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain

Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson's disease and healthy controls

International Nuclear Information System (INIS)

Eshuis, S.A.; Maguire, R.P.; Leenders, K.L.; Jager, P.L.; Jonkman, S.; Dierckx, R.A.

2009-01-01

Diagnosing Parkinson's disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity. (orig.)

18F-FDOPA Accumulation in Traumatic Rib Fractures : A Potential Pitfall

NARCIS (Netherlands)

Stormezand, Gilles N.; Glaudemans, Andor W. J. M.; Slart, Riemer H. J. A.

F-FDOPA (6-[F]fluoro-L-DOPA) is used for the detection and staging of neuroendocrine tumors by visualizing the uptake of amine precursors in these tumors with high sensitivity and specificity. However, as this tracer is only available in a limited number of centers worldwide and the minority of the

Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Rougemont, D; Baron, J C; Collard, P; Bustany, P; Comar, D; Agid, Y

1983-06-01

Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and /sup 18/F-Fluoro-2-deoxy-D-glucose (/sup 18/FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain.

Nature or Nurture? Determining the Heritability of Human Striatal Dopamine Function: an [18F]-DOPA PET Study

Science.gov (United States)

Stokes, Paul R A; Shotbolt, Paul; Mehta, Mitul A; Turkheimer, Eric; Benecke, Aaf; Copeland, Caroline; Turkheimer, Federico E; Lingford-Hughes, Anne R; Howes, Oliver D

2013-01-01

Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins. Nine MZ and 10 DZ twin pairs underwent high-resolution [18F]-DOPA PET to assess presynaptic striatal dopamine function. Uptake values for the overall striatum and functional striatal subdivisions were determined by a Patlak analysis using a cerebellar reference region. Heritability, shared environmental effects and non-shared individual-specific effects were estimated using a region of interest (ROI) analysis and a confirmatory parametric analysis. Overall striatal heritability estimates from the ROI and parametric analyses were 0.44 and 0.33, respectively. We found a distinction between striatal heritability in the functional subdivisions, with the greatest heritability estimates occurring in the sensorimotor striatum and the greatest effect of individual-specific environmental factors in the limbic striatum. Our results indicate that variation in overall presynaptic striatal dopamine function is determined by a combination of genetic factors and individual-specific environmental factors, with familial environmental effects having no effect. These findings underline the importance of individual-specific environmental factors for striatal dopaminergic function, particularly in the limbic striatum, with implications for understanding neuropsychiatric disorders such as schizophrenia and addictions. PMID:23093224

GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP 'Fluorodopa F 18 Injection'

International Nuclear Information System (INIS)

Kao, C.K.; Hsu Wenlin; Xie Hengli; Lin Mingchi; Lan Wenchun; Chao Haoyu

2011-01-01

Lately, 6-[ 18 F]fluoro-L-DOPA (FDOPA) has found increase in its clinical demand for whole-body positron emission tomography (PET) scans, and two key issues in fulfilling this demand are the difficulties in producing FDOPA under the recently imposed PET drug good manufacturing practice (GMP) regulations and in providing it in the quality meeting the terms of major compendia. This paper describes the approaches for the GMP production of FDOPA and for the product testing to meet the standard of United States Pharmacopeia (USP) 'Fluorodopa F 18 Injection.' FDOPA was produced by the carrier-added electrophilic aromatic substitution reaction in the facility complying Pharmaceutical Inspection Cooperation Scheme clean room standard. The special aseptic handling technique was applied to minimize the bioburden. The product quality control followed all testing items and procedures, including three different settings of high performance liquid chromatography (HPLC). The process yielded FDOPA average 2.60±0.26 GBq (N=22) in every batch. All qualities of the product were within the specifications described in the USP 'Fluorodopa F 18 Injection.' The entire production was audited by the government authority and certified to comply with the latest PET drug GMP regulation. Our efforts in producing FDOPA following all aspects of GMP requirements have resulted in a product with the USP quality and certified as GMP complied. The routine production yields enough doses for three to four whole-body scans in each batch. The issues discussed in the report provide good reference for producers planning in routine production for PET drugs that are not commonly produced or with complicated compendial quality control tests. (author)

Quantitative {sup 18}F-DOPA PET/CT in pheochromocytoma. The relationship between tumor secretion and its biochemical phenotype

Energy Technology Data Exchange (ETDEWEB)

Amodru, Vincent; Brue, Thierry; Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Conception University Hospital, Marseille (France); Guerin, Carole; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception University Hospital, Marseille (France); Delcourt, Sarkis; Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, European Center for Research in Medical Imaging, Marseille (France); Romanet, Pauline [Aix-Marseille University, Laboratory of Molecular Biology, Conception Hospital and CNRS, CRN2M UMR 7286, Marseille (France); Loundou, Anderson [Aix-Marseille University, Department of Public Health, EA3279 Self-perceived Health Assessment Research Unit, La Timone University, Marseille (France); Viana, Bruna; Pacak, Karel [National Institutes of Health, Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD (United States)

2018-02-15

{sup 18}F-FDOPA illustrates the properties of uptake and storage of catecholamines in pheochromocytomas (PHEOs). Until now, the relationship between {sup 18}F-FDOPA quantitative parameters and a PHEO secretory profile has not been specifically evaluated. Fifty-six patients (56% females, median age: 47.5 yrs) with non-metastatic PHEO, evaluated by {sup 18}F-FDOPA PET/CT, were included in this retrospective study. Forty-five patients had negative genetic testing (80.4%); five patients (8.9%) had RET, two patients (3.6%) had SDHB, two had SDHD (3.6%), one patient (1.8%) had NF1, and one patient had a VHL (1.8%) mutation. Correlation between {sup 18}F-FDOPA metabolic parameters (tumor SUVmax, tumor SUVmean, tumor SUVmax/liver SUVmax, MTV 42%, total lesion uptake), urinary metanephrines (MNs), and plasma chromogranin A (CgA) were evaluated. All patients had positive {sup 18}F-FDOPA PET/CT. On univariate analysis, there was a strong correlation between all metabolic parameters and urinary MNs and plasma chromogranin A (CgA). The highest correlations were observed between total lesion (TL) uptake and the value of urinary MNs regardless of their nature (p = 8.10{sup -15} and r = 0.80) and between MTV 42% and plasma CgA levels (p = 2.10{sup -9}, r = 0.74). On multivariate analysis, the correlation of uptake parameters and CgA levels did not persist further due to the relation of CgA and tumor diameter. A correlation between TL uptake and the normetanephrine/metanephrine ratio (NMN/MN) was also found, a finding that was in accordance with in vitro studies, which were found to have a higher catecholamine content in epinephrine producing PHEOs. This retrospective study shows a correlation between {sup 18}F-FDOPA uptake, especially using TL uptake, urinary MNs, and a PHEO biochemical phenotype. This illustrates that beyond its localization value, {sup 18}F-FDOPA PET further enables PHEO characterization at a specific metabolic level. (orig.)

Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma.

NARCIS (Netherlands)

Timmers, H.J.L.M.; Chen, C.C.; Carrasquillo, J.A.; Whatley, M.; Ling, A.; Havekes, B.; Eisenhofer, G.; Martiniova, L.; Adams, K.T.; Pacak, K.

2009-01-01

CONTEXT: Besides (123)I-metaiodobenzylguanidine (MIBG), positron emission tomography (PET) agents are available for the localization of paraganglioma (PGL), including (18)F-3,4-dihydroxyphenylalanine (DOPA), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), and (18)F-fluorodopamine ((18)F-FDA). OBJECTIVE:

Increasing feasibility and utility of 18F-FDOPA PET for the management of glioma

International Nuclear Information System (INIS)

Bell, Christopher; Dowson, Nicholas; Puttick, Simon; Gal, Yaniv; Thomas, Paul; Fay, Mike; Smith, Jye; Rose, Stephen

2015-01-01

Introduction: Despite radical treatment therapies, glioma continues to carry with it a uniformly poor prognosis. Patients diagnosed with WHO Grade IV glioma (glioblastomas; GBM) generally succumb within two years, even those with WHO Grade III anaplastic gliomas and WHO Grade II gliomas carry prognoses of 2–5 and 2 years, respectively. PET imaging with 18 F-FDOPA allows in vivo assessment of the metabolism of glioma relative to surrounding tissues. The high sensitivity of 18 F-DOPA imaging grants utility for a number of clinical applications. Methods: A collection of published work about 18 F-FDOPA PET was made and a critical review was discussed and written. Results: A number of research papers have been published demonstrating that in conjunction with MRI, 18 F-FDOPA PET provides greater sensitivity and specificity than these modalities in detection, grading, prognosis and validation of treatment success in both primary and recurrent gliomas. In further comparisons with 11 C-MET, 18 F-FLT, 18 F-FET and MRI, 18 F-FDOPA has shown similar or better efficacy. Recently synthesis cassettes have become available, making 18 F-FDOPA more accessible. Conclusions: According to the available data, 18 F-FDOPA PET is a viable radiotracer for imaging and treatment planning of gliomas. Advances in knowledge and implication for patient care: 18 F-FDOPA PET appears to be a viable radiopharmaceutical for the diagnosis and treatment planning of gliomas cases, improving on that of MRI and 18 F-FDG PET

On the synthesis of radiofluorinated amino acids by isotope exchange based on the example of 6-[{sup 18}F]Fluor-L-DOPA; Zur Synthese radiofluorierter aromatischer Aminosaeuren mittels Isotopenaustausch am Beispiel von 6-[{sup 18}F]Fluor-L-DOPA

Energy Technology Data Exchange (ETDEWEB)

Wagner, F M

2008-06-15

In nuclear medical diagnosis, 6-[{sup 18}F]fluoro-L-3,4-dihydroxyphenylalanine (6-[{sup 18}F]fluoro-LDOPA), an analogue of L-DOPA, is one of the few established radiopharmaceuticals used for the in vivo investigation of the presynaptic dopaminergic metabolism and of some kind of tumours via Positron Emission Tomography (PET). The presently used method of preparation of the radiotracer by electrophilic labelling is limited to low amounts of activity at high costs. Known nucleophilic syntheses, however, result either in insufficient enantiomeric purity or the known multi-step syntheses are hard to automate, due to their complexity. During this work a novel, easy to automate alternative for the preparation of 6-[{sup 18}F]fluoro-L-DOPA, was developed and evaluated, using a direct nucleophilic {sup 18}F-fluorination of a protected amino acid derivative. The resulting product has a very high enantiomeric purity. At first, the general suitability of the (S)-BOC-BMI-derivatives for the synthesis of {sup 18}F-labelled amino acids, used in this work, was investigated using a less complex precursor, which resulted in the amino acid 6-[{sup 18}F]fluoro-L-m-tyrosin via acidic hydrolysis. The preparation of a useful precursor for the nucleophilic {sup 18}F-isotope substitution, namely the (2S,5S)-tert.-butyl- 5-(2-fluoro-5-formylbenzyl)-2-tert.-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate, was investigated in three general different ways. At first it was tried to obtain this product via formylation after coupling with the BOC-BMI, secondly via {alpha},{beta}-dehydro amino acid derivatives and finally via a systematic multi-step synthesis. Only the last mentioned way resulted in a precursor with sufficient purity that could be labelled. The radiochemical yield of the isotopic exchange was about 60 %. In the next step, the presented concept was modified to synthesize a precursor for the preparation of 6-[{sup 18}F]fluoro-L-DOPA. Only a combination of the protecting groups

[18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery.

Science.gov (United States)

Rasul, Sazan; Hartenbach, Sabrina; Rebhan, Katharina; Göllner, Adelina; Karanikas, Georgios; Mayerhoefer, Marius; Mazal, Peter; Hacker, Marcus; Hartenbach, Markus

2018-05-15

Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [ 18 F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

Automated striatal uptake analysis of 18F-FDOPA PET images applied to Parkinson's disease patients

International Nuclear Information System (INIS)

Chang Icheng; Lue Kunhan; Hsieh Hungjen; Liu Shuhsin; Kao, Chinhao K.

2011-01-01

6-[ 18 F]Fluoro-L-DOPA (FDOPA) is a radiopharmaceutical valuable for assessing the presynaptic dopaminergic function when used with positron emission tomography (PET). More specifically, the striatal-to-occipital ratio (SOR) of FDOPA uptake images has been extensively used as a quantitative parameter in these PET studies. Our aim was to develop an easy, automated method capable of performing objective analysis of SOR in FDOPA PET images of Parkinson's disease (PD) patients. Brain images from FDOPA PET studies of 21 patients with PD and 6 healthy subjects were included in our automated striatal analyses. Images of each individual were spatially normalized into an FDOPA template. Subsequently, the image slice with the highest level of basal ganglia activity was chosen among the series of normalized images. Also, the immediate preceding and following slices of the chosen image were then selected. Finally, the summation of these three images was used to quantify and calculate the SOR values. The results obtained by automated analysis were compared with manual analysis by a trained and experienced image processing technologist. The SOR values obtained from the automated analysis had a good agreement and high correlation with manual analysis. The differences in caudate, putamen, and striatum were -0.023, -0.029, and -0.025, respectively; correlation coefficients 0.961, 0.957, and 0.972, respectively. We have successfully developed a method for automated striatal uptake analysis of FDOPA PET images. There was no significant difference between the SOR values obtained from this method and using manual analysis. Yet it is an unbiased time-saving and cost-effective program and easy to implement on a personal computer. (author)

Chemical consequences resulting from multi-millicurie preparation of 6-[18F]-fluoro-6-deoxy-L-ascorbic acid

International Nuclear Information System (INIS)

Kothari, P.J.; Finn, R.D.; Bornmann, W.G.; Agus, D.B.; Vera, J.C.; Larson, S.M.

1997-01-01

Ascorbic acid is required for human physiology and is particularly important in maintaining normal connective tissue and host defense. Our interest in this carboxylic acid stems from its similarity in transport with glucose in human cells. In order to investigate these phenomena, we report a refined synthesis of 6-[ 18 F]-fluoro-6-deoxy-L-ascorbic acid ( 18 F-FAA) via nucleophilic displacement of the cyclic sulfate with Kryptofix 2.2.2/K 18 F complex which results in multi-millicurie quantities of high specific activity product. The trace carrier-added synthesis has resulted in a decay corrected radiochemical yield of 31.6±3.4% with a specific activity approaching 180 mCi/μmol. Our preliminary experience with the assessment of the chemical stability of both the radiolabelled and stable product is also presented. (orig.)

Aspects of 6-[18F]fluoro-L-DOPA preparation: precursor synthesis, preparative HPLC purification and determination of radiochemical purity

International Nuclear Information System (INIS)

Fuechtner, F.; Angelberger, P.; Kvaternik, H.; Hammerschmidt, F.; Simovc, B. Peric; Steinbach, J.

2002-01-01

A modified method for the synthesis of the intermediate product N-Boc-3,4-di(Boc-O)-6-iodo-L-phenylalanine ethyl ester of the [ 18 F]FDOPA precursor preparation was developed. With the application of bis-(trifluoroacetoxy)-iodobenzene for the iodination step with elemental iodine the yield of the intermediate can be increased from 12% to 50-60%. By replacing silica-gel-based RP HPLC column by a polymer-based column for semi-preparative purification of [ 18 F]FDOPA from the reaction mixture the radiochemical purity of the final product can be increased up to >99%. For the determination of the radiochemical impurity [ 18 F]fluoride a HPLC method using a column with polymer-based RP material was introduced

New PET tracers for cerebral dopamine: Should 6-[18f]fluoro-dopa be replaced?

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Chen, J.J.; Murthy, D.; Nahmias, C.; Garnett, E.S.

1993-01-01

The visualization with PET of dopaminergic terminals in the human brain has been accomplished by a variety of approaches using β + -labelled substrates 1. for Aromatic L-Amino acid Decarboxylase, AADC, (6-[ 18 F]fluoro-L-dopa, FD; 6-[ 18 F]fluoro-L-meta-tyrosine, FmT; L-[ 11 C]Dopa); and β + -labelled inhibitors 2. for reuptake transporter ([ 11 C]Cocain, [ 11 C]WIN 35,428); 3. for Monoamine Oxidase-B ([ 11 C]deprenyl); 4. for the Vesicular uptake site ([ 11 C]tetrabenzamine). The enzyme approach with FD has been particularly successful in providing important insights into Parkinson's disease and dystonias. The extraction of quantitative data from FD/PET studies in humans is complicated by the formation of O-methylFD in the periphery, which, like FD, also enters the brain. Following the suggestion by deJesus (1988) to use a labelled meta-tyrosine (substrate for AADC but not COMT) the authors have synthesized FmT, developed it into a radiopharmaceutical (toxicology and radiation dose in humans) and studied the intracerebral distribution in man and the metabolites in monkeys. They found that FmT's peripheral metabolite does not enter the brain. Unlike FD, FmT delineates with greater clarity the dopaminergic terminals and cells including those in the substantia nigra that, so far, could not be investigated with any other PET tracer. Thus, FmT appears to be superior to FD

Biodistribution and human dosimetry estimation of fluoro-L-DOPA as PET imaging agent of dopaminergic nerve transmitter systems

International Nuclear Information System (INIS)

Tang Ganghua; Wang Mingfang; Luo Lei; Gan Manquan; Tang Xiaolan; Zhang Lan; Wang Yongxian

2002-01-01

Objective: To investigate the biodistribution and human dosimetry estimation of 6-[ 18 F] Fluoro-L-DOPA (FDOPA). Methods: Biodistribution of FDOPA in normal rats and brain of hemi-Parkinsonism rats were determined. Human dosimetry estimation was performed by MIRD method based on the rats biodistribution data. Results: Biodistributions in normal rats showed high uptake in kidney, blood, striatum and hippocampi, fast clearance of radioactivity from kidney and blood, longer retain time in striatum and hippocampi, and higher striatum to cerebellum and striatum to cortex ratio. FDOPA uptake, striatum to cerebellum and striatum to cortex ratio in the lesioned side of hemi-Parkinsonism rats (P 2 to 2.3 x 10 -2 mGy/MBq and the effective dose in humans was estimated to be 2.05 x 10 -2 mSv/MBq after injection of FDOPA based on rats biodistribution data, which were consistent with those reported by literature on the whole. Conclusion: Human radiation dosimetry of FDOPA and other PET tracers can be estimated based on animals biodistribution data. The synthetic FDOPA is safe and efficient and can be used in animals, human and PD patients PET studies

Value of 18F-3,4-dihydroxyphenylalanine PET/MR image fusion in pediatric supratentorial infiltrative astrocytomas: a prospective pilot study.

Science.gov (United States)

Morana, Giovanni; Piccardo, Arnoldo; Milanaccio, Claudia; Puntoni, Matteo; Nozza, Paolo; Cama, Armando; Zefiro, Daniele; Cabria, Massimo; Rossi, Andrea; Garrè, Maria Luisa

2014-05-01

Infiltrative astrocytomas (IAs) represent a group of astrocytic gliomas ranging from low-grade to highly malignant, characterized by diffuse invasion of the brain parenchyma. When compared with their adult counterpart, pediatric IAs may be considered biologically distinct entities; nevertheless, similarly to those in adults they represent a complex oncologic challenge. The aim of this study was to investigate the diagnostic role, clinical contribution, and prognostic value of fused (18)F-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET/MR images in pediatric supratentorial IAs. Pediatric patients with supratentorial IAs involving at least 2 cerebral lobes, either newly diagnosed or with suspected disease progression, prospectively underwent (18)F-DOPA PET and conventional MR imaging, performed within 10 d of each other. (18)F-DOPA PET data were interpreted qualitatively and semiquantitatively, fusing images with MR images. PET scans were classified as positive if tumors identified on MR imaging exhibited tracer uptake above the level of the corresponding contralateral normal brain. Maximum standardized uptake values, tumor-to-normal contralateral tissue ratios, and tumor-to-normal striatum ratios were calculated for all tumors. Correlations between the degree and extent of (18)F-DOPA uptake, MR imaging tumor characteristics, and histologic results were investigated. The contribution of (18)F-DOPA PET/MR image fusion was considered relevant if it enabled one to select the most appropriate biopsy site, discriminate between disease progression and treatment-related changes, or influence treatment strategy. The patient's outcome was finally correlated with (18)F-DOPA uptake. Thirteen patients (8 boys and 5 girls) were included (5 diffuse astrocytomas, 2 anaplastic astrocytomas, 5 gliomatosis cerebri, and 1 glioblastoma multiforme). The (18)F-DOPA uptake pattern was heterogeneous in all positive scans (9/13), revealing metabolic heterogeneities within each tumor. Significant

Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent gliomas.

Science.gov (United States)

Youland, Ryan S; Pafundi, Deanna H; Brinkmann, Debra H; Lowe, Val J; Morris, Jonathan M; Kemp, Bradley J; Hunt, Christopher H; Giannini, Caterina; Parney, Ian F; Laack, Nadia N

2018-05-01

Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M-P- in 16%, M-P+ in 32%, M+P+ in 46% and M+P- in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.

The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

1992-12-01

The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1992-12-01

The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

Guideline for PET/CT imaging of neuroendocrine neoplasms with {sup 68}Ga-DOTA-conjugated somatostatin receptor targeting peptides and {sup 18}F-DOPA

Energy Technology Data Exchange (ETDEWEB)

Bozkurt, Murat Fani [Hacettepe University Faculty of Medicine Department of Nuclear Medicine, Ankara (Turkey); Virgolini, Irene; Decristoforo, Clemens [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Balogova, Sona [Comenius University and St. Elisabeth Oncology Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Tenon Hospital AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Beheshti, Mohsen [St. Vincent' s Hospital, PET-CT Center, Department of Nuclear Medicine and Endocrinology, Linz (Austria); Paracelsus Medical University, Department of Nuclear Medicine, Salzburg (Austria); Rubello, Domenico [Santa Maria della Misericordia Hospital, Department of Nuclear Medicine, PET Center and Medical Physics and Radiology, Rovigo (Italy); Ambrosini, Valentina; Fanti, Stefano [University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna (Italy); Kjaer, Andreas [National University Hospital and University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Delgado-Bolton, Roberto [San Pedro Hospital and Centre for Biomedical Research of La Rioja (CIBIR), Department of Diagnostic Imaging (Radiology) and Nuclear Medicine, Logrono (Spain); Kunikowska, Jolanta [Medical University of Warsaw, Nuclear Medicine, Warsaw (Poland); Oyen, Wim J.G. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London (United Kingdom); Chiti, Arturo [Humanitas University, Nuclear Medicine Department, Rozzano, MI (Italy); Giammarile, Francesco [University of Lyon, Nuclear Medicine, Lyon (France)

2017-08-15

Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using {sup 68}Ga-DOTA-conjugated peptides, as well as {sup 18}F-DOPA imaging for various neuroendocrine neoplasms. The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with {sup 68}Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts. (orig.)

On the synthesis of radiofluorinated amino acids by isotope exchange based on the example of 6-[18F]Fluor-L-DOPA

International Nuclear Information System (INIS)

Wagner, F.M.

2008-06-01

In nuclear medical diagnosis, 6-[ 18 F]fluoro-L-3,4-dihydroxyphenylalanine (6-[ 18 F]fluoro-LDOPA), an analogue of L-DOPA, is one of the few established radiopharmaceuticals used for the in vivo investigation of the presynaptic dopaminergic metabolism and of some kind of tumours via Positron Emission Tomography (PET). The presently used method of preparation of the radiotracer by electrophilic labelling is limited to low amounts of activity at high costs. Known nucleophilic syntheses, however, result either in insufficient enantiomeric purity or the known multi-step syntheses are hard to automate, due to their complexity. During this work a novel, easy to automate alternative for the preparation of 6-[ 18 F]fluoro-L-DOPA, was developed and evaluated, using a direct nucleophilic 18 F-fluorination of a protected amino acid derivative. The resulting product has a very high enantiomeric purity. At first, the general suitability of the (S)-BOC-BMI-derivatives for the synthesis of 18 F-labelled amino acids, used in this work, was investigated using a less complex precursor, which resulted in the amino acid 6-[ 18 F]fluoro-L-m-tyrosin via acidic hydrolysis. The preparation of a useful precursor for the nucleophilic 18 F-isotope substitution, namely the (2S,5S)-tert.-butyl- 5-(2-fluoro-5-formylbenzyl)-2-tert. -butyl-3-methyl-4-oxoimidazolidine-1-carbox= yl ate, was investigated in three general different ways. At first it was tried to obtain this product via formylation after coupling with the BOC-BMI, secondly via α,β-dehydro amino acid derivatives and finally via a systematic multi-step synthesis. Only the last mentioned way resulted in a precursor with sufficient purity that could be labelled. The radiochemical yield of the isotopic exchange was about 60 %. In the next step, the presented concept was modified to synthesize a precursor for the preparation of 6-[ 18 F]fluoro-L-DOPA. Only a combination of the protecting groups benzyl and THP resulted in the useful

Characterization of glial tumors in PET/CT 18F-dopa and in perfusion MRI

International Nuclear Information System (INIS)

Nioche, Christophe

2011-01-01

MRI provides morphological information about a tumour, as well as information regarding its micro-vascularisation of the tumour. In PET/CT, accumulation of 18 F-Dopa in tumour cells results from the metabolic activity greater than that of healthy tissues.We studied 28 gliomas for which we analysed data from MRI and PET/CT. A registration method has been developed to combine information from both PET and MRI and to extract volumes of interest consistent with the information included in the two modalities. In these volumes, the tumour compartment and normal tissue compartment were identified using a Gaussian mixture model. Parameters from PET or MRI data were then calculated in these compartments. ROC analyses combined with linear discriminant analyses were used to assess whether joint observation of standardized uptake value (SUVmax) and relative Cerebral Blood Volume (rCBV) or of relative rk1 and rCBV could distinguish between low grade and high grade tumours. We found that using this joint analysis, 82% of high-grade tumors and 70% of low grade tumors were correctly classified (AUC of 0.88 for [SUVmax, rCBV] and of 0.92 for [rk1, rCBV]). Considering the combined information from [SUVmax, rCBV], the sensitivity for detecting high-grade tumors was 95% with a specificity of 60%. The negative predictive value was 52% for a positive predictive value of 95%. Similarly, considering the combined information from [rk1, rCBV], we also obtain a specificity of 60% associated with a 95% sensitivity for detecting high-grade tumors, with a negative predictive value of 60% and positive predictive value of 95%. Our work shows that joint analysis of information from microvascular and metabolic is possible by combining PET and MR imaging data. However, we found that, in our patient population, the microvascular information obtained through MR did not achieve better discrimination than the metabolic information derived from PET only. (author)

Automated image registration for FDOPA PET studies

International Nuclear Information System (INIS)

Kang-Ping Lin; Sung-Cheng Huang, Dan-Chu Yu; Melega, W.; Barrio, J.R.; Phelps, M.E.

1996-01-01

In this study, various image registration methods are investigated for their suitability for registration of L-6-[18F]-fluoro-DOPA (FDOPA) PET images. Five different optimization criteria including sum of absolute difference (SAD), mean square difference (MSD), cross-correlation coefficient (CC), standard deviation of pixel ratio (SDPR), and stochastic sign change (SSC) were implemented and Powell's algorithm was used to optimize the criteria. The optimization criteria were calculated either unidirectionally (i.e. only evaluating the criteria for comparing the resliced image 1 with the original image 2) or bidirectionally (i.e. averaging the criteria for comparing the resliced image 1 with the original image 2 and those for the sliced image 2 with the original image 1). Monkey FDOPA images taken at various known orientations were used to evaluate the accuracy of different methods. A set of human FDOPA dynamic images was used to investigate the ability of the methods for correcting subject movement. It was found that a large improvement in performance resulted when bidirectional rather than unidirectional criteria were used. Overall, the SAD, MSD and SDPR methods were found to be comparable in performance and were suitable for registering FDOPA images. The MSD method gave more adequate results for frame-to-frame image registration for correcting subject movement during a dynamic FDOPA study. The utility of the registration method is further demonstrated by registering FDOPA images in monkeys before and after amphetamine injection to reveal more clearly the changes in spatial distribution of FDOPA due to the drug intervention. (author)

FDOPA-(18F: a PET radiopharmaceutical recently registered for diagnostic use in countries of the European Union

Directory of Open Access Journals (Sweden)

Yanna-Marina Chevalme

2007-09-01

Full Text Available Positron emission tomography (PET and its recent update PET/CT are very effective diagnostic tools for non-invasive imaging of metabolic or functional disorders in target tissues. The clinical usefulness of fluorodeoxyglucose-(18F (FDG has been now widely accepted. Recently, the clinical usefulness of fluoroDOPA-(18F or FDOPA, an aminoacid labelled with the same positron emitter fluorine-18, has been evaluated and recognised in France and subsequently in several EU countries. FDOPA is diagnostic PET agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinson's disease, and more recently to detect, stage and restage neuroendocrine tumours and to search for recurrence of viable glioma tissue. The present article summarises the body of evidence that led the French Medicines Agency (AFSSAPS to grant a marketing authorisation to IASOdopa, a commercial preparation of FDOPA. Brief case reports and figures illustrate the diagnostic performance of FDOPA PET or PET/CT in the different settings that are currently approved in oncology.Tomografia por emissão de positrons (PET e sua recente atualização PET/CT são ferramentas de diagnóstico muito eficientes para imagens não invasivas de desordens metabólicas ou funcionais em tecido alvo. A utilidade clínica da fluordesoxiglicose-(18F(FDG tem sido agora largamente aceita. Recentemente, a utilidade clinica de fluoroDOPA-(18F ou FDOPA, um aminoácido marcado com o mesmo emissor de pósitron, flúor-18, tem sido avaliado e reconhecido na França e subsequentemente em alguns países da União Européia. FDOPA é o radiofármaco para diagnóstico em PET, o qual tem sido usado por décadas para obtenção de imagens da perda de neurônios dopaminérgicos na doença de Parkinson e, mais recentemente, para identificar inicialmente o estágio e a reavaliação de tumores neuroendócrinos e para a pesquisa da recorrência de glioma viável. O presente artigo resume o conjunto

Estimation of patient dose in 18 F-FDG and 18 F-FDOPA PET/CT examinations

Directory of Open Access Journals (Sweden)

Aruna Kaushik

2013-01-01

Full Text Available Purpose: To estimate specific organ and effective doses to patients resulting from the 18 F-FDG ( 18 F-2-deoxy-D-glucose and 18 F-FDOPA (6-fluoro-( 18 F-L-3, 4-dihydroxyphenylalanine PET/CT examinations for whole body and brain. Materials and Methods: Three protocols for whole body and three for brain PET/CT were used. The CTDI values were measured using standard head and body CT phantoms and also computed using a software CT-Expo for dose evaluation from the CT component. OLINDA software based on MIRD method was used for estimating doses from the PET component of the PET/CT examination. Results: The organ doses from 18 F-FDG and 18 F-FDOPA whole body and brain PET/CT studies were estimated. The total effective dose from a typical protocol of whole body PET/CT examination was 14.4 mSv for females and 11.8 mSv for male patients from 18 F-FDG, whereas it was 11 mSv for female and 9.1 mSv for male patients from 18 F-FDOPA. The total effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv for females and 5.1 mSv for males from 18 F-FDG whereas it was 3.7 mSv for females and 2.8 mSv for males from 18 F-FDOPA. Conclusions: The effective radiation doses from whole body PET/CT examination was approximately 4-8 times higher than the background radiation dose from both 18 F-FDG and 18 F-FDOPA scans, while it was 1-3 times the background radiation dose from PET/CT scans of brain.

Impact of L-DOPA treatment on regional cerebral blood flow and metabolism in the basal ganglia in a rat model of Parkinson's disease.

Science.gov (United States)

Ohlin, K Elisabet; Sebastianutto, Irene; Adkins, Chris E; Lundblad, Cornelia; Lockman, Paul R; Cenci, M Angela

2012-05-15

Large increases in regional cerebral blood flow (rCBF) have been measured in patients with Parkinson's disease (PD) following the administration of L-DOPA, but the underlying mechanisms have remained unknown. In this study, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were used to compare patterns of rCBF and regional cerebral glucose utilisation (rCGU) in chronically L-DOPA-treated subjects following a final injection of L-DOPA or saline. The same animal model was used to the leakage of a blood-brain barrier (BBB) tracer molecule at 60 min vs. 24h following the last L-DOPA injection of a chronic treatment. All the parameters under investigation were examined with brain autoradiography following intravenous injections of specific radiotracers in awake animals ([14C]-iodoantipyrine for rCBF, [14C]-2-deoxyglucose for rCGU, and [14C]-α-aminoisobutyric acid for BBB leakage). Significant changes in rCBF and rCGU on the side ipsilateral to the 6-OHDA lesion relative to the non-lesioned side were seen at 60 min ("ON") but not 24h ("OFF") following L-DOPA administration. These changes were not seen in sham-operated rats. In the output nuclei of the basal ganglia (the entopeduncular nucleus and the substantia nigra pars reticulata) both rCBF and rCGU were elevated both in acutely L-DOPA-treated rats and chronically L-DOPA-treated rats displaying dyskinesia, but did not change significantly in chronically L-DOPA-treated non-dyskinetic cases. Acutely and chronically L-DOPA-treated rats with dyskinesia exhibited increases in rCBF "ON L-DOPA" also in the motor cortex, the striatum, and the globus pallidus, but the corresponding changes in rCGU did not show the same direction, magnitude, and/or relative group differences. The uptake of a BBB tracer (studied in the striatum and the substantia nigra reticulata in chronically L-DOPA treated rats) was significantly higher ON vs. OFF L-DOPA. The present results are the first to show that the administration of L-DOPA is

Striatal kinetics of [11C]-(+)-nomifensine and 6-[18F]fluoro-L-dopa in Parkinson's disease measured with positron emission tomography

International Nuclear Information System (INIS)

Tedroff, J.; Aquilonius, S.-M.; Laihinen, A.; Rinne, U.; Hartvig, P.; Anderson, J.; Lundqvist, H.; Haaparanta, M.; Solin, O.; Antoni, G.; Gee, A.D.; Ulin, J.; Laangstroem, B.

1990-01-01

The kinetics in brain of the dopamine reuptake blocking agent [ 11 C]-(+)-nomifensine and the L-dopa analogue 6-[ 18 F]fluoro-L-dopa were compared in 3 patients with idopathic Parkinson's disease and agematched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nuclleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-[ 18 F]fluoro-L-dopa utilization and [ 11 C]-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinsons's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. (author)

Diagnostic performance of 18F-dihydroxyphenylalanine positron emission tomography in patients with paraganglioma: a meta-analysis

International Nuclear Information System (INIS)

Treglia, Giorgio; Cocciolillo, Fabrizio; Castaldi, Paola; Rufini, Vittoria; Giordano, Alessandro; De Waure, Chiara; Di Nardo, Francesco; Gualano, Maria Rosaria

2012-01-01

The aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of 18 F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG). A comprehensive computer literature search of studies published through 30 June 2011 regarding 18 F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of 18 F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 18 F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed. Eleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of 18 F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87-94%] on a per patient-based analysis and 79% (95% CI 76-81%) on a per lesion-based analysis. The pooled specificity of 18 F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86-99%) on a per patient-based analysis and 95% (95% CI 84-99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of 18 F-DOPA PET or PET/CT was found. A significant increase in sensitivity of 18 F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed. In patients with suspected PG 18 F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. 18 F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false-negative results should be kept in mind. Furthermore

Diagnostic performance of 18F-dihydroxyphenylalanine positron emission tomography in patients with paraganglioma: a meta-analysis.

Science.gov (United States)

Treglia, Giorgio; Cocciolillo, Fabrizio; de Waure, Chiara; Di Nardo, Francesco; Gualano, Maria Rosaria; Castaldi, Paola; Rufini, Vittoria; Giordano, Alessandro

2012-07-01

The aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of (18)F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG). A comprehensive computer literature search of studies published through 30 June 2011 regarding (18)F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of (18)F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of (18)F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed. Eleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of (18)F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87-94%] on a per patient-based analysis and 79% (95% CI 76-81%) on a per lesion-based analysis. The pooled specificity of (18)F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86-99%) on a per patient-based analysis and 95% (95% CI 84-99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of (18)F-DOPA PET or PET/CT was found. A significant increase in sensitivity of (18)F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed. In patients with suspected PG (18)F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. (18)F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false-negative results should be kept in mind

Diagnostic performance of {sup 18}F-dihydroxyphenylalanine positron emission tomography in patients with paraganglioma: a meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Treglia, Giorgio; Cocciolillo, Fabrizio; Castaldi, Paola; Rufini, Vittoria; Giordano, Alessandro [Catholic University of the Sacred Heart, Institute of Nuclear Medicine, Rome (Italy); De Waure, Chiara; Di Nardo, Francesco; Gualano, Maria Rosaria [Catholic University of the Sacred Heart, Institute of Hygiene, Rome (Italy)

2012-07-15

The aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of {sup 18}F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG). A comprehensive computer literature search of studies published through 30 June 2011 regarding {sup 18}F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of {sup 18}F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of {sup 18}F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed. Eleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of {sup 18}F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87-94%] on a per patient-based analysis and 79% (95% CI 76-81%) on a per lesion-based analysis. The pooled specificity of {sup 18}F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86-99%) on a per patient-based analysis and 95% (95% CI 84-99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of {sup 18}F-DOPA PET or PET/CT was found. A significant increase in sensitivity of {sup 18}F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed. In patients with suspected PG {sup 18}F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. {sup 18}F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false

Striatal kinetics of ( sup 11 C)-(+)-nomifensine and 6-( sup 18 F)fluoro-L-dopa in Parkinson's disease measured with positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Tedroff, J; Aquilonius, S -M [Department of Neurology, University Hospital (Sweden); Laihinen, A; Rinne, U [Department of Neurology, University of Turku (Finland); Hartvig, P [Department of Hospital Pharmacy, University Hospital (Sweden); Anderson, J [Department of Radiation Sciences, University Hospital (Sweden); Lundqvist, H [Svenberg Laboratory, Uppsala University (Sweden); Haaparanta, M; Solin, O [Medical Cyclotron Laboratory, University of Turku (Finland); Antoni, G; Gee, A D; Ulin, J; Laangstroem, B [Department of Organic Chemistry, University Hospital (Sweden)

1990-01-01

The kinetics in brain of the dopamine reuptake blocking agent ({sup 11}C)-(+)-nomifensine and the L-dopa analogue 6-({sup 18}F)fluoro-L-dopa were compared in 3 patients with idopathic Parkinson's disease and agematched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nuclleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-({sup 18}F)fluoro-L-dopa utilization and ({sup 11}C)-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinsons's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. (author).

18F-FDOPA PET/CT imaging of insulinoma revisited

International Nuclear Information System (INIS)

Imperiale, Alessio; Namer, Izzie-Jacques; Sebag, Frederic; Vix, Michel; Castinetti, Frederic; Kessler, Laurence; Moreau, Francois; Bachellier, Philippe; Guillet, Benjamin; Mundler, Olivier; Taieb, David

2015-01-01

18 F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to 18 F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with 18 F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using 18 F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after 18 F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after 18 F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. In the study group, 18 F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All 18 F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted 18 F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without CD premedication, eight patients), the final

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome

International Nuclear Information System (INIS)

Levine, Daniel S.; Nadel, Helen R.; Metzger, Daniel L.; Oviedo, Angelica; Adam, Michael J.; Skarsgard, Erik

2011-01-01

We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas. (orig.)

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome

Energy Technology Data Exchange (ETDEWEB)

Levine, Daniel S.; Nadel, Helen R. [University of British Columbia, Department of Radiology and Nuclear Medicine, British Columbia Children' s Hospital, Vancouver (Canada); Metzger, Daniel L. [University of British Columbia, Department of Pediatrics, Division of Endocrinology, British Columbia Children' s Hospital, Vancouver (Canada); Oviedo, Angelica [University of British Columbia, Department of Pathology, British Columbia Children' s Hospital, Vancouver (Canada); Adam, Michael J. [University of British Columbia, Department of PET Chemistry, Tri-University Meson Facility (TRIUMF), Vancouver (Canada); Skarsgard, Erik [University of British Columbia, Department of Surgery, British Columbia Children' s Hospital, Vancouver (Canada)

2011-10-15

We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas. (orig.)

No-carrier-added (NCA) synthesis of 6-[18F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6α, 8α, 8αβ)]-6,8-methano-2H-1,4-benzoxazin-2-one

International Nuclear Information System (INIS)

Horti, A.; Yale Univ., West Haven, CT; Redmond, D.E. Jr.; Soufer, R.

1995-01-01

3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6α,8α , 8αβ)]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[ 18 F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[ 18 F]fluorobenzaldehyde (1a) or 6-[ 18 F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [ 18 F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3α,6α,8α,8αβ)]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [ 18 F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3α, 6α, 8α8αβ)]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[ 18 F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/μmol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[ 18 F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[ 18 F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author)

No-carrier-added (NCA) synthesis of 6-[{sup 18}F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6{alpha}, 8{alpha}, 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one

Energy Technology Data Exchange (ETDEWEB)

Horti, A. [Yale Univ., New Haven, CT (United States). School of Medicine]|[Yale Univ., West Haven, CT (United States). PET Center; Redmond, D.E. Jr. [Yale Univ., New Haven, CT (United States). School of Medicine; Soufer, R. [Yale Univ., West Haven, CT (United States). PET Center

1995-12-31

3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6{alpha},8{alpha} , 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[{sup 18}F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[{sup 18}F]fluorobenzaldehyde (1a) or 6-[{sup 18}F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [{sup 18}F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3{alpha},6{alpha},8{alpha},8{alpha}{beta})]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [{sup 18}F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3{alpha}, 6{alpha}, 8{alpha}8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[{sup 18}F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/{mu}mol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[{sup 18}F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[{sup 18}F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author).

Positron emission tomography in degenerative disorders of the dopaminergic system

Energy Technology Data Exchange (ETDEWEB)

Karbe, H; Holthoff, V; Huber, M; Herholz, K; Wienhard, K; Wagner, R; Heiss, W D [Universitaetsklinik fuer Neurologie und Max-Planck-Institut fuer neurologische Forschung, Koeln (Germany)

1992-01-01

21 patients who had Parkinson's disease (PD), PD plus dementia of Alzheimer type (PDAT) or progressive supranuclear palsy (PSP), were studied with positron emission tomography (PET) using ({sup 18}F)-2-fluoro-2-deoxy-D-glucose (FDG). In one patient with strictly unilateral PD side differences in striatal dopa uptake were studied with 6-({sup 18}F)fluoro-L-dopa (F-dopa). In patients with PD PET with FDG did not show any significant change in regional cerebral metabolic rates for glucose (rCMR(Glu)). In PDAT glucose metabolism was generally reduced, the most severe decrease was found in parietal cortex. The metabolic pattern was similar to that typically found in patients with Alzheimer's disease (AD). In the patient with strictly unilateral PD rCMR(Glu) was normal, F-dopa PET, however, revealed a distinct reduction of dopa uptake in the contralateral putamen. In PSP glucose metabolism was significantly decreased in subcortical regions (caudatum, putamen and brainstem) and in frontal cortex. Thus PET demonstrated a clear difference of metabolic pattern between PDAT and PSP. (authors).

{sup 18}F-FDOPA PET/CT imaging of insulinoma revisited

Energy Technology Data Exchange (ETDEWEB)

Imperiale, Alessio; Namer, Izzie-Jacques [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); University of Strasbourg/CNRS and FMTS, Faculty of Medicine, ICube - UMR 7357, Strasbourg (France); Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, La Timone University Hospital, Marseille (France); Vix, Michel [University of Strasbourg, Department of General, Digestive, and Endocrine Surgery, IRCAD-IHU, Strasbourg (France); Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Diabetes and Metabolic Disorders, La Timone University Hospital, Marseille (France); Kessler, Laurence; Moreau, Francois [University of Strasbourg, Department of Diabetology, University Hospital of Strasbourg, Strasbourg (France); Bachellier, Philippe [University Hospitals of Strasbourg, Department of Visceral Surgery and Transplantation, Strasbourg (France); Guillet, Benjamin; Mundler, Olivier [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France); Aix-Marseille University, Biophysics and Nuclear Medecine, La Timone University Hospital, European Center for Research in Medical Imaging, Marseille (France)

2014-11-01

{sup 18}F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to {sup 18}F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with {sup 18}F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using {sup 18}F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after {sup 18}F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after {sup 18}F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. In the study group, {sup 18}F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All {sup 18}F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted {sup 18}F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without

Basal ganglia disorders studied by positron emission tomography

International Nuclear Information System (INIS)

Shinotoh, Hitoshi

1994-01-01

Recent development of positron emitting radioligands has made it possible to investigate the alterations of neurotransmitter systems associated with basal ganglia disorders in vivo. The functional integrity of nigro-striatal dopaminergic terminals may be studied with [ 18 F]6-fluoro-L-dopa ([ 18 F]dopa), and striatal dopamine receptor density with suitable PET ligands. [ 18 F]dopa uptake in the striatum (putamen) is markedly reduced in patients with Parkinson's disease (PD). [ 18 F]dopa-PET is capable of detecting sub-clinical nigral dysfunction in asymptomatic patients with familial PD and those who become Parkinsonian on conventional doses of dopamine receptor antagonists. While putamen [ 18 F]dopa uptake is reduced to a similar level in patients with multiple system atrophy (MSA) and PD, caudate [ 18 F] dopa uptake is lower in MSA than PD. However, [ 18 F]dopa PET cannot consistently distinguish MSA from PD because individual ranges of caudate [ 18 F]dopa uptake overlap. D 1 and D 2 receptor binding is markedly reduced in the striatum (posterior putamen) of MSA patients. Therefore, dopamine receptor imaging is useful for the differential diagnosis of MSA and PD. Similar marked reductions in putamen and caudate [ 18 F]dopa uptake have been observed in patients with progressive supranuclear palsy (PSP). Moderate reductions in D 2 receptor binding have been reported in the striatum of PSP patients. The reduction in D 2 receptor binding is more prominent in the caudate than putamen. Striatal [ 18 F]dopa uptake is normal or only mildly reduced in patients with dopa responsive dystonia (DRD). D 2 receptor binding is markedly reduced in patients with Huntington's disease, while striatal [ 18 F]dopa uptake is normal or mildly reduced. In summary, PET can demonstrate characteristic patterns of disruption of dopaminergic systems associated with basal ganglia disorders. These PET findings are useful in the differential diagnosis of basal ganglia disorders. (J.P.N.) 55 refs

Basal ganglia disorders studied by positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Shinotoh, Hitoshi [Chiba Univ. (Japan). School of Medicine

1994-04-01

Recent development of positron emitting radioligands has made it possible to investigate the alterations of neurotransmitter systems associated with basal ganglia disorders in vivo. The functional integrity of nigro-striatal dopaminergic terminals may be studied with [[sup 18]F]6-fluoro-L-dopa ([[sup 18]F]dopa), and striatal dopamine receptor density with suitable PET ligands. [[sup 18]F]dopa uptake in the striatum (putamen) is markedly reduced in patients with Parkinson's disease (PD). [[sup 18]F]dopa-PET is capable of detecting sub-clinical nigral dysfunction in asymptomatic patients with familial PD and those who become Parkinsonian on conventional doses of dopamine receptor antagonists. While putamen [[sup 18]F]dopa uptake is reduced to a similar level in patients with multiple system atrophy (MSA) and PD, caudate [[sup 18]F] dopa uptake is lower in MSA than PD. However, [[sup 18]F]dopa PET cannot consistently distinguish MSA from PD because individual ranges of caudate [[sup 18]F]dopa uptake overlap. D[sub 1] and D[sub 2] receptor binding is markedly reduced in the striatum (posterior putamen) of MSA patients. Therefore, dopamine receptor imaging is useful for the differential diagnosis of MSA and PD. Similar marked reductions in putamen and caudate [[sup 18]F]dopa uptake have been observed in patients with progressive supranuclear palsy (PSP). Moderate reductions in D[sub 2] receptor binding have been reported in the striatum of PSP patients. The reduction in D[sub 2] receptor binding is more prominent in the caudate than putamen. Striatal [[sup 18]F]dopa uptake is normal or only mildly reduced in patients with dopa responsive dystonia (DRD). D[sub 2] receptor binding is markedly reduced in patients with Huntington's disease, while striatal [[sup 18]F]dopa uptake is normal or mildly reduced. In summary, PET can demonstrate characteristic patterns of disruption of dopaminergic systems associated with basal ganglia disorders. (J.P.N.) 55 refs.

18F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L

International Nuclear Information System (INIS)

Feral, Chloe C.; Tissot, Floriane S.; Tosello, Lionel; Fakhry, Nicolas; Sebag, Frederic; Pacak, Karel; Taieb, David

2017-01-01

F-FDOPA is a highly sensitive and specific radiopharmaceutical for pheochromocytoma and paraganglioma (PPGL) imaging. However, 18 F-FDOPA might be falsely negative in these tumors, especially those related to mutations in succinate dehydrogenase genes (SDHx). The aim of the present study was to evaluate the relationship between expression of L-DOPA transporters and 18 F-FDOPA PET imaging results in PPGL. From 2007 to 2015, 175 patients with non-metastatic PPGL were evaluated by 18 F-FDOPA PET/CT for initial diagnosis/staging and follow-up. 18 F-FDOPA PET/CT was considered as falsely negative for at least one lesion in 10/126 (8%) patients (two sporadic, six SDHD, two SDHB PPGLs). The mRNA and protein expression levels of CD98hc and LATs were evaluated in samples with different genetic backgrounds and imaging phenotypes. The qRT-PCR and immunohistochemical analyses were performed in 14 and 16 tumor samples, respectively. The SDHx mutated samples exhibited a significant decrease in mRNA expression of LAT3 when compared to sporadic PPGLs (P = 0.042). There was also a statistical trend toward decreased CD98hc (P = 0.147) and LAT4 (P = 0.012) levels in SDHx vs sporadic PPGLs. No difference was observed for LAT1/LAT2 mRNA levels. LAT1 protein was expressed in 15 out of 16 (93.75%) SDHx tumors, regardless of the 18 F-FDOPA positivity. LAT1 and CD98hc were co-expressed in 6/8 18 F-FDOPA-negative PPGLs. In contrast, in one case with absence of LAT1/CD98hc, 18 F-FDOPA uptake was positive and attributed to LAT4 expression. We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce 18 F-FDOPA uptake. (orig.)

Diagnostic performance of fluorine-18-dihydroxyphenylalanine positron emission tomography in diagnosing and localizing the focal form of congenital hyperinsulinism: a meta-analysis.

Science.gov (United States)

Treglia, Giorgio; Mirk, Paoletta; Giordano, Alessandro; Rufini, Vittoria

2012-11-01

We performed a meta-analysis on published data on the diagnostic performance of fluorine-18 dihydroxyphenylalanine ((18)F-DOPA) positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI). A comprehensive computer literature search of studies published up to 31 January 2012 regarding (18)F-DOPA PET or PET/CT in patients with CHI was performed. Pooled sensitivity and specificity, area under the ROC curve and diagnostic odds ratio (DOR) of (18)F-DOPA PET or PET/CT in diagnosing focal CHI were calculated. The localization accuracy of focal CHI was also estimated. Seven studies comprising 195 CHI patients were included. The pooled sensitivity and specificity of (18)F-DOPA PET or PET/CT in differentiating between focal and diffuse CHI were 89% (95% confidence interval [CI]:81-95%) and 98% (95% CI:89-100%), respectively. The DOR was 74.5 (95% CI:18-307). The area under the ROC curve was 0.95. The pooled accuracy of these functional imaging methods in localizing focal CHI was 80% (95% CI:71-88%). In CHI patients, (18)F-DOPA PET or PET/CT demonstrated high sensitivity and specificity in differentiating between focal and diffuse CHI. (18)F-DOPA PET or PET/CT are accurate methods of localizing focal CHI. Nevertheless, possible sources of false-negative results for focal CHI should be kept in mind.

Secondary parkinsonism due to focal substantia nigra lesions. A PET study with [18F]FDG and [18F]fluorodopa

International Nuclear Information System (INIS)

Boecker, H.; Weindl, A.; Kruggel, F.; Graerin v. Einsiedel, H.; Contrad, B.; Leenders, K.; Antonini, A.; Kuwert, T.

1996-01-01

We present a 71 year old woman with predominantly right sided parkinsonim of sudden onset, but without tremor. Magnetic resonance imaging (MRI) depicted lesions affecting the substantia nigra (SN) bilaterally, but more pronounced on the left side. There were no other discernible structural lesions. Using positron emission tomography (PET), we investigated regional cerebral metabolic rate of glucose (rCMRG) using the tracer [ 18 F]-fluorodeoxyglucose (FDG), and striatal dopa decarboxylase capacity using the tracer [ 18 F]-L-6-fluorodopa (FDOPA). The degree and pattern of distribution of FDOPA uptake reductions (putamen > caudate nuclei) were similar to those in idopathic Parkinson's disease (PD). FDG uptake also revealed similar changes (reductions in frontal cortex and cerebellum, but increases in thalamus), except for putamen which showed reduced rCMRG. In conclusion, the absence of tremor at rest accords with experimental SN lesions. The PET findings in this atypical condition are explained in terms of deafferentation of various brain regions involved in motor control. Furthermore, they illustrate the metabolic effects related to acute focal lesions of the SN as opposed to the progressive degeneration in idiopathic PD and may serve to help unravel the complicated pathophysiology underlying these conditions. (au) 39 refs

{sup 18}F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L

Energy Technology Data Exchange (ETDEWEB)

Feral, Chloe C.; Tissot, Floriane S.; Tosello, Lionel [INSERM U1081, Institute for Research on Cancer and Aging of Nice (IRCAN), Nice (France); Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Pacak, Karel [Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (United States); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France)

2017-05-15

F-FDOPA is a highly sensitive and specific radiopharmaceutical for pheochromocytoma and paraganglioma (PPGL) imaging. However, {sup 18}F-FDOPA might be falsely negative in these tumors, especially those related to mutations in succinate dehydrogenase genes (SDHx). The aim of the present study was to evaluate the relationship between expression of L-DOPA transporters and {sup 18}F-FDOPA PET imaging results in PPGL. From 2007 to 2015, 175 patients with non-metastatic PPGL were evaluated by {sup 18}F-FDOPA PET/CT for initial diagnosis/staging and follow-up. {sup 18}F-FDOPA PET/CT was considered as falsely negative for at least one lesion in 10/126 (8%) patients (two sporadic, six SDHD, two SDHB PPGLs). The mRNA and protein expression levels of CD98hc and LATs were evaluated in samples with different genetic backgrounds and imaging phenotypes. The qRT-PCR and immunohistochemical analyses were performed in 14 and 16 tumor samples, respectively. The SDHx mutated samples exhibited a significant decrease in mRNA expression of LAT3 when compared to sporadic PPGLs (P = 0.042). There was also a statistical trend toward decreased CD98hc (P = 0.147) and LAT4 (P = 0.012) levels in SDHx vs sporadic PPGLs. No difference was observed for LAT1/LAT2 mRNA levels. LAT1 protein was expressed in 15 out of 16 (93.75%) SDHx tumors, regardless of the {sup 18}F-FDOPA positivity. LAT1 and CD98hc were co-expressed in 6/8 {sup 18}F-FDOPA-negative PPGLs. In contrast, in one case with absence of LAT1/CD98hc, {sup 18}F-FDOPA uptake was positive and attributed to LAT4 expression. We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce {sup 18}F-FDOPA uptake. (orig.)

Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]traces, [11C/[18F]-HTP)

International Nuclear Information System (INIS)

Ambrosini, A.; Morgini, J.J.; Nanni, C.; Castellucci, P.; Fanti, S.

2015-01-01

Neuroendocrine neoplasms (NEN) functional imaging is an evolving field that witnessed major advances in the past two decades. The routine use of PET/CT with an array of new radiotracers to specifically study NEN resulted in an increase in lesions detection. Currently, PET radiopharmaceuticals for NEN imaging include both metabolic ([18F]DOPA, [18F]FDG, [11C]/[18F]-HTP) and receptor-mediated compounds ([68Ga]DOTA-peptides). Discussion is still on-going regarding the clinical setting that may benefit the most from the use of one tracer over the other. [68Ga]DOTA-peptides are accurate for the detection of well differentiated NEN and are increasingly employed. Moreover, providing data on somatostatin receptors expression on NEN cells, they represent a fundamental procedure to be performed before starting therapy, as well as to guide treatment, with either hot or cold somatostatin analogues. The easy and economic synthesis process also favours their clinical employment even in centres without an on-site cyclotron. [18F]DOPA is accurate for studying well differentiated tumours however the difficult and expensive synthesis have limited its clinical employment. It currently can be successfully used for imaging tumours with variable to low expression of SSR (medullary thyroid carcinoma, neuroblastoma, pheocromocytoma), that cannot be accurately studied with [68Ga]DOTA-peptides. [11C]/[18F]-HTP has also been proposed to image well differentiated NEN, on the basis of serotonin pathway activity, for which [11C]/[18F]-HTP can be used as precursor. However, although preliminary data are encouraging, the feasibility of its widespread clinical use is still under discussion, mainly limited by a complex synthesis process and more proven advantages over other currently employed compounds. This review aims to provide an overview of the current status and clinical application of PET tracers to image well differentiated NEN and to focus on the still open-issues of debate

Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease.

Science.gov (United States)

Bimpisidis, Zisis; Öberg, Carl M; Maslava, Natallia; Cenci, M Angela; Lundblad, Cornelia

2017-06-01

Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [ 14 C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [ 14 C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

18F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

International Nuclear Information System (INIS)

Ledezma, Carlos J.; Chen, Wei; Sai, Victor; Freitas, Bonnie; Cloughesy, Tim; Czernin, Johannes; Pope, Whitney

2009-01-01

Background and purpose: 18 F-FDOPA PET demonstrates higher sensitivity and specificity for gliomas than traditional [ 18 F] FDG PET imaging. However, PET provides limited anatomic localization. The purpose of this study was to determine whether 18 F-FDOPA PET/MRI fusion can provide precise anatomic localization of abnormal tracer uptake and how this activity corresponds to MR signal abnormality. Methods: Two groups of patients were analyzed. Group I consisted of 21 patients who underwent 18 F-FDOPA PET and MRI followed by craniotomy for tumor resection. Group II consisted of 70 patients with a pathological diagnosis of glioma that had 18 F-FDOPA PET and MRI but lacked additional pathologic follow-up. Fused 18 F-FDOPA PET and MRI images were analyzed for concordance and correlated with histopathologic data. Results: Fusion technology facilitated precise anatomical localization of 18 F-FDOPA activity. In group I, all 21 cases showed pathology-confirmed tumor. Of these, 18 F-FDOPA scans were positive in 9/10 (90%) previously unresected tumors, and 11/11 (100%) of recurrent tumors. Of the 70 patients in group II, concordance between MRI and 18 F-FDOPA was found in 49/54 (90.1%) of patients with sufficient follow-up; in the remaining 16 patients concordance could not be determined due to lack of follow-up. 18 F-FDOPA labeling was comparable in both high- and low-grade gliomas and identified both enhancing and non-enhancing tumor equally well. In some cases, 18 F-FDOPA activity preceded tumor detection on MRI. Conclusion: 18 F-FDOPA PET/MRI fusion provides precise anatomic localization of tracer uptake and labels enhancing and non-enhancing tumor well. In a small minority of cases, 18 F-FDOPA activity may identify tumor not visible on MRI.

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

Energy Technology Data Exchange (ETDEWEB)

Capuani, S. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy)], E-mail: silvia.capuani@roma1.infn.it; Gili, T. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy); Bozzali, M. [Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Russo, S. [Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London (United Kingdom); Porcari, P. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Cametti, C. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Muolo, M. [Department of Biological Science, University ' Rome III' , Viale G. Marconi 446, Rome (Italy); D' Amore, E. [Serv. Qual./Sicurezza Sperim. Anim., Istituto Superiore di Sanita, Rome (Italy); Maraviglia, B. [Enrico Fermi Center, Compendio Viminale, Rome (Italy); Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Lazzarino, G. [Laboratory of Biochemistry, Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania (Italy); Pastore, F.S. [Department of Neuroscience, Institute of Neurosurgery, University ' Tor Vergata' , Via Montpellier 1, Rome (Italy)

2009-07-15

One of the main limitations for BNCT effectiveness is the insufficient intake of {sup 10}B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

International Nuclear Information System (INIS)

Capuani, S.; Gili, T.; Bozzali, M.; Russo, S.; Porcari, P.; Cametti, C.; Muolo, M.; D'Amore, E.; Maraviglia, B.; Lazzarino, G.; Pastore, F.S.

2009-01-01

One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PET-CT

International Nuclear Information System (INIS)

Beheshti, Mohsen; Poecher, Sigrid; Vali, Reza; Nader, Michael; Langsteger, Werner; Waldenberger, Peter; Broinger, Gabriele; Kohlfuerst, Susanne; Pirich, Christian; Dralle, Henning

2009-01-01

The purpose of this prospective study was to compare the value of DOPA PET-CT with FDG PET-CT in the detection of malignant lesions in patients with medullary thyroid carcinoma (MTC). Twenty-six consecutive patients (10 men, 16 women, mean age 59 ± 14 years) with elevated calcitonin levels were evaluated in this prospective study. DOPA and FDG PET-CT modalities were performed within a maximum of 4 weeks (median 7 days) in all patients. The data were evaluated on a patient- and lesion-based analysis. The final diagnosis of positive PET lesions was based on histopathological findings and/or imaging follow-up studies (i.e., DOPA and/or FDG PET-CT) for at least 6 months (range 6-24 months). In 21 (21/26) patients at least one malignant lesion was detected by DOPA PET, while only 15 (15/26) patients showed abnormal FDG uptake. DOPA PET provided important additional information in the follow-up assessment in seven (27%) patients which changed the therapeutic management. The patient-based analysis of our data demonstrated a sensitivity of 81% for DOPA PET versus 58% for FDG PET, respectively. In four (4/26) postoperative patients DOPA and FDG PET-CT studies were negative in spite of elevated serum calcitonin and CEA levels as well as abnormal pentagastrin tests. Overall 59 pathological lesions with abnormal tracer uptake were seen on DOPA and/or FDG PET studies. In the final diagnosis 53 lesions proved to be malignant. DOPA PET correctly detected 94% (50/53) of malignant lesions, whereas only 62% (33/53) of malignant lesions were detected with FDG PET. DOPA PET-CT showed superior results to FDG PET-CT in the preoperative and follow-up assessment of MTC patients. Therefore, we recommend DOPA PET-CT as a one-stop diagnostic procedure to provide both functional and morphological data in order to select those patients who may benefit from (re-)operation with curative intent as well as guiding further surgical procedures. (orig.)

2-18F-fluoro-2-deoxyglucose positron emission tomography in delirium.

Science.gov (United States)

Haggstrom, Lucy R; Nelson, Julia A; Wegner, Eva A; Caplan, Gideon A

2017-11-01

Delirium is a common, serious, yet poorly understood syndrome. Growing evidence suggests cerebral metabolism is fundamentally disturbed; however, it has not been investigated using 2- 18 F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in delirium. This prospective study thus explored FDG PET patterns of cerebral glucose metabolism in older inpatients with delirium. A particular emphasis was on the posterior cingulate cortex (PCC), a key region for attention, which is a central feature of delirium. Delirium scans were compared with post-delirium scans using visual analysis and semi-quantitative analysis with NeuroQ; 13 participants (8 female, median 84 y) were scanned during delirium, and 6 scanned again after resolution. On visual analysis, cortical hypometabolism was evident in all participants during delirium (13/13), and improved with delirium resolution (6/6). Using NeuroQ, glucose metabolism was higher post-delirium in the whole brain and bilateral PCC compared to during delirium ( p delirium duration. This research found widespread, reversible cortical hypometabolism during delirium and PCC hypometabolism was associated with inattention during delirium.

Disturbed neural circuits in a subtype of chronic catatonic schizophrenia demonstrated by F-18-FDG-PET and F-18-DOPA-PET

International Nuclear Information System (INIS)

Lauer, M.; Beckmann, H.; Stoeber, G.; Schirrmeister, H.; Gerhard, A.; Ellitok, E.; Reske, S.N.

2001-01-01

Permanent verbal, visual scenic and coenaestetic hallucinations are the most prominent psychopathological symptoms aside from psychomotor disorders in speech-sluggish catatonia, a subtype of chronic catatonic schizophrenia according to Karl Leonhard. These continuous hallucinations serve as an excellent paradigm for the investigation of the assumed functional disturbances of cortical circuits in schizophrenia. Data from positron emission tomography (F-18-FDG-PET and F-18-DOPA-PET) from three patients with this rare phenotype were available (two cases of simple speech-sluggish catatonia, one case of a combined speech-prompt/speech-sluggish subtype) and were compared with a control collective. During their permanent hallucinations, all catatonic patients showed a clear bitemporal hypometabolism in the F-18-FDG-PET. Both patients with the simple speech-sluggish catatonia showed an additional bilateral thalamic hypermetabolism and an additional bilateral hypometabolism of the frontal cortex, especially on the left side. In contrast, the patient with the combined speech-prompt/speech-sluggish catatonia showed a bilateral thalamic hypo-metabolism combined with a bifrontal cortical hypermetabolism. However, the left/right ratio of the frontal cortex also showed a lateralization effect with a clear relative hypometabolism of the left frontal cortex. The F-18-DOPA-PET of both schizophrenic patients with simple speech-sluggish catatonia showed a normal F-18-DOPA storage in the striatum, whereas in the right putamen of the patient with the combined form a higher right/left ratio in F-DOPA storage was discernible, indicating an additional lateralized influence of the dopaminergic system in this subtype of chronic catatonic schizophrenia. (author)

A high 18F-FDOPA uptake is associated with a slow growth rate in diffuse Grade II-III gliomas.

Science.gov (United States)

Isal, Sibel; Gauchotte, Guillaume; Rech, Fabien; Blonski, Marie; Planel, Sophie; Chawki, Mohammad B; Karcher, Gilles; Marie, Pierre-Yves; Taillandier, Luc; Verger, Antoine

2018-04-01

In diffuse Grade II-III gliomas, a high 3,4-dihydroxy-6-( 18 F)-fluoro-L-phenylalanine ( 18 F-FDOPA) positron emission tomography (PET) uptake, with a standardized uptake value (SUV max )/contralateral brain tissue ratio greater than 1.8, was previously found to be consistently associated with the presence of an isocitrate dehydrogenase (IDH) mutation, whereas this mutation is typically associated with a better prognosis. This pilot study was aimed to ascertain the prognostic value of this high 18 F-FDOPA uptake in diffuse Grade II-III gliomas with regard to the velocity of diameter expansion (VDE), which represents an established landmark of better prognosis when below 4 mm per year. 20 patients (42 ± 10 years, 10 female) with newly-diagnosed diffuse Grade II-III gliomas (17 with IDH mutation) were retrospectively included. All had a 18 F-FDOPA PET, quantified with SUV max ratio, along with a serial MRI enabling VDE determination. SUV max ratio was above 1.8 in 5 patients (25%) all of whom had a VDE VDE <4 mm/year in the overall population (45 vs 0%, p = 0.04) and also in the subgroup of patients with IDH mutation (45 vs 0%, p = 0.10). This pilot study shows that in diffuse Grade II-III gliomas, a high 18 F-FDOPA uptake would be predictive of low tumour growth, with a different prognostic significance than IDH mutation. Advances in knowledge: 18 F-FDOPA PET in a single session imaging could have prognostic value in initial diagnosis of diffuse Grade II-III gliomas.

Factors affecting 18 F FDOPA standardized uptake value in patients with primary brain tumors after treatment

International Nuclear Information System (INIS)

Chiaravalloti, Agostino; Fiorentini, Alessandro; Villani, Veronica; Carapella, Carmine; Pace, Andrea; Di Pietro, Barbara; Di Russo, Carmen; Palumbo, Barbara; Floris, Roberto; Schillaci, Orazio

2015-01-01

Aim: To investigate the factors affecting 18 F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. Materials and methods: 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent 18 F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (± 42.27), 16.04 (± 29.08) and 28.62 (± 34.49) months respectively. Results: 18 F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. Conclusions: The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect 18 F FDOPA uptake

Induction of dopamine biosynthesis by l-DOPA in PC12 cells: implications of L-DOPA influx and cyclic AMP.

Science.gov (United States)

Jin, Chun Mei; Yang, Yoo Jung; Huang, Hai Shan; Lim, Sung Cil; Kai, Masaaki; Lee, Myung Koo

2008-09-04

The effects of 3,4-dihydroxyphenylalanine (l-DOPA) on dopamine biosynthesis and cytotoxicity were investigated in PC12 cells. l-DOPA treatment (20-200 microM) increased the levels of dopamine by 226%-504% after 3-6 h of treatment and enhanced the activities of tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase (AADC). l-DOPA (20-200 muM) treatment led to a 562%-937% increase in l-DOPA influx at 1 h, which inhibited the activity of TH, but not AADC, during the same period. The extracellular releases of dopamine were also increased by 231%-570% after treatment with 20 and 200 microM l-DOPA for 0.5-3 h. l-DOPA at a concentration of 100-200 microM, but not 20 microM, exerted apoptotic cytotoxicity towards PC12 cells for 24-48 h. l-DOPA (20-200 microM) increased the intracellular cyclic AMP levels by 318%-557% after 0.5-1 h in a concentration-dependent manner. However, the elevated cyclic AMP levels by l-DOPA could not protect against l-DOPA (100-200 microM)-induced cytotoxicity after 24-48 h. In addition, l-DOPA (20-200 microM)-induced increases in cyclic AMP and dopamine were significantly reduced by treatment with SCH23390 (dopamine D(1) receptor antagonist). The increased levels of dopamine by l-DOPA were also reduced by H89 (protein kinase A, PKA, inhibitor) and GF109203X (protein kinase C inhibitor); however, the reduction by GF109203X was not significant. l-DOPA at 20-200 microM stimulated the phosphorylation of PKA and cyclic AMP-response element binding protein and induced the biosynthesis of the TH protein. These results indicate that 20-200 microM l-DOPA induces dopamine biosynthesis by two pathways. One pathway involves l-DOPA directly entering the cells to convert dopamine through AADC activity (l-DOPA decarboxylation). The other pathway involves l-DOPA and/or released dopamine activating TH to enhance dopamine biosynthesis by the dopamine D(1) receptor-cyclic AMP-PKA signaling system (dopamine biosynthesis by TH).

Automated synthesis of n.c.a. [18F]FDOPA via nucleophilic aromatic substitution with [18F]fluoride

International Nuclear Information System (INIS)

Shen, B.; Ehrlichmann, W.; Uebele, M.; Machulla, H.-J.; Reischl, G.

2009-01-01

An improved, automated synthesis of [ 18 F]FDOPA including four synthetic steps (fluorination, reductive iodination, alkylation and hydrolysis) is reported with each step optimized individually. In a home-made automatic synthesizer, 9064±3076 MBq of [ 18 F]FDOPA were produced within 120 min from EOB (n=5). Radiochemical purity and enantiomeric excess were both ≥95%. Specific activity was ca. 50 GBq/μmol at EOS. This automatically operable synthesis is well suited for the multi-patient-dose routine production of n.c.a. [ 18 F]FDOPA.

Serotonergic modulation of receptor occupancy in rats treated with L-DOPA after unilateral 6-OHDA lesioning

DEFF Research Database (Denmark)

Nahimi, Adjmal; Høltzermann, Mette; Landau, Anne M.

2012-01-01

Recent studies suggest that l-3,4 dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID), a severe complication of conventional L-DOPA therapy of Parkinson's disease, may be caused by dopamine (DA) release originating in serotonergic neurons. To evaluate the in vivo effect of a 5-HT(1A) agonist...... [(±)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide, 8-OHDPAT] on the L-DOPA-induced increase in extracellular DA and decrease in [(11) C]raclopride binding in an animal model of advanced Parkinson's disease and LID, we measured extracellular DA in response to L-DOPA or a combination of L......-DOPA and the 5-HT(1A) agonist, 8-OHDPAT, with microdialysis, and determined [(11) C]raclopride binding to DA receptors, with micro-positron emission tomography, as the surrogate marker of DA release. Rats with unilateral 6-hydroxydopamine lesions had micro-positron emission tomography scans with [(11) C...

Diagnostic role of 18F-dihydroxyphenylalanine positron emission tomography in patients with congenital hyperinsulinism: a meta-analysis.

Science.gov (United States)

Yang, Jigang; Hao, Ruirui; Zhu, Xiaohua

2013-04-01

Studies have reported the applications of F-dihydroxyphenylalanine (F-DOPA) PET in patients with congenital hyperinsulinism (CHI). The aim of this study was to systematically review and perform a meta-analysis of published data on the diagnostic role of F-DOPA PET in patients with CHI. A comprehensive computer literature search of studies on F-DOPA PET or PET/computed tomography (CT) in patients with CHI was conducted. The pooled sensitivity and specificity of F-DOPA PET or PET/CT in patients with CHI were calculated. The area under the receiver-operating characteristic curve was calculated to measure the accuracy of F-DOPA PET or PET/CT in patients with CHI. Ten studies comprising 181 patients with CHI were included in this meta-analysis. The pooled sensitivity of F-DOPA PET and PET/CT in detecting CHI was 88% on a per-patient-based analysis. The pooled specificity of F-DOPA PET and PET/CT in demonstrating CHI was 79%. The area under the receiver-operating characteristic curve was 0.92 on a per-patient-based analysis. In patients with CHI, F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. F-DOPA PET and PET/CT are accurate methods for the diagnosis of CHI. Nevertheless, possible sources of false-positive and false-negative results should be kept in mind.

Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging.

Science.gov (United States)

Tang, Caihua; Nie, Dahong; Tang, Ganghua; Gao, Siyuan; Liu, Shaoyu; Wen, Fuhua; Tang, Xiaolan

2017-07-01

Several 11 C and 18 F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA) analogues have been used for neurologic and oncologic diseases, especially for brain tumors and neuroendocrine tumors PET imaging. However, 18 F-labeled N-substituted l-DOPA analogues have not been reported so far. In the current study, radiosynthesis and biological evaluation of a new 18 F-labeled l-DOPA analogue, N-(2-[ 18 F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine ([ 18 F]FPDOPA) for tumor PET imaging are performed. The synthesis of [ 18 F]FPDOPA was via a two-step reaction sequence from 4-nitrophenyl-2-[ 18 F]fluoropropionate ([ 18 F]NFP). The biodistribution of [ 18 F]FPDOPA was determined in normal Kunming mice. In vitro competitive inhibition and protein incorporation experiments were performed with SPC-A-1 lung adenocarcinoma cell lines. PET/CT studies of [ 18 F]FPDOPA were conducted in C6 rat glioma and SPC-A-1 human lung adenocarcinoma and H460 human large cell lung cancer-bearing nude mice. [ 18 F]FPDOPA was prepared with a decay-corrected radiochemical yield of 28±5% and a specific activity of 50±15GBq/μmol (n=10) within 125min. In vitro cell experiments showed that [ 18 F]FPDOPA uptake in SPC-A-1 cells was primarily transported through Na + -independent system L, with Na + -dependent system B 0,+ and system ASC partly involved in it. Biodistribution data in mice showed that renal-bladder route was the main excretory system of [ 18 F]FPDOPA. PET imaging demonstrated intense accumulation of [ 18 F]FPDOPA in several tumor xenografts, with (8.50±0.40)%ID/g in C6 glioma, (6.30±0.12)%ID/g in SPC-A-1 lung adenocarcinoma, and (6.50±0.10)%ID/g in H460 large cell lung cancer, respectively. A novel N-substituted 18 F-labeled L-DOPA analogue [ 18 F]FPDOPA is synthesized and evaluated in vitro and in vivo. The results support that [ 18 F]FPDOPA seems to be a potential PET tracer for tumor imaging, especially be a better potential PET tracer than [ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F

Gypenosides attenuate the development of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

Science.gov (United States)

Shin, Keon Sung; Zhao, Ting Ting; Park, Keun Hong; Park, Hyun Jin; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

2015-04-21

Gypenosides (GPS) and ethanol extract of Gynostemma pentaphyllum (GP-EX) show anxiolytic effects on affective disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD). Long-term administration of L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of severe motor side effects such as L-DOPA-induced-dyskinesia (LID) in PD. The present study investigated the effects of GPS and GP-EX on LID in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. Daily administration of L-DOPA (25 mg/kg) in the 6-OHDA-lesioned rat model of PD for 22 days induced expression of LID, which was determined by the body and locomotive AIMs scores and contralateral rotational behaviors. However, co-treatments of GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg) with L-DOPA significantly attenuated the development of LID without compromising the anti-parkinsonian effects of L-DOPA. In addition, the increases in ∆FosB expression and ERK1/2 phosphorylation in 6-OHDA-lesioned rats induced by L-DOPA administration were significantly reduced by co-treatment with GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg). These results suggest that GPS (25 and 50 mg/kg) and GP-EX (50 mg/kg) effectively attenuate the development of LID by modulating the biomarker activities of ∆FosB expression and ERK1/2 phosphorylation in the 6-OHDA-lesioned rat model of PD. GPS and GP-EX will be useful adjuvant therapeutics for LID in PD.

Brain kinetics of L-[β-11C]DOPA in humans studied by positron emission tomography

International Nuclear Information System (INIS)

Hartvig, P.; Agren, H.; Reibring, L.; Tedroff, J.; Bjurling, P.; Kihlberg, T.; Langstroem, B.

1991-01-01

The in vivo dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) labelled with 11 C in the β position has been used for positron emission tomography studies of L-DOPA utilization in the brain. The brain uptake and kinetics of L-[ 11 C]DOPA-derived radioactivity were studied in healthy male volunteers, and the specific utilization, i.e. decarboxylation rate of L-[ 11 C]DOPA in different brain areas, was quantified using a brain region devoid of specific L-[ 11 C]DOPA utilization as reference. Total uptake of L-[ 11 C]DOPA-derived radioactivity measured in the brain varied two- to three-fold between subjects, with highest radioactivity in the striatal region. Specific utilization of L-[ 11 C]DOPA radioactivity in the striatal region and in the prefrontal cortex varied twofold between subjects. No specific utilization was observed in other regions of the brain. The uptake of radioactivity in the brain increased dose-dependently with the simultaneous administration of unlabelled L-DOPA up to 10 mg. On the other hand, a decrease in brain radioactivity uptake was measured after pretreatment with 1 mg/kg oral L-DOPA, indicating competition for transport across the blood-brain barrier. Benserazide 0.5mg/kg orally increased somewhat the radioactivity uptake to the brain. None of these pharmacological perturbations demonstrated any clearcut effect on specific utilization of L-[ 11 C]DOPA. Thus, 11 C-labelled L-DOPA is introduced as an alternative to the well-established L-6-[ 18 F]fluoro-DOPA methodology in clinical studies on brain L-DOPA uptake and dopamine synthesis. (authors)

Influence of O-methylated metabolite penetrating the blood-brain barrier to estimation of dopamine synthesis capacity in human L-[β-(11)C]DOPA PET.

Science.gov (United States)

Matsubara, Keisuke; Ikoma, Yoko; Okada, Maki; Ibaraki, Masanobu; Suhara, Tetsuya; Kinoshita, Toshibumi; Ito, Hiroshi

2014-02-01

O-methyl metabolite (L-[β-(11)C]OMD) of (11)C-labeled L-3,4-dihydroxyphenylalanine (L-[β-(11)C]DOPA) can penetrate into brain tissue through the blood-brain barrier, and can complicate the estimation of dopamine synthesis capacity by positron emission tomography (PET) study with L-[β-(11)C]DOPA. We evaluated the impact of L-[β-(11)C]OMD on the estimation of the dopamine synthesis capacity in a human L-[β-(11)C]DOPA PET study. The metabolite correction with mathematical modeling of L-[β-(11)C]OMD kinetics in a reference region without decarboxylation and further metabolism, proposed by a previous [(18)F]FDOPA PET study, were implemented to estimate radioactivity of tissue L-[β-(11)C]OMD in 10 normal volunteers. The component of L-[β-(11)C]OMD in tissue time-activity curves (TACs) in 10 regions were subtracted by the estimated radioactivity of L-[β-(11)C]OMD. To evaluate the influence of omitting blood sampling and metabolite correction, relative dopamine synthesis rate (kref) was estimated by Gjedde-Patlak analysis with reference tissue input function, as well as the net dopamine synthesis rate (Ki) by Gjedde-Patlak analysis with the arterial input function and TAC without and with metabolite correction. Overestimation of Ki was observed without metabolite correction. However, the kref and Ki with metabolite correction were significantly correlated. These data suggest that the influence of L-[β-(11)C]OMD is minimal for the estimation of kref as dopamine synthesis capacity.

Tracers tor the investigation of cerebral presynaptic dopaminergic function with positron emission tomography

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

1991-01-01

Two pharmacologic concepts, open-quotes metabolic precursorsclose quotes and open-quotes enzyme inhibitorsclose quotes have been applied to the design of PET tracers for the metabolic aspects of the neurotransmitter dopamine. As the result, highly useful, positron-emitting radiotracers have been developed with which to visualize and measure the cerebral distribution and metabolism of dopaminergic neurons. Positron emitter-labeled DOPA, particularly 6-[ 18 F]fluoro-L-DOPA, is being used to obtain information about the neurochemical anatomy of the dopamine system, and potentially, the rate constant of dopamine biosynthesis. 6-[ 18 F]Fluoro-L- meta-tyrosine delineates the dopaminergic structures even better than 6-[ 18 F]fluoro-L-DOPA but cannot provide kinetic information about dopamine biosynthesis. The in vivo activity of the enzyme aromatic L-aminoacid decarboxylase and that of monoamine oxidase types A and B can be measured with a-fluoro-methyl-6-[ 18 F]fluoro-L-DOPA, [ 11 C]clorgyline and L-[ 11 C]deprenyl, respectively. Thus, neuropharmacologic investigations of human presynaptic dopamine pharmacology are now possible in vivo

Pengaruh Diameter Partikel Terhadap Konsentrasi L-Dopa, Kc Dan De Pada Ekstraksi L-Dopa Dari Biji Kara Benguk (Mucuna Pruriens Dc.

Directory of Open Access Journals (Sweden)

Eni Budiyati

2013-10-01

Full Text Available Mucuna pruriens (biji kara benguk merupakan tanaman penghasil bahan obat-obatan karena mengandung senyawa L-Dopa. Senyawa tersebut dapat digunakan untuk pengobatan penyakit gangguan syaraf, anti bisa ular, meningkatkan bobot dan kekuatan otot, vitalitas seksual pria, zat anti-aging dan obat cacing pada manusia. Penelitian ini bertujuan untuk mengekstraksi L- Dopa dari biji kara benguk dengan menggunakan pelarut air. Di samping itu, penelitian ini juga mengevaluasi pengaruh dari diameter partikel terhadap konsentrasi L- dopa hasil ekstraksi, koefisien transfer massa (kC, dan difusivitas efektif (De. Tahapan yang digunakan pada penelitian ini adalah, persiapan bahan baku, proses ekstraksi, dan analisis L-Dopa. Proses ekstraksi dilakukan dalam tangki yang dilengkapi dengan thermometer. Analisis L-Dopa dilakukan dengan dengan High Performance Liquid Chromatography (HPLC. Hasil penelitian menunjukkan bahwa semakin kecil diameter partikel maka konsentrasi L-Dopa terekstrak semakin besar. Konsentrasi tertinggi diperoleh pada diameter partikel 0,5 mm yaitu 1739,56 ppm. Nilai difusivitas efektif (De untuk variabel diameter partikel (0,5; 0,675; 2,18; dan 2,5 mm hampir sama yaitu 2,99.10–5 sampai 3,07.10–5 cm2/menit. Sedangkan nilai koefisien transfer massa (kC berbanding terbalik dengan diameter partikel. Nilai kC berkisar antara 2,83.10-2 sampai 3,98.10-2 g/cm2.menit. 

18F-FDOPA PET/CT-Guided Radiofrequency Ablation of Liver Metastases from Neuroendocrine Tumours: Technical Note on a Preliminary Experience

Energy Technology Data Exchange (ETDEWEB)

Cazzato, Roberto Luigi, E-mail: gigicazzato@hotmail.it; Garnon, Julien, E-mail: juleiengarnon@gmail.com [Nouvel Hôpital Civil (Hôpitaux Universitaires de Strasbourg, HUS), Department of Interventional Radiology (France); Ramamurthy, Nitin, E-mail: nitin-ramamurthy@hotmail.com [Norfolk and Norwich University Hospital, Department of Radiology (United Kingdom); Tsoumakidou, Georgia, E-mail: georgia.tsoumakidou@chru-strasbourg.fr [Nouvel Hôpital Civil (Hôpitaux Universitaires de Strasbourg, HUS), Department of Interventional Radiology (France); Imperiale, Alessio, E-mail: alessio.imperiale@chru-strasbourg.fr; Namer, Izzie Jacques, E-mail: izzie.jacques.namer@chru-strasbourg.fr [Hôpital de Hautepierre (Hôpitaux Universitaires de Strasbourg, HUS), Department of Biophysics and Nuclear Medicine (France); Bachellier, Philippe, E-mail: philippe.bachellier@chru-strasbourg.fr [Hôpital de Hautepierre (Hôpitaux Universitaires de Strasbourg, HUS), Hepato-Pancreato-Biliary Surgery and Liver Transplantation (France); Caudrelier, Jean, E-mail: jean.caudrelier@chru-strasbourg.fr; Rao, Pramod, E-mail: pramodrao@me.com; Koch, Guillaume, E-mail: guillaume.koch@chru-strasbourg.fr; Gangi, Afshin, E-mail: gangi@unistra.fr [Nouvel Hôpital Civil (Hôpitaux Universitaires de Strasbourg, HUS), Department of Interventional Radiology (France)

2016-09-15

AimTo review our preliminary experience with 6-l-18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT-guided radiofrequency ablation (RFA) of liver metastases from neuroendocrine tumours (NETs).Materials and MethodsThree patients (mean age 51.3 years; range 43–56) with gastro-entero pancreatic NET (GEP-NET) liver metastases underwent 18F-FDOPA PET/CT-guided RFA. Patients were referred with oligometastatic hepatic-confined disease (1–6 metastases; <3 cm) on 18F-FDOPA PET/CT; poor lesion visualisation on US, CT, and MR; and ongoing symptoms. Procedures were performed in an interventional PET/CT scanner under general anaesthesia using a split-dose protocol. Lesion characteristics, procedural duration and technical success (accurate probe placement and post-procedural ablation-zone photopaenia), complications, patient and operator dose, and clinical outcomes were evaluated.ResultsThirteen liver metastases (mean size 11.4 mm, range 8–16) were treated in three patients (two presented with “carcinoid syndrome”). Technical success was 100 % with a mean procedural duration of 173.3 min (range 90–210) and no immediate complications. Mean patient dose was 2844 mGy·cm (range 2104–3686). Operator and radiographer doses were acceptable other than the operator’s right hand in the first case (149 µSv); this normalised in the second case. There was no local tumour or extra-hepatic disease progression at mid-term follow-up (mean 12.6 months; range 6–20); however, two cases progressed with new liver metastases at different sites. There was 100 % clinical success (n = 2) in resolving carcinoid syndrome symptoms.Conclusion18F-FDOPA PET/CT-guided RFA appears technically feasible, safe, and effective in patients with GEP-NETs and low-burden hepatic metastases. Further prospective studies are required to elucidate its precise role in tailored multimodality management of GEP-NET liver metastases.

Detection of preclinical Parkinson's disease with PET

International Nuclear Information System (INIS)

Brooks, D.J.

1991-01-01

Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to date. In addition, an intact sibling and a daughter of 1 of 4 siblings with PD both had low putamen 18F-dopa uptake. These preliminary findings suggest there may be a familial component to the etiology of PD. PET can also be used to detect underlying nigral pathology in patients with isolated tremor and patients who become rigid taking dopamine-receptor blocking agents (DRBAs). Patients with familial essential tremor have normal, and those with isolated rest tremor have consistently low, putamen 18F-dopa uptake. Drug-induced parkinsonism is infrequently associated with underlying nigral pathology

Interest of the PET with F DOPA in the exploration of endocrine para neoplastic syndromes (E.P.S.): about four cases; Interet de la TEP a la FDOPA dans l'exploration des syndromes paraneoplasiques endocriniens (SPE): a propos de 4 cas

Energy Technology Data Exchange (ETDEWEB)

Moreau Triby, C.; Pina, G.; Bournaud, C. [Centre de medecine nucleaire, groupement hospitalier Est, Lyon, (France); Billotey, C. [CERMEP, Lyon, (France); Raverot, G.; Borson Chazot, F. [service d' endocrinologie, groupement hospitalier Est, Lyon, (France)

2009-05-15

In front an ectopic secretion of adrenocorticotropic hormone (ACTH or corticotropin) or growth hormone (GH) the existence of an endocrine tumor must be evoked. The topographical diagnosis of these tumors is often difficult. The positron computed tomography with 6-fluoro-({sup 18}F)-L-dihydroxy-phenylalanine (PET-FDOPA) showed recently a good sensitivity in the detection of well differentiated endocrine tumors. We report our experience of the PET-FDOPA in the explorations of para-neoplasic endocrine syndromes. Our experience was relatively disappointing, this examination being a little contributive for our patients. The scintigraphy of receptors with somatostatin with octreoscan keeps all this place in this indication. (N.C.)

18F-FDOPA PET-CT vs 99mTc-GHA SPECT-CT in evaluation of recurrent brain gliomas

International Nuclear Information System (INIS)

Karunanithi, Sellam; Bal, C.; Malhotra, A.; Kumar, Abhishek; Bandopadhyay, G.P.; Gupta, D.

2010-01-01

Full text: Purpose of this study was to compare the role of 18 F-FDOPA PET-CT(FDOPA) and 99m Tc-GHA SPECT-CT (GHA) in detecting recurrence in glioma patients. Materials and Methods: Thirty patients of clinically suspected recurrent glioma of varying grades (ten with low grade and twenty with high grade primary tumor), previously treated with surgery and/or radiotherapy were evaluated using FDOPA and GHA. FDOPA images were interpreted positive for any abnormal tracer uptake noted in brain parenchyma. GHA images were interpreted as positive for abnormal tracer uptake noted in brain parenchyma. Final outcome was judged on the basis of biopsy report and/or clinical follow-up and serial MRI/MR spectroscopy imaging results. Results: Twenty- three patients were considered positive (death in 5, biopsy in 2, clinical progression in 6 and progression on imaging in 10) while 7 were negative for recurrence. FDOPA scan was positive in 22, negative in 8 patients. GHA was positive in 21, negative in 9 patients. Sensitivity, specificity, PPV and NPV of FDOPA were 95.6%, 100%, 100% and 87.5%, respectively. Sensitivity, specificity, PPV and NPV of GHA were 82.6%, 71.4%, 90.4% and 55.5%, respectively. Conclusions: FDOPA has the highest detection rate for recurrent glioma irrespective of the grade. FDOPA was found to be superior especially in detecting low grade viable gliomas. GHA, however due to high occurrence of false-positive results, prospective differentiation of recurrent tumor from treatment-induced changes is not possible in most patients

IDH mutation is paradoxically associated with higher {sup 18}F-FDOPA PET uptake in diffuse grade II and grade III gliomas

Energy Technology Data Exchange (ETDEWEB)

Verger, A. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Lorraine University, Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy, Nancy (France); Lorraine University, IADI, INSERM, UMR 947, Nancy (France); Metellus, P. [Centre Hospitalier Prive Clairval, Department of Neurosurgery, Marseille (France); Aix-Marseille University, INSERM, UMR 911, Marseille (France); Sala, Q. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Colin, C. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); Bialecki, E. [Centre Hospitalier Prive Clairval, Department of Neurosurgery, Marseille (France); Taieb, D. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Aix-Marseille University, CERIMED, Marseille (France); Chinot, O. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); APHM, La Timone Hospital, Department of Neuro-Oncology, Marseille (France); Figarella-Branger, D. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); APHM, La Timone Hospital, Department of Anatomopathology, Marseille (France); Guedj, E. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Aix-Marseille University, CERIMED, Marseille (France); Aix-Marseille University, Institut de Neurosciences de la Timone, CNRS, UMR 7289, Marseille (France); Hopital de la Timone, Service Central de Biophysique et Medecine Nucleaire, Marseille (France)

2017-08-15

The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and {sup 18}F-FDOPA uptake on PET in newly diagnosed gliomas. A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone {sup 18}F-FDOPA PET at an initial stage before surgery and histological diagnosis. {sup 18}F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). Patients with IDH mutation showed higher {sup 18}F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p < 0.05). This study showed paradoxically higher {sup 18}F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of {sup 18}F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation. (orig.)

18F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

International Nuclear Information System (INIS)

Piccardo, Arnoldo; Lopci, Egesta; Foppiani, Luca; Morana, Giovanni; Conte, Massimo

2014-01-01

Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. 123 I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established. 18 F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with 123 I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of 18 F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of 123 I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

The added value of [{sup 18}F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Maria-Joao; Bourgeois, Sandrine; Delzescaux, Thierry [Frederic Joliot Hospital, Biomedical Imaging Institute, Life Sciences Division, CEA, Orsay (France); Boddaert, Nathalie; Brunelle, Francis [Necker-Enfants Malades Hospital, AP-HP, Department of Radiology, Paris (France); Bellanne-Chantelot, Christine [Saint-Antoine Hospital, AP-HP, Department of Cytogenetics, Paris (France); Valayannopoulos, Vassili; Lonlay, Pascale de [Necker-Enfants Malades Hospital, AP-HP, Department of Pediatrics, Paris (France); Jaubert, Francis [Necker-Enfants Malades Hospital, AP-HP, Department of Pathology, Paris (France); Nihoul-Fekete, Claire [Necker-Enfants Malades Hospital, AP-HP, Department of Surgery, Paris (France)

2007-12-15

Neuroendocrine diseases are a heterogeneous group of entities with the ability to take up amine precursors, such as L-DOPA, and convert them into biogenic amines, such as dopamine. Congenital hyperinsulinism of infancy (HI) is a neuroendocrine disease secondary to either focal adenomatous hyperplasia or a diffuse abnormal pancreatic insulin secretion. While focal hyperinsulinism may be reversed by selective surgical resection, diffuse forms require near-total pancreatectomy when resistant to medical treatment. Here, we report the diagnostic value of PET with [{sup 18}F]fluoro-L-DOPA in distinguishing focal from diffuse HI. Forty-nine children were studied with [{sup 18}F]fluoro-L-DOPA. A thoraco-abdominal scan was acquired 45-65 min after the injection of 4.2 {+-} 1.0 MBq/kg of [{sup 18}F]fluoro-L-DOPA. Additionally, 12 of the 49 children were submitted to pancreatic venous catheterisation for blood samples (PVS) and 31 were also investigated using MRI. We identified abnormal focal pancreatic uptake of [{sup 18}F]fluoro-L-DOPA in 15 children, whereas diffuse radiotracer uptake was observed in the pancreatic area in the other 34 patients. In children studied with both PET and PVS, the results were concordant in 11/12 cases. All patients with focal radiotracer uptake and nine of the patients with diffuse pancreatic radiotracer accumulation, unresponsive to medical treatment, were submitted to surgery. In 21 of these 24 patients, the histopathological results confirmed the PET findings. In focal forms, selective surgery was followed by clinical remission without carbohydrate intolerance. These data demonstrate that PET with [{sup 18}F]fluoro-L-DOPA is an accurate non-invasive technique allowing differential diagnosis between focal and diffuse forms of HI. (orig.)

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

International Nuclear Information System (INIS)

Capuani, Silvia; Gili, Tommaso; Bozzali, Marco; Russo, Salvatore; Porcari, Paola; Cametti, Cesare; D'Amore, Emanuela; Colasanti, Marco; Venturini, Giorgio; Maraviglia, Bruno; Lazzarino, Giuseppe; Pastore, Francesco S.

2008-01-01

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10 B(n,α) 7 Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10 B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

Head-to-head comparison between "1"8F-FDOPA PET/CT and MR/CT angiography in clinically recurrent head and neck paragangliomas

International Nuclear Information System (INIS)

Heimburger, Celine; Hubele, Fabrice; Namer, Izzie Jacques; Veillon, Francis; Riehm, Sophie; Cavalcanti, Marcela; Taieb, David; Goichot, Bernard; Chabrier, Gerard; Petit-Thomas, Julie; Charpiot, Anne; Averous, Gerlinde; Imperiale, Alessio

2017-01-01

Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of "1"8F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up. Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both "1"8F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further "1"8F-FDOPA PET/CT and/or MRA. "1"8F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. "1"8F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. "1"8F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, "1"8F-FDOPA PET/CT detected two additional synchronous primary HNPGLs. "1"8F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that "1"8F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when "6"8Ga-labeled somatostatin analogues are

Manipulation of [C-11]-5-hydroxytryptophan and 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells

NARCIS (Netherlands)

Neels, Oliver C.; Koopmans, Klaas P.; Jager, Pieter L.; Vercauteren, Laya; van Waarde, Aren; Doorduin, Janine; Timmer-Bosscha, Hetty; Brouwers, Adrienne H.; de Vries, Elisabeth G. E.; Dierckx, Rudi A. J. O.; Kema, Ido P.; Elsinga, Philip H.

2008-01-01

[C-11]-5-Hydroxytryptophan ([C-11]HTP) and 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine [F-18]FDOPA) are used to image neuroendocrine tumors with positron emission tomography. The precise mechanism by which these tracers accumulate in tumor cells is unknown. We aimed to study tracer uptake via large

The relation of putamen nucleus 6-[18F]fluoro-L-m-tyrosine uptake to total Unified Parkinson's Disease Rating Scale scores

International Nuclear Information System (INIS)

Buchy, R.

2002-01-01

The contribution of dopaminergic deficiency in the striatum to the severity of locomotor disability in Parkinson's disease has been consistently shown with 6-[ 18 F]fluoro-L-DOPA in positron emission tomography. Recently, 6-[ 18 F]fluoro-L-m-tyrosine, an alternative tracer with similar distribution kinetics has been used to facilitate data analysis. Locomotor disability in Parkinson's disease can be measured using the Unified Parkinson's Disease Rating Scale. The Unified Parkinson's Disease Rating Scale was used in conjunction with 6-[ 18 F]fluoro-L-m-tyrosine -PET to clinically examine a group of five Parkinson's disease patients. An inverse relation similar to that previously demonstrated with 6-[ 18 F]fluoro-L-DOPA was found between the putamen nucleus 6-[ 18 F]fluoro-L-m-tyrosine influx constant and Unified Parkinson's Disease Rating Scale score. This finding suggests that like 6-[ 18 F]fluoro-L-m-tyrosine can be used to accurately measure the degree of locomotor disability caused by Parkinson's disease. (author)

Clinical Investigation of the Dopaminergic System with PET and FLUORINE-18-FLUORO-L-DOPA.

Science.gov (United States)

Oakes, Terrence Rayford

1995-01-01

Positron Emission Tomography (PET) is a tool that provides quantitative physiological information. It is valuable both in a clinical environment, where information is sought for an individual, and in a research environment, to answer more fundamental questions about physiology and disease states. PET is particularly attractive compared to other nuclear medicine imaging techniques in cases where the anatomical regions of interest are small or when true metabolic rate constants are required. One example with both of these requirements is the investigation of Parkinson's Disease, which is characterized as a presynaptic motor function deficit affecting the striatum. As dopaminergic neurons die, the ability of the striatum to affect motor function decreases. The extent of functional neuronal damage in the small sub-structures may be ascertained by measuring the ability of the caudate and putamen to trap and store dopamine, a neurotransmitter. PET is able to utilize a tracer of dopamine activity, ^ {18}F- scL-DOPA, to quantitate the viability of the striatum. This thesis work deals with implementing and optimizing the many different elements that compose a PET study of the dopaminergic system, including: radioisotope production; conversion of aqueous ^{18}F ^-into [^ {18}F]-F2; synthesis of ^{18}F- scL -DOPA; details of the PET scan itself; measurements to estimate the radiation dosimetry; accurate measurement of a plasma input function; and the quantitation of dopaminergic activity in normal human subjects as well as in Parkinson's Disease patients.

{sup 18}F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Lopci, Egesta [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Foppiani, Luca [Galliera Hospital, Internal Medicine and Endocrinology, Genoa (Italy); Morana, Giovanni [G. Gaslini Children' s Hospital, Department of Pathology and Radiology, Genoa (Italy); Conte, Massimo [G. Gaslini Children' s Hospital, Department of Hematology-Oncology, Genoa (Italy)

2014-03-15

Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. {sup 123}I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established.{sup 18}F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with {sup 123}I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of {sup 18}F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of {sup 123}I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

Radiosynthesis and pre-clinical evaluation of [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline

Energy Technology Data Exchange (ETDEWEB)

Smith, Graham [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Zhao Yongjun [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Leyton, Julius [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Shan Bo [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Nguyen, Quang-de; Perumal, Meg [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Turton, David [GE-Imanet, Hammersmith Hospital, Du Cane Road, London, W12 0NN (United Kingdom); Arstad, Erik; Luthra, Sajinder K.; Robins, Edward G. [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Aboagye, Eric O., E-mail: eric.aboagye@imperial.ac.u [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom)

2011-01-15

Introduction: Choline radiotracers are widely used for clinical PET diagnosis in oncology. [{sup 11}C]Choline finds particular utility in the imaging of brain and prostate tumor metabolic status, where 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ('FDG') shows high background uptake. More recently we have extended the clinical utility of [{sup 11}C]choline to breast cancer where radiotracer uptake correlates with tumor aggressiveness (grade). In the present study, a new choline analog, [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, was synthesized and evaluated as a potential PET imaging probe. Methods: [{sup 18}F]Fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were synthesized by alkylation of the relevant precursor with [{sup 18}F]fluorobromomethane or [{sup 18}F]fluoromethyl tosylate. Radiosynthesis of [{sup 18}F]fluoromethyl tosylate required extensive modification of the existing method. [{sup 18}F]Fluorocholine and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were then subjected to in vitro oxidative stability analysis in a chemical oxidation model using potassium permanganate and an enzymatic model using choline oxidase. The two radiotracers, together with the corresponding di-deuterated compound, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline, were then evaluated in vivo in a time-course biodistribution study in HCT-116 tumor-bearing mice. Results: Alkylation with [{sup 18}F]fluoromethyl tosylate proved to be the most reliable radiosynthetic route. Stability models indicate that [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline possesses increased chemical and enzymatic (choline oxidase) oxidative stability relative to [{sup 18}F]fluorocholine. The distribution of the three radiotracers, [{sup 18}F]fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, showed a similar uptake profile in most organs. Crucially, tumor uptake of [{sup 18}F]fluoro

Delayed O-methylation of l-DOPA in MB-COMT-deficient mice after oral administration of l-DOPA and carbidopa.

Science.gov (United States)

Tammimäki, Anne; Aonurm-Helm, Anu; Männistö, Pekka T

2018-04-01

1. Catechol-O-methyltransferase (COMT) is involved in the O-methylation of l-DOPA, dopamine, and other catechols. The enzyme is expressed in two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-COMT), which is anchored to intracellular membranes. 2. To obtain specific information on the functions of COMT isoforms, we studied how a complete MB-COMT deficiency affects the total COMT activity in the body, peripheral l-DOPA levels, and metabolism after l-DOPA (10 mg kg -1 ) plus carbidopa (30 mg kg -1 ) administration by gastric tube in wild-type (WT) and MB-COMT-deficient mice. l-DOPA and 3-O-methyl-l-DOPA (3-OMD) levels were assayed in plasma, duodenum, and liver. 3. We showed that the selective lack of MB-COMT did not alter the total COMT activity, COMT enzyme kinetics, l-DOPA levels, or the total O-methylation of l-DOPA but delayed production of 3-OMD in plasma and peripheral tissues.

Improved synthesis of 2'-deoxy-2'-[18F]-fluoro-1-β-D-arabinofuranosyl-5-iodouracil ([18F]-FIAU)

International Nuclear Information System (INIS)

Anderson, Harry; Pillarsetty, NagaVaraKishore; Cantorias, Melchor; Lewis, Jason S.

2010-01-01

An improved synthesis of 2'-[ 18 F]-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil ([ 18 F]-FIAU) has been developed. The method utilizes trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed coupling of 2-deoxy-2-[ 18 F]-fluoro-1,3,5-tri-O-benzoyl-D-arabinofuranose with 2,4-bis(trimethylsilyloxy)-5-iodouracil to yield the protected dibenzoyl-[ 18 F]-FIAU. Dibenzoyl-[ 18 F]-FIAU was deprotected with sodium methoxide to yield a mixture of α- and β-anomers in a ratio of 1:1, which were purified by HPLC. The procedure described in this article eliminates the need for HBr activation of the sugar prior to coupling with silylated iodouracil and is suitable for automation. The total reaction time was about 110 min, starting from [ 18 F]-fluoride. The average isolated yield of the required β-anomer was 10±6% (decay corrected) with average specific activity of 125 mCi/μmol.

Epimerisation of 2-[18F]-Fluoro-2-Deoxy-D-Glucose under alkaline conditions. A convenient method for the preparation of 2-[18F]-Fluoro-2-Deoxy-D-Mannose

International Nuclear Information System (INIS)

Varelis, P.

1998-01-01

Full text: The intended goal of our study into the epimerisation of 2-[ 18 F]- fluoro-2-deoxy-D-glucose ([ 18 F]-FDG) was to obtain 2-[ 18 F]-fluoro- 2-deoxy-D-mannose ([ 18 F]-FDM) for the purpose of both development and validation of our analytical methods used to determine the diastereoisomeric excess of [ 18 F]-FDG prepared in our facility. The epimerisation of [ 18 F]-FDG is smoothly effected by heating an aqueous solution of this radiochemical with 1 M aqueous sodium hydroxide at 50-60 deg C for 30 min, which provides an ∼ 1:1 mixture of [ 18 F]-FDG and [ 18 F]-FDM. In addition to the value of this mixture in analytical method development, we also found it useful for gauging the performance of the HPLC column used in the analysis of [ 18 F]-FDG. The aqueous sample matrix can be conveniently changed by azeotropic evaporation of the water with dry acetonitrile. In summary, the base catalysed epimerisation of 2-[ 18 F]-fluoro-2- deoxy-D-glucose provides a convenient and reliable procedure for the preparation 2-[ 18 F]-fluoro-2-deoxy-D-mannose, the stable analogue of which is not commercially available

Cerebrospinal Fluid Biomarkers For Parkinson's Disease and L-DOPA-induced Dyskinesia

DEFF Research Database (Denmark)

Dammann Andersen, Andreas

-DOPA, 18 patienter blev behandlet med L-DOPA, hvoraf 10 havde LID. Prøverne blev analyseret ved brug af high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), western blotting, enzyme linked immune-assays (ELISA), Multiplex og fluorescence-assays. Flere mulige......-patienter, som ikke fik L-DOPA. Patienter med LID havde signifikante forandringer i tryptofan- og katekolamin-metabolismen og en øget fosforylering af enzymet extracellular signal-regulated kinase (ERK 1/2). Disse fund kan bidrage til en bedre forståelse af de sygdomsmekanismer, som giver PS og LID...

Evaluation of blood-brain barrier transport and CNS drug metabolism in diseased and control brain after intravenous L-DOPA in a unilateral rat model of Parkinson's disease

Directory of Open Access Journals (Sweden)

Ravenstijn Paulien GM

2012-02-01

Full Text Available Abstract Background Changes in blood-brain barrier (BBB functionality have been implicated in Parkinson's disease. This study aimed to investigate BBB transport of L-DOPA transport in conjunction with its intra-brain conversion, in both control and diseased cerebral hemispheres in the unilateral rat rotenone model of Parkinson's disease. Methods In Lewis rats, at 14 days after unilateral infusion of rotenone into the medial forebrain bundle, L-DOPA was administered intravenously (10, 25 or 50 mg/kg. Serial blood samples and brain striatal microdialysates were analysed for L-DOPA, and the dopamine metabolites DOPAC and HVA. Ex-vivo brain tissue was analyzed for changes in tyrosine hydroxylase staining as a biomarker for Parkinson's disease severity. Data were analysed by population pharmacokinetic analysis (NONMEM to compare BBB transport of L-DOPA in conjunction with the conversion of L-DOPA into DOPAC and HVA, in control and diseased cerebral hemisphere. Results Plasma pharmacokinetics of L-DOPA could be described by a 3-compartmental model. In rotenone responders (71%, no difference in L-DOPA BBB transport was found between diseased and control cerebral hemisphere. However, in the diseased compared with the control side, basal microdialysate levels of DOPAC and HVA were substantially lower, whereas following L-DOPA administration their elimination rates were higher. Conclusions Parkinson's disease-like pathology, indicated by a huge reduction of tyrosine hydroxylase as well as by substantially reduced levels and higher elimination rates of DOPAC and HVA, does not result in changes in BBB transport of L-DOPA. Taking the results of this study and that of previous ones, it can be concluded that changes in BBB functionality are not a specific characteristic of Parkinson's disease, and cannot account for the decreased benefit of L-DOPA at later stages of Parkinson's disease.

5-(2-18F-fluoroethoxy)-L-tryptophan as a substrate of system L transport for tumor imaging by PET.

Science.gov (United States)

Krämer, Stefanie D; Mu, Linjing; Müller, Adrienne; Keller, Claudia; Kuznetsova, Olga F; Schweinsberg, Christian; Franck, Dominic; Müller, Cristina; Ross, Tobias L; Schibli, Roger; Ametamey, Simon M

2012-03-01

Large neutral l-amino acids are substrates of system L amino acid transporters. The level of one of these, LAT1, is increased in many tumors. Aromatic l-amino acids may also be substrates of aromatic l-amino acid decarboxylase (AADC), the level of which is enhanced in endocrine tumors. Increased amino acid uptake and subsequent decarboxylation result in the intracellular accumulation of the amino acid and its decarboxylation product. (18)F- and (11)C-labeled neutral aromatic amino acids, such as l-3,4-dihydroxy-6-(18)F-fluorophenylalanine ((18)F-FDOPA) and 5-hydroxy-l-[β-(11)C]tryptophan, are thus successfully used in PET to image endocrine tumors. However, 5-hydroxy-l-[β-(11)C]tryptophan has a relatively short physical half-life (20 min). In this work, we evaluated the in vitro and in vivo characteristics of the (18)F-labeled tryptophan analog 5-(2-(18)F-fluoroethoxy)-l-tryptophan ((18)F-l-FEHTP) as a PET probe for tumor imaging. (18)F-l-FEHTP was synthesized by no-carrier-added (18)F fluorination of 5-hydroxy-l-tryptophan. In vitro cell uptake and efflux of (18)F-l-FEHTP and (18)F-FDOPA were studied with NCI-H69 endocrine small cell lung cancer cells, PC-3 pseudoendocrine prostate cancer cells, and MDA-MB-231 exocrine breast cancer cells. Small-animal PET was performed with the respective xenograft-bearing mice. Tissues were analyzed for potential metabolites. (18)F-l-FEHTP specific activity and radiochemical purity were 50-150 GBq/μmol and greater than 95%, respectively. In vitro cell uptake of (18)F-l-FEHTP was between 48% and 113% of added radioactivity per milligram of protein within 60 min at 37°C and was blocked by greater than 95% in all tested cell lines by the LAT1/2 inhibitor 2-amino-2-norboranecarboxylic acid. (18)F-FDOPA uptake ranged from 26% to 53%/mg. PET studies revealed similar xenograft-to-reference tissue ratios for (18)F-l-FEHTP and (18)F-FDOPA at 30-45 min after injection. In contrast to the (18)F-FDOPA PET results, pretreatment with the

Evidence of D-phenylglycine as delivering tool for improving L-dopa absorption.

Science.gov (United States)

Wang, Chun-Li; Fan, Yang-Bin; Lu, Hsiao-Hwa; Tsai, Tung-Hu; Tsai, Ming-Cheng; Wang, Hui-Po

2010-09-06

L-dopa has been used for Parkinson's disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using D-phenylglycine to guard L-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1). D-phenylglycine was chemically attached on L-dopa to form D-phenylglycine-L-dopa as a dipeptide prodrug of L-dopa. The cross-membrane transport of this dipeptide and L-dopa via PepT1 was compared in brush-boarder membrane vesicle (BBMV) prepared from rat intestine. The intestinal absorption was compared by in situ jejunal perfusion in rats. The pharmacokinetics after i.v. and p.o. administration of both compounds were also compared in Wistar rats. The striatal dopamine released after i.v. administration of D-phenylglycine-L-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with (+)-methamphetamine (MA). The BBMV uptake of D-phenylglycine-L-dopa was inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but not by amino acids Phe or L-dopa. The cross-membrane permeability (Pm*) determined in rat jejunal perfusion of D-phenylglycine-L-dopa was higher than that of L-dopa (2.58 ± 0.14 vs. 0.94 ± 0.10). The oral bioavailability of D-phenylglycine-L-dopa was 31.7 times higher than that of L-dopa in rats. A sustained releasing profile of striatal dopamine was demonstrated after i. v. injection of D-phenylglycine-L-dopa (50 mg/kg), indicated that D-phenylglycine-L-dopa might be a prodrug of dopamine. D-phenylglycine-L-dopa was more efficient than L-dopa in lowering the rotation of unilateral striatal lesioned rats (19.1 ± 1.7% vs. 9.9 ± 1.4%). The BBMV uptake studies indicated that D-phenylglycine facilitated the transport of L-dopa through the intestinal

Evidence of d-phenylglycine as delivering tool for improving l-dopa absorption

Directory of Open Access Journals (Sweden)

Wang Chun-Li

2010-09-01

Full Text Available Abstract Background l-Dopa has been used for Parkinson's disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using d-phenylglycine to guard l-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1. Methods d-Phenylglycine was chemically attached on l-dopa to form d-phenylglycine-l-dopa as a dipeptide prodrug of l-dopa. The cross-membrane transport of this dipeptide and l-dopa via PepT1 was compared in brush-boarder membrane vesicle (BBMV prepared from rat intestine. The intestinal absorption was compared by in situ jejunal perfusion in rats. The pharmacokinetics after i.v. and p.o. administration of both compounds were also compared in Wistar rats. The striatal dopamine released after i.v. administration of d-phenylglycine-l-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with (+-methamphetamine (MA. Results The BBMV uptake of d-phenylglycine-l-dopa was inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but not by amino acids Phe or l-dopa. The cross-membrane permeability (Pm* determined in rat jejunal perfusion of d-phenylglycine-l-dopa was higher than that of l-dopa (2.58 ± 0.14 vs. 0.94 ± 0.10. The oral bioavailability of d-phenylglycine-l-dopa was 31.7 times higher than that of l-dopa in rats. A sustained releasing profile of striatal dopamine was demonstrated after i. v. injection of d-phenylglycine-l-dopa (50 mg/kg, indicated that d-phenylglycine-l-dopa might be a prodrug of dopamine. d-Phenylglycine-l-dopa was more efficient than l-dopa in lowering the rotation of unilateral striatal lesioned rats (19.1 ± 1.7% vs. 9.9 ± 1.4%. Conclusion The BBMV uptake studies indicated that d

Nociceptive Response to L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats.

Science.gov (United States)

Nascimento, G C; Bariotto-Dos-Santos, K; Leite-Panissi, C R A; Del-Bel, E A; Bortolanza, M

2018-04-02

Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating L-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease to a hind paw-induced persistent inflammation. Further, the effect of L-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by L-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. L-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of L-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.

Herbs containing L- Dopa: An update.

Science.gov (United States)

Ramya, Kuber B; Thaakur, Santhrani

2007-07-01

L-Dopa is the drug of choice in the treatment of Parkinson's disease but it has dose related adverse effects such as nausea, vomiting, orthostatic hypotension, end of dose deterioration, on off phenomena and on chronic therapy motor complications synonymous to parkinsonism. Mucuna pruriens (M.P) commonly known as velvet beans or cowitch are used in case of spasms associated with Parkins onism. Clinical efficacy of seeds of this plant was confirmed and the efficacy was contributed to its L-Dopa content. M.P extract showed twice the antiparkinsonism activity compared with synthetic L-Dopa. There is sufficient L-Dopa in broad bean (Vicia faba) pods. One study proved its efficacy in Parkinsonism. Ginkgo biloba extract showed protective effect in vivo and invitro. 50% ethanolic extract of Plumbago zeylanica was effective in rats. The following plants were reported to have L-Dopa but their protective effect is yet to be established in animal models. Vigna aconitifolia, Vigna unguiculata, Vigna vexillata, Prosopis chilensis, Pileostigma malabarica, Phanera vahlis, Parkinsonia acculeata, Macuna urens, Canvavalia glandiata, Cassia floribanda, Casia hirsute and Dalbergia retusa etc.

Evaluation of 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds

International Nuclear Information System (INIS)

Kim, Dong Hyun; Choe, Yearn Seong; Kim, Byung-Tae

2010-01-01

Click chemistry is a useful approach for the preparation of novel radiopharmaceuticals. In this study, we evaluated 4-[ 18 F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds. Our results showed that nucleophilic substitution of 4-tosyloxy-1-butyne with K[ 18 F]F produces vinyl acetylene as well as 4-[ 18 F]fluoro-1-butyne, while the same reaction using 5-tosyloxy-1-pentyne gives exclusively 5-[ 18 F]fluoro-1-pentyne. Thus, ω-[ 18 F]fluoro-1-alkynes with chain lengths longer than four carbons may be better radiolabeled synthons for use in click chemistry.

FDOPA-PET as a paradigm of molecular imaging in oncology

International Nuclear Information System (INIS)

Brink, I.; Hentschel, M.; Neumann, H.P.H.; Schaefer, O.; Moser, E.

2007-01-01

In recent years, positron emission tomography with 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) has become a wide-spread method in the diagnostics of Parkinson's disease. The amino acid is an important component in protein metabolism. As a precursor in the synthesis of catecholamines it is also of use in metabolic imaging of a variety, mostly neuroendocrine, tumors. The specific uptake mechanisms make FDOPA a paradigm of metabolic imaging. The current review assesses the value of the tracer in the diagnostics of different oncological diseases. It summarizes own experiences and the published results of oncological FDOPA PET-studies. Above all, there is a very high impact of FDOPA in the staging of pheochromocytomas and paragangliomas as well as serotonin-positive neuroendocrine tumors of the gastroentero-pancreatic system (NET-GEPs). Additionally, FDOPA extends the diagnostic possibilities in recurrent medullary thyroid cancer. In the imaging of tumors of the central nervous system, FDOPA represents an alternative to 11 C-labelled PET-tracers. First reports show a high accuracy in the differentiation of radiation induced necrosis and recurrent disease in both high and low grade brain tumors. Furthermore, there is a correlation between the uptake of FDOPA and the expression of proliferation markers. Today, the noninvasive differentiation of focal and diffuse congenital hyperinsulinism has therapeutic consequences. In cases of focal disease, the extent of pancreas resection can be limited resulting in better prognosis without diabetes mellitus. (orig.)

Aspergillus niger PA2: a novel strain for extracellular biotransformation of L-tyrosine into L-DOPA.

Science.gov (United States)

Agarwal, Pragati; Pareek, Nidhi; Dubey, Swati; Singh, Jyoti; Singh, R P

2016-05-01

L-DOPA (3,4-dihydroxyphenyl-L-alanine), an amino acid derivative is the most widely used drug of choice for the treatment of Parkinson's disease and other neurologic injuries. The present study deals with the elevated biochemical transformation of L-tyrosine to L-DOPA by Aspergillus niger PA2, a potent tyrosinase producer, isolated from decomposed food wastes. This appears to be the first report on A. niger as a notable extracellular tyrosinase producer. The extracellular tyrosinase activity produced remarkably higher levels of L-DOPA, i.e. 2.44 mg mL(-1) when the media was supplemented with 5 mg mL(-1) L-tyrosine. The optimum pH for tyrosinase production was 6.0, with the maximal L-DOPA production at the same pH. The product thus produced was analyzed by thin-layer chromatography, UV spectroscopy, high-performance liquid chromatography and Fourier transform infrared spectroscopy, that had denoted this to be L-DOPA. Kinetic parameters viz. Y p/s, Q s and Q p had further indicated the notable levels of production. Thus, Aspergillus niger PA2 could be a promising resource and may be further exploited for large-scale production of L-DOPA.

Overview on the biotechnological production of L-DOPA.

Science.gov (United States)

Min, Kyoungseon; Park, Kyungmoon; Park, Don-Hee; Yoo, Young Je

2015-01-01

L-DOPA (3,4-dihydroxyphenyl-L-alanine) has been widely used as a drug for Parkinson's disease caused by deficiency of the neurotransmitter dopamine. Since Monsanto developed the commercial process for L-DOPA synthesis for the first time, most of currently supplied L-DOPA has been produced by the asymmetric method, especially asymmetric hydrogenation. However, the asymmetric synthesis shows critical limitations such as a poor conversion rate and a low enantioselectivity. Accordingly, alternative biotechnological approaches have been researched for overcoming the shortcomings: microbial fermentation using microorganisms with tyrosinase, tyrosine phenol-lyase, or p-hydroxyphenylacetate 3-hydroxylase activity and enzymatic conversion by immobilized tyrosinase. Actually, Ajinomoto Co. Ltd commercialized Erwinia herbicola fermentation to produce L-DOPA from catechol. In addition, the electroenzymatic conversion system was recently introduced as a newly emerging scheme. In this review, we aim to not only overview the biotechnological L-DOPA production methods, but also to briefly compare and analyze their advantages and drawbacks. Furthermore, we suggest the future potential of biotechnological L-DOPA production as an industrial process.

Head-to-head comparison between {sup 18}F-FDOPA PET/CT and MR/CT angiography in clinically recurrent head and neck paragangliomas

Energy Technology Data Exchange (ETDEWEB)

Heimburger, Celine; Hubele, Fabrice; Namer, Izzie Jacques [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); CNRS/University of Strasbourg, ICube, UMR 7357, Strasbourg (France); University of Strasbourg, FMTS, Faculty of Medicine, Strasbourg (France); Veillon, Francis; Riehm, Sophie; Cavalcanti, Marcela [University Hospitals of Strasbourg, Department of Radiology, Strasbourg (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France); Goichot, Bernard; Chabrier, Gerard [University Hospitals of Strasbourg, Department of Internal Medicine, Strasbourg (France); Petit-Thomas, Julie; Charpiot, Anne [University Hospitals of Strasbourg, Department of Otolaryngology and Maxillofacial Surgery, Strasbourg (France); Averous, Gerlinde [University Hospitals of Strasbourg, Department of Pathology, Strasbourg (France); Imperiale, Alessio [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); CNRS/University of Strasbourg, ICube, UMR 7357, Strasbourg (France); University of Strasbourg, FMTS, Faculty of Medicine, Strasbourg (France); Hautepierre University Hospital, Biophysics and Nuclear Medicine, Strasbourg Cedex (France)

2017-06-15

Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of {sup 18}F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up. Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both {sup 18}F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further {sup 18}F-FDOPA PET/CT and/or MRA. {sup 18}F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. {sup 18}F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. {sup 18}F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, {sup 18}F-FDOPA PET/CT detected two additional synchronous primary HNPGLs. {sup 18}F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that {sup 18}F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when {sup 68

Biochemical Evidence of L-Dopa Synthesis in a Cytokine-Resilient Aspergillus oryzae

International Nuclear Information System (INIS)

Ali, S.; Saleem, R.

2016-01-01

The present work describes the microbiological production of 3,4 dihydroxy-L-phenylalanine (L-dopa) from a cytokine-inhibited mold culture of Aspergillus oryzae (strain Ck-R6). A level of 15 μg/ml cytokine was found optimal for culture resistance and better dopa-dopamine activity. Synthetic L-tyrosine was used as a basal carbon source. The aerobic reactions were carried out using pre-grown mycelia as a direct tyrosinase source. The mycelia were cultivated using 200 ml of GPY mineral-salt medium and developed at 30 degree C for 48 h (240 rpm) in 500 ml Erlenmeyer flasks. L-dopa production was found optimal when L-ascorbic acid (5 mg/ml) was added 6 min after starting the reaction (120 rpm). The maximal production (2.2 mg/ml L-dopa) was obtained when L-tyrosine concentration was 2.5 mg/ml. Mycelial level (75 mg/ml) and time of reaction (40 min) were also evaluated. L-Tyrosine consumption was found to be 2.1 mg/ml. After optimizing the reaction conditions, particularly L-ascorbic acid addition, a 30 percent improved L-dopa yield was achieved compared to control when the parameters including time of reaction (40 min), L-tyrosine concentration (2.5 mg/ml) and temperature (50 degree C) were optimized by two-factorial Plackett-Burman design (PBD). (author)

Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

International Nuclear Information System (INIS)

Fang, Chun-Kai; Chen, Hong-Wen; Wang, Wei-Hsun; Liu, Ren-Shen; Hwang, Jeng-Jong

2013-01-01

In this work, we used quantitative autoradiography to study the acute effect of cocaine, methamphetamine, and ketamine on the uptake of [ 18 F]FDOPA in the striatum of rats. Drugs were treated 0.5 h before (pre-treated), and 1.5 h after (post-treated) [ 18 F]FDOPA injections, rats were then sacrificed at 2 h post [ 18 F]FDOPA injections to determine the striatum/frontal cortex binding ratios in the striatum. The ratios were lower in the post-treated groups than those of the pre-treated groups, suggesting a net effect of inhibition of trapping of the tracer. The order of uptake inhibition is: ketamine>methamphetamine>cocaine

(18)F-Dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer : Relation to tumor differentiation

NARCIS (Netherlands)

Koopmans, Klaas P.; de Groot, Jan Willem B.; Plukker, John T. M.; de Vries, Elisabeth G. E.; Kema, Ido P.; Sluiter, Wim J.; Jager, Pieter L.; Links, Thera P.

Curative treatment for recurrent medullary thyroid cancer (MTC), diagnosed by rising serum calcitonin, is surgery, but tumor localization is difficult. Therefore, the value of (18)F-dihy-droxyphenylanaline PET ((18)F-DOPA PET), (18)F-FDG PET, (99m)Tc-V-di-mercaptosulfuricacid (DMSA-V) scintigraphy,

The effects of dopamine on regional cerebral blood flow in patients with Parkinson's disease before and after L-dopa. Measurement by Xe-enhanced CT

International Nuclear Information System (INIS)

Aiba, Ikuko; Indo, Toshikatsu; Takahashi, Akira.

1994-01-01

Regional cerebral blood flow (rCBF) was measured using the stable xenon enhanced CT method in previously untreated 13 patients with Parkinson's disease to evaluate CBF abnormality related to dysfunction of the nigrostriatal dopaminergic neurons. The patients comprised 5 men and 8 women with Hoehn-Yahr stage II-III. Age at onset ranged from 51 to 73 years (mean±SD, 61.8±8.9) and the duration of illness ranged from 1 to 96 months (15.1±24.1 months). In this series, there was no clinical evidence of hypertension, diabetes mellitus and cognitive impairment. rCBF was measured during 4-5-minutes inhalation, of 33% stable xenon gas-67% oxygen. The first measurement of rCBF was performed in all of the patients before L-dopa treatment. After initiation of L-dopa treatment (333.3±47.1 mg/day), the second measurement was carried out in 6 patients (1 man and 5 women) who had shown symptomatic improvement. The interval between both measurements was 57.7±16.9 days. The following results were obtained. 1) No significant CBF asymmetry was noted in any of the striatum, pallidum, thalamus, cerebrum, cerebellum and frontal lobe in untreated patients with Parkinson's disease. 2) After L-dopa treatment, rCBF was significantly increased only in the striatum as compared with the pretreatment level (51.9±9.3→63.1±9.9 ml/100g/min, p<0.01). 3) This increase was significantly greater on the more severely affected side (contralateral to the predominantly symptomatic limb) (p<0.05). These results suggest that the increase of rCBF in the striatum is closely related to functional improvement of the nigrostriatal dopaminergic neurons. (author)

L-DOPA is an endogenous ligand for OA1.

Directory of Open Access Journals (Sweden)

Vanessa M Lopez

2008-09-01

Full Text Available Albinism is a genetic defect characterized by a loss of pigmentation. The neurosensory retina, which is not pigmented, exhibits pathologic changes secondary to the loss of pigmentation in the retina pigment epithelium (RPE. How the loss of pigmentation in the RPE causes developmental defects in the adjacent neurosensory retina has not been determined, but offers a unique opportunity to investigate the interactions between these two important tissues. One of the genes that causes albinism encodes for an orphan GPCR (OA1 expressed only in pigmented cells, including the RPE. We investigated the function and signaling of OA1 in RPE and transfected cell lines. Our results indicate that OA1 is a selective L-DOPA receptor, with no measurable second messenger activity from two closely related compounds, tyrosine and dopamine. Radiolabeled ligand binding confirmed that OA1 exhibited a single, saturable binding site for L-DOPA. Dopamine competed with L-DOPA for the single OA1 binding site, suggesting it could function as an OA1 antagonist. OA1 response to L-DOPA was defined by several common measures of G-protein coupled receptor (GPCR activation, including influx of intracellular calcium and recruitment of beta-arrestin. Further, inhibition of tyrosinase, the enzyme that makes L-DOPA, resulted in decreased PEDF secretion by RPE. Further, stimulation of OA1 in RPE with L-DOPA resulted in increased PEDF secretion. Taken together, our results illustrate an autocrine loop between OA1 and tyrosinase linked through L-DOPA, and this loop includes the secretion of at least one very potent retinal neurotrophic factor. OA1 is a selective L-DOPA receptor whose downstream effects govern spatial patterning of the developing retina. Our results suggest that the retinal consequences of albinism caused by changes in melanin synthetic machinery may be treated by L-DOPA supplementation.

Management of L-dopa overdose in the competitive inhibition state

Directory of Open Access Journals (Sweden)

Hinz M

2014-07-01

Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole3 1Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3Cole Center for Healing, Cincinnati, OH, USA Abstract: The amino acid L-3,4-dihydroxyphenylalanine (L-dopa is prescribed for conditions where increased central and/or peripheral dopamine synthesis is desired. Its administration can establish dopamine concentrations higher than can be achieved from an optimal diet. Specific indications include Parkinson's disease and restless leg syndrome. The interaction between serotonin and dopamine exists in one of two distinctly different physiologic states: the endogenous state or the competitive inhibition state. Management with L-dopa in the competitive inhibition state is the focus of this paper. In the past, control of the competitive inhibition state was thought to be so difficult and complex that it was described in the literature as functionally “meaningless”. When administering L-dopa without simultaneous administration of serotonin precursors, the patient is in the endogenous state. Experience gained with patient outcomes during endogenous L-dopa administration does not allow predictability of L-dopa outcomes in the competitive inhibition state. The endogenous approach typically increases the daily L-dopa dosing value in a linear fashion until symptoms of Parkinson's disease are under control. It is the novel observations made during treatment with the competitive inhibition state approach that L-dopa dosing values above or below the optimal therapeutic range are generally associated with the presence of the exact same Parkinson's disease symptoms with identical intensity. This recognition requires a novel approach to optimization of daily L-dopa dosing values from that used in the endogenous state. This paper outlines that novel approach through utilization of a pill stop. This approach enhances patient safety through its ability to

Levodopa/benserazide microsphere (LBM) prevents L-dopa induced dyskinesia by inactivation of the DR1/PKA/P-tau pathway in 6-OHDA-lesioned Parkinson's rats.

Science.gov (United States)

Xie, Cheng-long; Wang, Wen-Wen; Zhang, Su-fang; Yuan, Ming-Lu; Che, Jun-Yi; Gan, Jing; Song, Lu; Yuan, Wei-En; Liu, Zhen-Guo

2014-12-16

L-3, 4-dihydroxyphenylalanine (L-dopa) is the gold standard for symptomatic treatment of Parkinson's disease (PD), but long-term therapy is associated with the emergence of L-dopa-induced dyskinesia (LID). In the present study, L-dopa and benserazide were loaded by poly (lactic-co-glycolic acid) microspheres (LBM), which can release levodopa and benserazide in a sustained manner in order to continuous stimulate dopaminergic receptors. We investigated the role of striatal DR1/PKA/P-tau signal transduction in the molecular event underlying LID in the 6-OHDA-lesioned rat model of PD. We found that animals rendered dyskinetic by L-dopa treatment, administration of LBM prevented the severity of AIM score, as well as improvement in motor function. Moreover, we also showed L-dopa elicits profound alterations in the activity of three LID molecular markers, namely DR1/PKA/P-tau (ser396). These modifications are totally prevented by LBM treatment, a similar way to achieve continuous dopaminergic delivery (CDD). In conclusion, our experiments provided evidence that intermittent administration of L-dopa, but not continuous delivery, and DR1/PKA/p-tau (ser396) activation played a critical role in the molecular and behavioural induction of LID in 6-OHDA-lesioned rats. In addition, LBM treatment prevented the development of LID by inhibiting the expression of DR1/PKA/p-tau, as well as PPEB mRNA in dyskintic rats.

Assessing local outcomes in heterogeneous gliomas

International Nuclear Information System (INIS)

Dowson, Nicholas; Bourgeat, Pierrick; Salvado, Olivier; Rose, Stephen; Thomas, Paul; Fay, Michael; Jeffree, Rosalind L; Winter, Craig; Coulthard, Alan; Smith, Jye; Gal, Yaniv; Crozier, Stuart

2014-01-01

Tumours are known to be heterogeneous, yet typical treatment plans consider them as a single unit. This may influence treatment outcomes. However, treatment cannot be customised to intra-tumour variation without a method to establish outcomes at an intra-tumour scale. This work proposes a method to both assess and measure outcomes locally within tumours. Methods: Four patients were scanned at two post-surgery time points using contrast enhanced MRI and 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET. The shell of active tumour tissue is divided into a set of small subregions at both time points. Local outcome is measured from changes in subregion volume over time. The utility of the proposed approach is evaluated by measuring the correlation between PET uptake and documented growth. Correlation with overall survival time was also examined. Results: Local outcomes were heterogeneous and evidence of a positive correlation between local 18F-DOPA uptake and local progression was observed. Conclusions: Given that intra-tumour outcomes are heterogeneous the consistently positive correlation between FDOPA uptake and progression, local analysis of tumours could prove useful for treatment planning.

Neuro degenerative diseases: clinical concerns; Les maladies neuro-degeneratives: problemes cliniques

Energy Technology Data Exchange (ETDEWEB)

Ibanez, V. [Hopitaux Universitaires de Geneve (HUG), Unite de Neuroimagerie, Dept. de Psychiatrie (Switzerland)

2005-04-15

Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [{sup 18}F]-deoxyglucose and [{sup 18}F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [{sup 18}F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [{sup 18}F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

Neuro degenerative diseases: clinical concerns

International Nuclear Information System (INIS)

Ibanez, V.

2005-01-01

Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [ 18 F]-deoxyglucose and [ 18 F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [ 18 F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [ 18 F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

Tumour imaging by Positron Emission Tomography using fluorinase generated 5-[18F]fluoro-5-deoxyribose as a novel tracer

International Nuclear Information System (INIS)

Dall'Angelo, Sergio; Bandaranayaka, Nouchali; Windhorst, Albert D.; Vugts, Danielle J.; Born, Dion van der; Onega, Mayca; Schweiger, Lutz F.; Zanda, Matteo; O'Hagan, David

2013-01-01

Introduction: 5-[ 18 F]Fluoro-5-deoxyribose ([ 18 F]FDR) 3 was prepared as a novel monosaccharide radiotracer in a two-step synthesis using the fluorinase, a C-F bond forming enzyme, and a nucleoside hydrolase. The resulting [ 18 F]FDR 3 was then explored as a radiotracer for imaging tumours (A431 human epithelial carcinoma) by positron emission tomography in a mice model. Methods: 5-[ 18 F]Fluoro-5-deoxyribose ([ 18 F]FDR) 3, was prepared by incubating S-adenosyl-L-methionine (SAM) and [ 18 F]fluoride with the fluorinase enzyme, and then incubating the product of this reaction, [ 18 F]-5'-fluoro-5'-deoxadenosine ([ 18 F]FDA) 2, with an adenosine hydrolase to generate [ 18 F]FDR 3. The enzymes were freeze-dried and were used on demand by dissolution in buffer solution. The resulting [ 18 F]FDR 3 was then administered to four mice that had tumours induced from the A431 human epithelial carcinoma cell line. Results: The tumour (A431 human epithelial carcinoma) bearing mice were successfully imaged with [ 18 F]FDR 3. The radiotracer displayed good tumour imaging resolution. A direct comparison of the uptake and efflux of [ 18 F]FDR 3 with 2-[ 18 F]fluoro-2-deoxyglucose ([ 18 F]FDG) was made, revealing comparative tumour uptake and imaging potential over the first 10–20 min. The study revealed however that [ 18 F]FDR 3 does not accumulate in the tumour as efficiently as [ 18 F]FDG over longer time periods. Conclusions: [ 18 F]FDR 3 can be rapidly synthesised in a two enzyme protocol and used to image tumours in small animal models

Tratamento da síndrome parkinsoniana pelo L-dopa Parkinsonism's treatment by L-Dopa

Directory of Open Access Journals (Sweden)

Roberto Melaragno

1971-12-01

Full Text Available O trabalho refere o tratamento com L-Dopa de 33 pacientes internados, sendo 19 homens e 14 mulheres. Os casos foram agrupados, segundo uma classificação esquemática, em leves, moderados, intensos e severos. As idades dos pacientes, previamente operados ou não, variaram de 42 a 78 anos. O esquema de medicação constou de administração de L-Dopa na dose inicial de 500 mg associado a um inibidor da MAO. A dose de L-Dopa era elevada de 500 mg cada 3 ou 4 dias, segundo a tolerância de cada paciente. Todos os sintomas dependentes, direta ou indiretamente, da rigidez tiveram melhoras mais nítidas em relação aos tremores. Durante a administração do medicamento os teores sangüíneos de ácido úrico e uréia, mostraram tendência para se elevar; a reserva alcalina, pelo contrário, tendeu para a diminuição; o hemograma revelou muitas vezes eosinofilia por vezes intensa. Os efeitos colaterais foram catalogados em dois tipos — efeitos adrenérgicos e efeitos dopaminérgicos — correspondentes a duas fases: uma primeira, de pequena duração, na qual foram usados concomitantemente o L-Dopa e um inibidor da MAO, surgindo cefaléia hipertensão arterial paroxística, rubor facial, sudorese, tenesmo vesical e angina pectoris; numa segunda fase surgiram os efeitos colaterais ditos dopaminérgicos, proporcionais à gravidade clínica do caso, cujas manifestações principais foram hipotensão arterial, sudorese fria, arritmia cardíaca e lipotimia. As complicações clínicas gerais eram representados habitualmente por anorexia, obstipação intestinal, náuseas, vômitos, discretas alterações do estado psíquico com depressão e euforia. Dentre as complicações neurológicas foram assinalados o estado parkinsonóide, discinesias e acatisia.The results of the treatment with L-Dopa of 33 patients (19 males and 14 females are reported. The cases were separated, acording to their symptoms and signs, in slight, moderate, intense and severe ones

High performance microbiological transformation of L-tyrosine to L-dopa by Yarrowia lipolytica NRRL-143

Directory of Open Access Journals (Sweden)

Shultz Jeffry L

2007-08-01

Full Text Available Abstract Background The 3,4-dihydroxy phenyl L-alanine (L-dopa is a drug of choice for Parkinson's disease, controlling changes in energy metabolism enzymes of the myocardium following neurogenic injury. Aspergillus oryzae is commonly used for L-dopa production; however, potential improvements in ease of handling, growth rate and environmental impact have led to an interest in exploiting alternative yeasts. The two important elements required for L-dopa production are intracellular tyrosinases (thus pre-grown yeast cells are required for the transformation of L-tyrosine to L-dopa and L-ascorbate, which acts as a reducing agent. Results Pre-grown cells of Yarrowia lipolytica NRRL-143 were used for the microbiological transformation of L-tyrosine to L-dopa. Different diatomite concentrations (0.5–3.0 mg/ml were added to the acidic (pH 3.5 reaction mixture. Maximum L-dopa biosynthesis (2.96 mg/ml L-dopa from 2.68 mg/ml L-tyrosine was obtained when 2.0 mg/ml diatomite was added 15 min after the start of the reaction. After optimizing reaction time (30 min, and yeast cell concentration (2.5 mg/ml, an overall 12.5 fold higher L-dopa production rate was observed when compared to the control. Significant enhancements in Yp/s, Qs and qs over the control were observed. Conclusion Diatomite (2.0 mg/ml addition 15 min after reaction commencement improved microbiological transformation of L-tyrosine to L-dopa (3.48 mg/ml; p ≤ 0.05 by Y. lipolytica NRRL-143. A 35% higher substrate conversion rate was achieved when compared to the control.

Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA

Directory of Open Access Journals (Sweden)

Stephanie C. Gantz

2015-08-01

Full Text Available Imbalance between the dopamine and serotonin (5-HT neurotransmitter systems has been implicated in the comorbidity of Parkinson’s disease (PD and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices. Application of L-DOPA augmented the D2-receptor-mediated inhibitory postsynaptic current (IPSC in dopamine neurons of the substantia nigra. This augmentation was largely due to dopamine release from 5-HT terminals. Selective optogenetic stimulation of 5-HT terminals evoked dopamine release, producing D2-receptor-mediated IPSCs following treatment with L-DOPA. In the dorsal raphe, L-DOPA produced a long-lasting depression of the 5-HT1A-receptor-mediated IPSC in 5-HT neurons. When D2 receptors were expressed in the dorsal raphe, application of L-DOPA resulted in a D2-receptor-mediated IPSC. Thus, treatment with L-DOPA caused ectopic dopamine release from 5-HT terminals and a loss of 5-HT-mediated synaptic transmission.

Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

Directory of Open Access Journals (Sweden)

Veronica Ghiglieri

2012-01-01

Full Text Available In Parkinson’s disease (PD, alteration of dopamine- (DA- dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID. Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia.

Science.gov (United States)

Havelund, Jesper F; Andersen, Andreas D; Binzer, Michael; Blaabjerg, Morten; Heegaard, Niels H H; Stenager, Egon; Faergeman, Nils J; Gramsbergen, Jan Bert

2017-09-01

L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study, we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n = 26) were clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 h after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid of controls (n = 14), Parkinson patients receiving no L-DOPA (n = 8), patients treated with L-DOPA without dyskinesia (n = 8), and patients with L-DOPA-induced dyskinesia (n = 10) using liquid chromatography-mass spectrometry. We observed approximately fourfold increase in the 3-hydroxykynurenine/kynurenic acid ratio in plasma of Parkinson's patients with L-DOPA-induced dyskinesia. Anthranilic acid levels were decreased in plasma and cerebrospinal fluid of this patient group. 5-Hydroxytryptophan levels were twofold increased in all L-DOPA-treated Parkinson's patients. We conclude that a higher 3-hydroxykynurenine/kynurenic acid ratio in plasma may serve as a biomarker for L-DOPA-induced dyskinesia. Longitudinal studies including larger patients cohorts are needed to verify whether the changes observed here may serve as a prognostic marker for L-DOPA-induced dyskinesia. © 2017 International Society for Neurochemistry.

The role of L-DOPA in plants

Science.gov (United States)

Soares, Anderson Ricardo; Marchiosi, Rogério; Siqueira-Soares, Rita de Cássia; Barbosa de Lima, Rogério; Dantas dos Santos, Wanderley; Ferrarese-Filho, Osvaldo

2014-01-01

Since higher plants regularly release organic compounds into the environment, their decay products are often added to the soil matrix and a few have been reported as agents of plant-plant interactions. These compounds, active against higher plants, typically suppress seed germination, cause injury to root growth and other meristems, and inhibit seedling growth. Mucuna pruriens is an example of a successful cover crop with several highly active secondary chemical agents that are produced by its seeds, leaves and roots. The main phytotoxic compound encountered is the non-protein amino acid L-3,4-dihydroxyphenylalanine (L-DOPA), which is used in treating the symptoms of Parkinson disease. In plants, L-DOPA is a precursor of many alkaloids, catecholamines, and melanin and is released from Mucuna into soils, inhibiting the growth of nearby plant species. This review summarizes knowledge regarding L-DOPA in plants, providing a brief overview about its metabolic actions. PMID:24598311

[Scans without Evidence of Dopamine Deficit (SWEDDs)].

Science.gov (United States)

Mukai, Yohei; Murata, Miho

2016-01-01

Dopamine transporter (DaT) single-photon emission computed tomography (SPECT) and [18F]fluoro-L-DOPA ([18F]DOPA) positron emission tomography (PET) facilitate the investigation of dopaminergic hypofunction in neurodegenerative diseases. DaT SPECT and [18F]DOPA PET have been adopted as survey tools in clinical trials. In a large study on Parkinson's disease, 4-15% of subjects clinically diagnosed with early-stage Parkinson's disease had normal dopaminergic functional imaging scans. These are called Scans without Evidence of Dopamine Deficit (SWEDDs), and are considered to represent a state different from Parkinson's disease. Neurological diseases that exhibit parkinsonism and have normal dopaminergic cells in the nigrostriatal system (e.g., essential tremor, psychogenic parkinsonism, DOPA-responsive dystonia, vascular parkinsonism, drug-induced parkinsonism, manganism, brain tumor, myoclonus-dystonia (DYT11), and fragile X syndrome) might be diagnosed with SWEDDs. True bradykinesia with fatigue or decrement may be useful for distinguishing between Parkinson's disease and SWEDDs. However, because SWEDDs encompass many diseases, their properties may not be uniform. In this review, we discuss DaT SPECT, the concept of SWEDDs, and differential diagnosis.

Quantification of [18F]FDOPA and [18F]-3-OMFD in pig serum - a new TLC method in comparison with HPLC

International Nuclear Information System (INIS)

Pawelke, B.; Fuechtner, F.; Bergmann, R.; Brust, P.

2002-01-01

A novel TLC method for convenient quantification of [ 18 F]FDOPA and [ 18 F]-3-OMFD in routine operation was developed and the results assessed in comparison with an HPLC analysis. The two methods were found to correlate well. [ 18 F]fluoride which resisted determination on HPLC RP-18 columns was also quantified by TLC. (orig.)

Pupillometry as an indicator of L-DOPA dosages in Parkinson's disease patients.

Science.gov (United States)

Bartošová, O; Bonnet, C; Ulmanová, O; Šíma, M; Perlík, F; Růžička, E; Slanař, O

2018-04-01

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R 2  = 0.78) and the total daily L-DOPA dose (R 2  = 0.93). A sigmoid-shaped curve best describes the dose-response relationship, with a ceiling effect at about 400 mg L-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of L-DOPA, especially with daily doses below 400 mg L-DOPA.

Loss of metabolites from monkey striatum during PET with FDOPA

DEFF Research Database (Denmark)

Cumming, P; Munk, O L; Doudet, D

2001-01-01

diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

Enhanced production of L-DOPA in cell cultures of Mucuna pruriens L. and Mucuna prurita H.

Science.gov (United States)

Raghavendra, S; Kumar, V; Ramesh, C K; Khan, M H Moinuddin

2012-01-01

A comparative study on the production of 3,4-dihydroxyphenylalanine (L-DOPA) was carried out in cell cultures of two Mucuna species by elicitor treatment and precursor feeding. The influence of elicitors and the precursor molecule on L-DOPA production, polyphenol oxidase (PPO) and tyrosinase activities was also studied. Callus cultures were initiated in Mucuna pruriens L. and Mucuna prurita H. on MS medium supplemented with BAP and IAA at different concentrations. Suspension cultures were established in MS liquid medium supplemented with BAP, IAA, the elicitors methyl jasmonate, chitin and pectin or the precursor L-tyrosine at different concentrations for L-DOPA production. Compared to the controls, several-fold increases in L-DOPA concentration were observed in elicitor-treated and precursor-fed suspension cultures of both plant species. L-DOPA concentrations were comparatively higher in precursor-fed cultures than those receiving elicitor treatments. A parallel increase in tyrosinase and PPO levels was also observed. Loss of cell viability was observed at high concentrations of elicitor-treated cultures, whereas L-tyrosine did not cause any cell death. Compared to elicitor treatments, precursor feeding resulted in higher concentrations of L-DOPA production and tyrosinase activity. The efficacy of L-DOPA production was found to be higher for suspension cultures of M. pruriens compared to M. prurita in all treatments.

Contemporary nuclear medicine diagnostics of neuroendocrine tumors

Directory of Open Access Journals (Sweden)

Todorović-Tirnanić Mila

2015-01-01

Full Text Available The new positron emission tomography (PET/CT methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1 somatostatin analogues labeled with indium-111 (111In-pentetreotide or technetium-99m (99mTc-EDDA/HYNIC-TOC; 2 noradrenaline analogue labeled with iodine-131 or -123 (131I/123I-MIBG; or 3 99mTc(V-DMSA. Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor imaging, after intravenous injection of pharmaceuticals labeled with positron emitters [fluorine-18 (18F, galium-68 (68Ga, or carbon-11 (11C]: 1 glucose analogue (18FDG; 2 somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga-DOTANOC; 3 aminoacid precursors of bioamines: [a dopamine precursor 18F-DOPA (6-18F-dihydroxyphenylalanine, b serotonin precursor 11C-5HTP (11C-5-hydroxytryptophan]; or 4 dopamine analogue 18F-DA (6-18F-fluorodopamine. Conventional and contemporary (PET/ CT somatostatin receptor detection showed identical high specificity (92%, but conventional had very low sensitivity (52% compared to PET/CT (97%. It means that almost every second neuroendocrine tumor detected by contemporary method cannot be discovered using conventional (classic method. In metastatic pheochromocytoma detection contemporary (PET/ CT methods (18F-DOPA and 18F-DA have higher sensitivity than conventional (131I/123I-MIBG. In medullary thyroid carcinoma diagnostics contemporary method (18F-DOPA is more sensitive than conventional 99mTc(V-DMSA method, and is similar to 18FDG, computed tomography and magnetic resonance. In carcinoid detection contemporary method (18F-DOPA shows similar results with contemporary somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine tumors it is worse. To conclude, contemporary (PET/CT methods for

Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure.

Directory of Open Access Journals (Sweden)

Birger Scholz

Full Text Available L-3,4-dihydroxypheylalanine (L-dopa-induced dyskinesia represent a debilitating complication of therapy for Parkinson's disease (PD that result from a progressive sensitization through repeated L-dopa exposures. The MPTP macaque model was used to study the proteome in dopamine-depleted striatum with and without subsequent acute and chronic L-dopa treatment using two-dimensional difference in-gel electrophoresis (2D-DIGE and mass spectrometry. The present data suggest that the dopamine-depleted striatum is so sensitive to de novo L-dopa treatment that the first ever administration alone would be able (i to induce rapid post-translational modification-based proteomic changes that are specific to this first exposure and (ii, possibly, lead to irreversible protein level changes that would be not further modified by chronic L-dopa treatment. The apparent equivalence between first and chronic L-dopa administration suggests that priming would be the direct consequence of dopamine loss, the first L-dopa administrations only exacerbating the sensitization process but not inducing it.

A simplified one-pot synthesis of 9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([{sup 18}F]FHPG) and 9-(4-[{sup 18}F]Fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG) for gene therapy

Energy Technology Data Exchange (ETDEWEB)

Shiue, Grace G.; Shiue, Chyng-Yann E-mail: Shiue@rad.upenn.edu; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A

2001-10-01

9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([{sup 18}F]FHPG, 2) has been synthesized by nucleophilic substitution of N{sup 2}-(p-anisyldiphenylmethyl)-9-{l_brace}[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl{r_brace}guanine (1) with potassium [{sup 18}F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126{+-}0.022, n=5 and 0.165{+-}0.023, n=5, respectively). Although it contains non-radioactive ganciclovir ({approx}5-30 {mu}g) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains {approx}10-25 {mu}g of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in

Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia

DEFF Research Database (Denmark)

Havelund, Jesper F; Dammann Andersen, Andreas; Binzer, Michael

2017-01-01

L-DOPA is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered...... levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n=26) were...... clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 hours after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid...

Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA

OpenAIRE

Gantz, Stephanie C.; Levitt, Erica S.; Llamosas Muñozguren, Nerea; Neve, Kim A.; Williams, John T.

2015-01-01

Imbalance between the dopamine and serotonin (5-HT) neurotransmitter systems has been implicated in the comorbidity of Parkinson's disease (PD) and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices. Application of L-DOPA augmented the D2-receptor-mediated inhibitory postsynaptic current (IPSC) in dopamine neurons of the substantia nigr...

Guideline for PET/CT imaging of neuroendocrine neoplasms withGa-DOTA-conjugated somatostatin receptor targeting peptides andF-DOPA

DEFF Research Database (Denmark)

Bozkurt, Murat Fani; Virgolini, Irene; Balogova, Sona

2017-01-01

PURPOSE & METHODS: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing......, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using68Ga-DOTA-conjugated peptides, as well as18F-DOPA imaging for various neuroendocrine neoplasms. RESULTS & CONCLUSION: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with68Ga...

A simplified one-pot synthesis of 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy

International Nuclear Information System (INIS)

Shiue, Grace G.; Shiue, Chyng-Yann; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A.

2001-01-01

9-[(3-[ 18 F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG, 2) has been synthesized by nucleophilic substitution of N 2 -(p-anisyldiphenylmethyl)-9-{[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl}guanine (1) with potassium [ 18 F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[ 18 F]fluoro-3-hydroxymethylbutyl)guanine ([ 18 F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126±0.022, n=5 and 0.165±0.023, n=5, respectively). Although it contains non-radioactive ganciclovir (∼5-30 μg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains ∼10-25 μg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is

Betalain production is possible in anthocyanin-producing plant species given the presence of DOPA-dioxygenase and L-DOPA.

Science.gov (United States)

Harris, Nilangani N; Javellana, John; Davies, Kevin M; Lewis, David H; Jameson, Paula E; Deroles, Simon C; Calcott, Kate E; Gould, Kevin S; Schwinn, Kathy E

2012-03-12

Carotenoids and anthocyanins are the predominant non-chlorophyll pigments in plants. However, certain families within the order Caryophyllales produce another class of pigments, the betalains, instead of anthocyanins. The occurrence of betalains and anthocyanins is mutually exclusive. Betalains are divided into two classes, the betaxanthins and betacyanins, which produce yellow to orange or violet colours, respectively. In this article we show betalain production in species that normally produce anthocyanins, through a combination of genetic modification and substrate feeding. The biolistic introduction of DNA constructs for transient overexpression of two different dihydroxyphenylalanine (DOPA) dioxygenases (DODs), and feeding of DOD substrate (L-DOPA), was sufficient to induce betalain production in cell cultures of Solanum tuberosum (potato) and petals of Antirrhinum majus. HPLC analysis showed both betaxanthins and betacyanins were produced. Multi-cell foci with yellow, orange and/or red colours occurred, with either a fungal DOD (from Amanita muscaria) or a plant DOD (from Portulaca grandiflora), and the yellow/orange foci showed green autofluorescence characteristic of betaxanthins. Stably transformed Arabidopsis thaliana (arabidopsis) lines containing 35S: AmDOD produced yellow colouration in flowers and orange-red colouration in seedlings when fed L-DOPA. These tissues also showed green autofluorescence. HPLC analysis of the transgenic seedlings fed L-DOPA confirmed betaxanthin production. The fact that the introduction of DOD along with a supply of its substrate (L-DOPA) was sufficient to induce betacyanin production reveals the presence of a background enzyme, possibly a tyrosinase, that can convert L-DOPA to cyclo-DOPA (or dopaxanthin to betacyanin) in at least some anthocyanin-producing plants. The plants also demonstrate that betalains can accumulate in anthocyanin-producing species. Thus, introduction of a DOD and an enzyme capable of converting

Betalain production is possible in anthocyanin-producing plant species given the presence of DOPA-dioxygenase and L-DOPA

Directory of Open Access Journals (Sweden)

Harris Nilangani N

2012-03-01

Full Text Available Abstract Background Carotenoids and anthocyanins are the predominant non-chlorophyll pigments in plants. However, certain families within the order Caryophyllales produce another class of pigments, the betalains, instead of anthocyanins. The occurrence of betalains and anthocyanins is mutually exclusive. Betalains are divided into two classes, the betaxanthins and betacyanins, which produce yellow to orange or violet colours, respectively. In this article we show betalain production in species that normally produce anthocyanins, through a combination of genetic modification and substrate feeding. Results The biolistic introduction of DNA constructs for transient overexpression of two different dihydroxyphenylalanine (DOPA dioxygenases (DODs, and feeding of DOD substrate (L-DOPA, was sufficient to induce betalain production in cell cultures of Solanum tuberosum (potato and petals of Antirrhinum majus. HPLC analysis showed both betaxanthins and betacyanins were produced. Multi-cell foci with yellow, orange and/or red colours occurred, with either a fungal DOD (from Amanita muscaria or a plant DOD (from Portulaca grandiflora, and the yellow/orange foci showed green autofluorescence characteristic of betaxanthins. Stably transformed Arabidopsis thaliana (arabidopsis lines containing 35S: AmDOD produced yellow colouration in flowers and orange-red colouration in seedlings when fed L-DOPA. These tissues also showed green autofluorescence. HPLC analysis of the transgenic seedlings fed L-DOPA confirmed betaxanthin production. Conclusions The fact that the introduction of DOD along with a supply of its substrate (L-DOPA was sufficient to induce betacyanin production reveals the presence of a background enzyme, possibly a tyrosinase, that can convert L-DOPA to cyclo-DOPA (or dopaxanthin to betacyanin in at least some anthocyanin-producing plants. The plants also demonstrate that betalains can accumulate in anthocyanin-producing species. Thus, introduction

Factors affecting ¹⁸F FDOPA standardized uptake value in patients with primary brain tumors after treatment.

Science.gov (United States)

Chiaravalloti, Agostino; Fiorentini, Alessandro; Villani, Veronica; Carapella, Carmine; Pace, Andrea; Di Pietro, Barbara; Di Russo, Carmen; Palumbo, Barbara; Floris, Roberto; Schillaci, Orazio

2015-04-01

To investigate the factors affecting (18)F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent (18)F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (±42.27), 16.04 (±29.08) and 28.62 (±34.49) months respectively. (18)F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect (18)F FDOPA uptake. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of 18FDG, 18FDOPA PET/CT and 99mTc bone scintigraphy imaging in Erdheim–Chester disease

Energy Technology Data Exchange (ETDEWEB)

García-Gómez, F.J., E-mail: javier191185@gmail.com [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Acevedo-Báñez, I.; Martínez-Castillo, R.; Tirado-Hospital, J.L.; Cuenca-Cuenca, J.I.; Pachón-Garrudo, V.M.; Álvarez-Pérez, R.M.; García-Jiménez, R. [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Rivas-Infante, E. [Department of Pathology, Virgen del Rocío Universitary Hospital, Seville (Spain); García-Morillo, J.S. [Department of Internal Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Borrego-Dorado, I. [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain)

2015-08-15

Highlights: • Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. • Multifocal nature of involvement in ECD can produce a wide variety of clinical signs. In our experience, neurological involvement is associated with mortality in all cases. Characteristic long bone osteosclerosis was a quasi-pathognomonic finding in bone scintigraphy. • To the best of our knowledge, the 18FDOPA-PET/CT not seem useful in the initial staging of ECD based on a single case report. • Bone scintigraphy and the 18FDG-PET/CT that were particularly useful in despite systemic involvement, locate the optimum site for biopsy and treatment response evaluation. In this context, a baseline 18FDG-PET/CT with an optional bone scintigraphy may help in monitoring the disease and could be considered when patients were incidentally diagnosed and periodically follow-up 18FDG-PET/CT must be performed in the follow up to evaluate the treatment response. - Abstract: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes that stain positively for CD68 marker but not express CD1a and S100 proteins. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. Multisystemic involvement leads to a wide variety of clinical manifestations that results in a poor prognosis although recent advances in treatment. We present the clinical, nuclear medicine findings and therapeutic aspects of a serie of 6 patients with histopathological diagnosis of ECD, who have undergone both bone scintigraphy (BS) and 18F-fluorodeoxyglucose (18FDG)-PET/CT scans in our institution. A complementary 18F-fluorodopa (18FDOPA)-PET/CT was performed in one case. Three different

The role of 18FDG, 18FDOPA PET/CT and 99mTc bone scintigraphy imaging in Erdheim–Chester disease

International Nuclear Information System (INIS)

García-Gómez, F.J.; Acevedo-Báñez, I.; Martínez-Castillo, R.; Tirado-Hospital, J.L.; Cuenca-Cuenca, J.I.; Pachón-Garrudo, V.M.; Álvarez-Pérez, R.M.; García-Jiménez, R.; Rivas-Infante, E.; García-Morillo, J.S.; Borrego-Dorado, I.

2015-01-01

Highlights: • Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. • Multifocal nature of involvement in ECD can produce a wide variety of clinical signs. In our experience, neurological involvement is associated with mortality in all cases. Characteristic long bone osteosclerosis was a quasi-pathognomonic finding in bone scintigraphy. • To the best of our knowledge, the 18FDOPA-PET/CT not seem useful in the initial staging of ECD based on a single case report. • Bone scintigraphy and the 18FDG-PET/CT that were particularly useful in despite systemic involvement, locate the optimum site for biopsy and treatment response evaluation. In this context, a baseline 18FDG-PET/CT with an optional bone scintigraphy may help in monitoring the disease and could be considered when patients were incidentally diagnosed and periodically follow-up 18FDG-PET/CT must be performed in the follow up to evaluate the treatment response. - Abstract: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes that stain positively for CD68 marker but not express CD1a and S100 proteins. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. Multisystemic involvement leads to a wide variety of clinical manifestations that results in a poor prognosis although recent advances in treatment. We present the clinical, nuclear medicine findings and therapeutic aspects of a serie of 6 patients with histopathological diagnosis of ECD, who have undergone both bone scintigraphy (BS) and 18F-fluorodeoxyglucose (18FDG)-PET/CT scans in our institution. A complementary 18F-fluorodopa (18FDOPA)-PET/CT was performed in one case. Three different

Stability study of 2-[18F]Fluoro-2-Deoxy-D-Glucose (18FDG) stored at room temperature by physicochemical and microbiological assays

International Nuclear Information System (INIS)

Ferreira, Soraya Z.; Silva, Juliana B. da; Waquil, Samira S.; Correia, Ricardo F.

2009-01-01

The most widely used radiopharmaceutical in the expanding medical imaging technology of Positron Emission Tomography (PET) is 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 FDG). The increasing demand for 18 FDG requires reliable production in large amounts. The synthesis of 18 FDG is based on a nucleophilic substitution of the triflate-leaving group from the precursor, mannose triflate, in the presence of Crypt and 2.2.2, as a phase-transfer agent. After labeling, the removal of the acetyl protecting groups from resulting 2-[ 18 F]fluoro-1,3,4,6-tetra-Oacetyl- D-glucose is performed by alkaline hydrolysis, followed by purification and final filtration (0.22 μm). It was reported that 18 FDG decomposes in vitro, resulting in the degradation of the radiochemical purity with time. The aim of this study was to evaluate physicochemical and microbiological stability of 18 FDG, stored at room temperature (15-30 deg C), at different time intervals. It was investigated how the quality of this radiopharmaceutical varies with time under the influence of environmental factors. 18 FDG pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins and sterility were evaluated according to the United States Pharmacopeia 31 th edition analytical methods and acceptance criteria. The results suggest that 18 FDG has physicochemical and microbiological stability up to 10 hours after the end of synthesis, under experimental conditions. (author)

Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine

International Nuclear Information System (INIS)

Becherer, Alexander; Karanikas, Georgios; Szabo, Monica; Zettinig, Georg; Wadsak, Wolfgang; Kletter, Kurt; Asenbaum, Susanne; Marosi, Christine; Henk, Christine; Wunderbaldinger, Patrick; Czech, Thomas

2003-01-01

Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[ 18 F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean±SD), were 2.05±0.91 for MET and 2.04±0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of 18 F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging. (orig.)

Inducing mutations through γ-irradiation in seeds of Mucuna pruriens for developing high L-DOPA-yielding genotypes.

Science.gov (United States)

Singh, Susheel Kumar; Yadav, Deepti; Lal, Raj Kishori; Gupta, Madan M; Dhawan, Sunita Singh

2017-04-01

To develop elite genotypes in Mucuna pruriens (L.) DC with high L-DOPA (L-3, 4 dihydroxyphenylalanine) yields, with non-itching characteristics and better adaptability by applying γ-irradiation. Molecular and chemical analysis was performed for screening based on specific characteristics desired for developing suitable genotypes. Developed, mutant populations were analyzed for L-DOPA % in seeds through TLC (thin layer chromatography), and the results obtained were validated with the HPLC (High performance liquid chromatography). The DNA (Deoxyribonucleic acid) was isolated from the leaf at the initial stage and used for DNA polymorphism. RNA (Ribonucleic acid) was isolated from the leaf during maturity and used for expression analysis. The selected mutant T-I-7 showed 5.7% L-DOPA content compared to 3.18% of parent CIM-Ajar. The total polymorphism obtained was 57% with the molecular marker analysis. The gene expression analysis showed higher fold change expression of the dopadecarboxylase gene (DDC) in control compared to selected mutants (T-I-7, T-II-23, T-IV-9, T-VI-1). DNA polymorphism was used for the screening of mutants for efficient screening at an early stage. TLC was found suitable for the large-scale comparative chemical analysis of L-DOPA. The expression profile of DDC clearly demonstrated the higher yields of L-DOPA in selected mutants developed by γ-irradiation in the seeds of the control.

Impairment of Serotonergic Transmission by the Antiparkinsonian Drug L-DOPA: Mechanisms and Clinical Implications

Directory of Open Access Journals (Sweden)

Cristina Miguelez

2017-09-01

Full Text Available The link between the anti-Parkinsonian drug L-3,4-dihydroxyphenylalanine (L-DOPA and the serotonergic (5-HT system has been long established and has received increased attention during the last decade. Most studies have focused on the fact that L-DOPA can be transformed into dopamine (DA and released from 5-HT terminals, which is especially important for the management of L-DOPA-induced dyskinesia. In patients, treatment using L-DOPA also impacts 5-HT neurotransmission; however, few studies have investigated the mechanisms of this effect. The purpose of this review is to summarize the electrophysiological and neurochemical data concerning the effects of L-DOPA on 5-HT cell function. This review will argue that L-DOPA disrupts the link between the electrical activity of 5-HT neurons and 5-HT release as well as that between 5-HT release and extracellular 5-HT levels. These effects are caused by the actions of L-DOPA and DA in 5-HT neurons, which affect 5-HT neurotransmission from the biosynthesis of 5-HT to the impairment of the 5-HT transporter. The interaction between L-DOPA and 5-HT transmission is especially relevant in those Parkinson’s disease (PD patients that suffer dyskinesia, comorbid anxiety or depression, since the efficacy of antidepressants or 5-HT compounds may be affected.

Application of 18F-FDOPA PET imaging in gliomas%18F-FDOPA PET显像在脑胶质瘤中的临床应用价值

Institute of Scientific and Technical Information of China (English)

葛璟洁; 张政伟; 陆秀宏(综述); 管一晖(审校)

2016-01-01

脑胶质瘤是发病率最高的神经系统来源肿瘤。目前临床上诊断胶质瘤的方法主要为MRI平扫及增强，但存在一定的局限性。近年来，随着PET与核素显像剂的不断发展和改进，其在胶质瘤领域的研究越来越深入，尤其是18F-FDOPA PET显像在原发性及复发性胶质瘤的诊断、鉴别、分级、定位、治疗和预后评估中具有较高的临床应用价值。本文就此进行综述。%Glioma is one of the most common neurologically originated tumor. Although MRI scanning is the major approach to make diagnosis of glioma at present, it still has some limitations. With the development and improvement of positron emission tomography imaging techniques and radionuclide agents, PET imaging such as 18F-FDOPA PET imaging has played a more and more important role in the diagnosis, discrimination, grading, localization and prognosis evaluation of primary and recurrent gliomas. The present paper summarizes the research progress in this ifeld.

Brain tumour imaging with PET: a comparison between [{sup 18}F]fluorodopa and [{sup 11}C]methionine

Energy Technology Data Exchange (ETDEWEB)

Becherer, Alexander; Karanikas, Georgios; Szabo, Monica; Zettinig, Georg; Wadsak, Wolfgang; Kletter, Kurt [Department of Nuclear Medicine, Medical School, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Asenbaum, Susanne [Department of Neurology, Medical School, University of Vienna, Vienna (Austria); Marosi, Christine [Department of Oncology, Medical School, University of Vienna, Vienna (Austria); Henk, Christine; Wunderbaldinger, Patrick [Department of Radiology, Medical School, University of Vienna, Vienna (Austria); Czech, Thomas [Department of Neurosurgery, Medical School, University of Vienna, Vienna (Austria)

2003-11-01

Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[{sup 18}F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean{+-}SD), were 2.05{+-}0.91 for MET and 2.04{+-}0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of {sup 18}F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging. (orig.)

LC-MSdetermination of L-DOPA concentration in the leaf and flower tissues of six faba bean (Vicia fabaL. lines with common and rare flowercolors

Directory of Open Access Journals (Sweden)

Jinguo Hu

2015-07-01

Full Text Available Background: Parkinson’s disease (PD is the second most common neurodegenerative disorder characterized by the loss of muscle control, which causes trembling of the limbs and head as well as impaired balance. L-DOPA (L-3,4-dihydroxy phenylalanine is the major ingredient of several prescription drugs used to treat PD. Faba bean (Vicia faba L. is one of the few plant species that is known to produce L-DOPA and has the potential to be developed as a functional food crop for people suffering with PD. Objective: Aimed to provide needed information for people who want to use faba bean as a natural remedy or functional food to relieve PD symptoms, this study analyzed the variation of L-DOPA concentration in the leaf and flower tissues of six faba bean lines with common and rare flower colors. Methods: Leaf and flower samples were taken from field grown plants with different flower colors, namely, pink with purple lines and black dots, pure white, brown, and crimson. Samples were freeze-dried and L-DOPA was quantified by a LC-MS system consisting of an ACQUITY UPLC in line with a Synapt G2 HDMS quadrupole time-of-flight mass spectrometer. This experiment was carried out in two consecutive years (2012 and 2013 and the plants used in the second year were grown from the seeds harvested from the plants used in the first year. Results and Discussion: Our two-year study revealed a high level of variation in L-DOPA concentration for leaf and flower tissues among the six faba bean lines studied. The average L-DOPA concentration based on dry weight (DW in flowers ranged from 27.8 to 63.5 mg/g and 18.2 to 48.7 mg/g for leaf tissues. There was no significant correlation between L-DOPA concentrations in flowers and leaves. The L-DOPA concentration in flowers and in leaves of the same line varied but were not statistically significant between the two years. Ideally, the genotype with the highest average L-DOPA concentration in both flowers and leaves would be grown

The role of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography in the management of patients with carcinoma of unknown primary.

Science.gov (United States)

Deonarine, P; Han, S; Poon, F W; de Wet, C

2013-08-01

Carcinoma of unknown primary is one of the ten most frequent cancers worldwide. Its median survival time is less than 10 months. Detecting primary tumour locations and/or occult metastatic lesions may inform definitive treatment and improve patients' prognosis. We aimed to determine: (1) the sensitivity, specificity and accuracy of (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography; (2) its detection rate of primary tumour locations and occult metastases and (3) factors associated with improved survival times. We retrospectively reviewed all cases in the West of Scotland for the period 1 December 2007 to 31 May 2011 that met all our selection criteria: (1) diagnosis of carcinoma of unknown primary; (2) a thorough but negative 'work-up' and (3) (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography report. Statistical methods included frequencies, Kaplan-Meier graphs and log-rank tests to compare survival times. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected primary tumour sites in 19/51 (37.3%) and occult metastases in 28/51 (54.9%) of eligible patients. Its sensitivity, specificity and accuracy were 79.2%, 70.4% and 74.5%, respectively; 20/51 (39.2%) patients died during the study period with a median survival of 8.4 months (range 21.4, SD ± 6.2). The number of metastatic locations was strongly associated with survival (p = 0.002), but detection of a primary tumour site (p = 0.174) or histopathology (p = 0.301) was not. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected occult metastatic sites in the majority and a primary cancer location in a substantial minority of patients. Our results were comparable with international literature and may indicate that (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography have an early role to improve the accuracy of cancer staging and to optimise carcinoma of unknown

Renal hemodynamic response to L-dopa during acute renal failure in man

Energy Technology Data Exchange (ETDEWEB)

Zech, P; Collard, M; Guey, A; Plantier, J; Bernard, M; Berthoux, F; Pinet, A; Traeger, J [Hopital Edouard-Herriot, 69 - Lyon (France)

1975-12-20

Twelve patients with acute renal failure underwent L-dopa infusion into a renal artery and /sup 133/Xenon wash-out recordings before and during the infusion. Urine volume and sodium output were also compared during two 24 hours periods, before and after the procedure. Hemodynamic data were compared with data obtained from a matched group of patients receiving Furosemide (8 patients) in place of L-dopa. Only L-dopa infusion significantly increased outer cortical distribution. No blood flow change could be demonstrated in any component nor did the drug improve unitary excretion or the general course of the disease. Control data shows that reduced cortical distribution is the most consistent feature of acute renal failure, so that L-dopa does partially improve intrarenal hemodynamics in this condition. The failure of the drug to restore kidney function may be explained by the following reasons: inability of the agent to restore a normal wash-out pattern: involvment of non-hemodynamic factors, as suggested by comparing similar wash-out improvements after L-dopa in acute glomerulonephritis and in reversible acute renal failure.

Renal hemodynamic response to L-dopa during acute renal failure in man

International Nuclear Information System (INIS)

Zech, P.; Collard, M.; Guey, A.; Plantier, J.; Bernard, M.; Berthoux, F.; Pinet, A.; Traeger, J.

1975-01-01

Twelve patients with acute renal failure underwent L.dopa infusion into a renal artery and 133 Xenon wash-out recordings before and during the infusion. Urine volume and sodium output were also compared during two 24 hours periods, before and after the procedure. Hemodynamic data were compared with data obtained from a matched group of patients receiving Furosemide (8 patients) in place of L.dopa. Only L.dopa infusion significantly increased outer cortical distribution. No blood flow change could be demonstrated in any component nor did the drug improve unitary excretion or the general course of the disease. Control data shows that reduced cortical distribution is the most consistent feature of acute renal failure, so that L.dopa does partially improve intrarenal hemodynamics in this condition. The failure of the drug to restore kidney function may be explained by the following reasons: inability of the agent to restore a normal wash-out pattern: involvment of non-hemodynamic factors, as suggested by comparing similar wash-out improvements after L.dopa in acute glomerulonephritis and in reversible acute renal failure [fr

Mutation of Aspergillus oryzae for improved production of 3, 4-dihydroxy phenyl-L-alanine (L-DOPA from L-tyrosine Mutação de Aspergillus orizae para produção melhorada de 3,4-dihidroxi fenil-L-alanina (L-DOPA a partir de L-tirosina

Directory of Open Access Journals (Sweden)

Ikram-ul Haq

2006-03-01

Full Text Available Aspergillus oryzae mutant strain UV-7 was further improved for the production of L-DOPA from L-tyrosine using chemical mutation. Different putative mutant strains of organism were tested for the production of L-DOPA in submerged fermentation. Among these putative mutant strains, mutant designated SI-12 gave maximum production of L-DOPA (300 mg L-DOPA.g-1 cells. The production of L-DOPA from different carbon source solutions (So= 30 g.l-1 by mutant culture was investigated at different nitrogen sources, initial pH and temperature values. At optimum pH (pHo= 5.0, and temperature (t=30ºC, 100% sugars were utilized for production and cell mass formation, corresponding to final L-DOPA product yield of 150 mg.g-1 substrate utilized, and maximum volumetric and specific productivities of 125 mg.l-1.h-1, and 150 mg.g-1 cells. h-1, respectively. There was up to 3-fold enhancement in product formation rate. This enhancement is the highest reported in literature. To explain the kinetic mechanism of L-DOPA formation and thermal inactivation of tyrosinase, the thermodynamic parameters were determined with the application of Arrhenius model: activation enthalpy and entropy for product formation, in case of mutant derivative, were 40 k j/mol and 0.076 k j/mol. K for L-DOPA production and 116 k j/mol and 0.590 k j/mol. K for thermal inactivation, respectively. The respective values for product formation were lower while those for product deactivation were higher than the respective values for the parental culture. Therefore, the mutant strain was thermodynamically more resistant to thermal denaturation.A produção de L-DOPA a partir de tirosina pela cepa mutante de Aspergillus orizae UV-7 foi melhorada através de mutação química. Diferentes cepas foram testadas quanto a produção de L-DOPA por fermentação submersa, observando-se que a cepa denominada SI-12 foi a melhor produtora (300 mg de L-DOPA por g de células. A produção de L-DOPA pela cepa

A selective phosphodiesterase 10A inhibitor reduces l-dopa-induced dyskinesias in parkinsonian monkeys.

Science.gov (United States)

Beck, Goichi; Maehara, Shunsuke; Chang, Phat Ly; Papa, Stella M

2018-03-06

Phosphodiesterase 10A is a member of the phosphodiesterase family whose brain expression is restricted to the striatum. Phosphodiesterase 10A regulates cyclic adenosine monophosphate and cyclic guanosine monophosphate, which mediate responses to dopamine receptor activation, and the levels of these cyclic nucleotides are decreased in experimental models of l-dopa-induced dyskinesia. The elevation of cyclic adenosine monophosphate/cyclic guanosine monophosphate levels by phosphodiesterase 10A inhibition may thus be targeted to reduce l-dopa-induced dyskinesia. The present study was aimed at determining the potential antidyskinetic effects of phosphodiesterase 10A inhibitors in a primate model of Parkinson's disease (PD). The experiments performed in this model were also intended to provide translational data for the design of future clinical trials. Five MPTP-treated macaques with advanced parkinsonism and reproducible l-dopa-induced dyskinesia were used. MR1916, a selective phosphodiesterase 10A inhibitor, at doses 0.0015 to 0.05 mg/kg, subcutaneously, or its vehicle (control test) was coadministered with l-dopa methyl ester acutely (predetermined optimal and suboptimal subcutaneous doses) and oral l-dopa chronically as daily treatment for 5 weeks. Standardized scales were used to assess motor disability and l-dopa-induced dyskinesia by blinded examiners. Pharmacokinetics was also examined. MR1916 consistently reduced l-dopa-induced dyskinesia in acute tests of l-dopa optimal and suboptimal doses. Significant effects were present with every MR1916 dose tested, but the most effective was 0.015 mg/kg. None of the MR1916 doses tested affected the antiparkinsonian action of l-dopa at the optimal dose. The anti-l-dopa-induced dyskinesia effect of MR1916 (0.015 mg/kg, subcutaneously) was sustained with chronic administration, indicating that tolerance did not develop over the 5-week treatment. No adverse effects were observed after MR1916 administration acutely or

Statistically optimized biotransformation protocol for continuous production of L-DOPA using Mucuna monosperma callus culture.

Science.gov (United States)

Inamdar, Shrirang Appasaheb; Surwase, Shripad Nagnath; Jadhav, Shekhar Bhagwan; Bapat, Vishwas Anant; Jadhav, Jyoti Prafull

2013-01-01

L-DOPA (3,4-dihydroxyphenyl-L-alanine), a modified amino acid, is an expansively used drug for the Parkinson's disease treatment. In the present study, optimization of nutritional parameters influencing L-DOPA production was attempted using the response surface methodology (RSM) from Mucuna monosperma callus. Optimization of the four factors was carried out using the Box-Behnken design. The optimized levels of factors predicted by the model include tyrosine 0.894 g l(-1), pH 4.99, ascorbic acid 31.62 mg l(-1)and copper sulphate 23.92 mg l(-1), which resulted in highest L-DOPA yield of 0.309 g l(-1). The optimization of medium using RSM resulted in a 3.45-fold increase in the yield of L-DOPA. The ANOVA analysis showed a significant R (2) value (0.9912), model F-value (112.465) and probability (0.0001), with insignificant lack of fit. Optimized medium was used in the laboratory scale column reactor for continuous production of L-DOPA. Uninterrupted flow column exhibited maximum L-DOPA production rate of 200 mg L(-1) h(-1) which is one of the highest values ever reported using plant as a biotransformation source. L-DOPA production was confirmed by HPTLC and HPLC analysis. This study demonstrates the synthesis of L- DOPA using Mucuna monosperma callus using a laboratory scale column reactor.

L-3,4-Dihydroxyphenylalanine (l-DOPA) induces neuroendocrinological, physiological, and immunological regulation in white shrimp, Litopenaeus vannamei.

Science.gov (United States)

Mapanao, Ratchaneegorn; Kuo, Hsin-Wei; Chang, Chin-Chuan; Liu, Kuan-Fu; Cheng, Winton

2018-03-01

L-3,4-Dihydroxyphenylalanine (l-DOPA) is a precursor for dopamine (DA) synthesis. Assessments were conducted to analyze the effects of l-DOPA on mediating regulation of neuroendocrinological, immunological, and physiological parameters in the shrimp, Litopenaeus vannamei when they were individually injected with 0.01 N HCl or l-DOPA at 0.5 or 1.0 μmol shrimp -1 for 60, 120, and 240 min. For catecholamine synthesis evaluation, tyrosine hydroxylase (TH) and DA beta hydroxylase (DBH) activities, l-DOPA, DA, and norepinephrine (NE) levels in hemolymph were determined. The total hemocyte count (THC), differential hemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, phagocytic activity, and clearance efficiency in response to the pathogen, Vibrio alginolyticus were assessed for immune responses, and plasma glucose and lactate levels were for physiological response. Results showed that the TH activity, THC, hyaline cells (HCs), and semigranular cells (SGCs) at 120 min, DA levels at 60-240 min, PO activity in hemocytes per 50 μL of hemolymph at 60-120 min, and PO activity per granulocyte (granular cells (GCs) + SGCs) at 60 min significantly increased, but TH activity, l-DOPA levels, GCs, SGCs, and respiratory bursts in hemocytes per 10 μL of hemolymph at 60 min, respiratory bursts per hemocyte and SOD activity at 120 min, phagocytic activity at 60-240 min, and the clearance efficiency at 60-120 min significantly decreased in shrimp injected with l-DOPA at 1.0 μmol shrimp -1 . In another experiment, 60 min after shrimp had received l-DOPA at 0.5 or 1.0 μmol shrimp -1 , they were challenged with an injection of V. alginolyticus at 2 × 10 5  colony-forming units (cfu) shrimp -1 . The injection of l-DOPA at 1.0 μmol shrimp -1 also significantly increased the cumulative mortality of shrimp by 16.7%, compared to the HCl-challenged control after 120 h. These results suggest

Singlet oxygen generation during the oxidation of L-tyrosine and L-dopa with mushroom tyrosinase

Energy Technology Data Exchange (ETDEWEB)

Miyaji, Akimitsu [Department of Environmental Chemistry and Engineering, Tokyo Institute of Technology, 4259-G1-14, Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Kohno, Masahiro [Department of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-G1-25 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Inoue, Yoshihiro [Showa Pharmaceutical University, 3-3165 Higashi-tamagawagakuen, Machida, Tokyo 194-8543 (Japan); Baba, Toshihide, E-mail: tbaba@chemenv.titech.ac.jp [Department of Environmental Chemistry and Engineering, Tokyo Institute of Technology, 4259-G1-14, Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan)

2016-03-18

The generation of singlet oxygen during the oxidation of tyrosine and L-dopa using mushroom tyrosinase in a phosphate buffer (pH 7.4), the model of melanin synthesis in melanocytes, was examined. The reaction was performed in the presence of 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TEMP), an acceptor of singlet oxygen and the electron spin resonance (ESR) of the spin adduct, 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxy (4-oxo-TEMPO), was measured. An increase in the ESR signal attributable to 4-oxo-TEMPO was observed during the oxidation of tyrosine and L-dopa with tyrosinase, indicating the generation of singlet oxygen. The results suggest that {sup 1}O{sub 2} generation via tyrosinase-catalyzed melanin synthesis occurs in melanocyte. - Highlights: • Generation of singlet oxygen was observed during tyrosinase-catalyzed tyrosine oxidation. • The singlet oxygen generated when tyrosine was converted into dopachrome. • The amount of singlet oxygen is not sufficient for cell toxicity. • It decreased when the hydroxyl radicals and/or superoxide anions were trapped.

Radiosynthesis of [18F]fluorophenyl-L-amino acids by isotopic exchange on carbonyl-activated precursors

International Nuclear Information System (INIS)

Castillo Melean, Johnny

2011-01-01

Aromatic [ 18 F]fluoroamino acids have earlier been developed as promising probes for diagnostics using PET. However, a wider use of these radiofluorinated compounds has been limited due to radiosynthetic constraints. The work here presents an amenable three-step radiosynthesis pathway for the preparation of 2-[ 18 F]fluoro-L-phenylalanine (2-[ 18 F]Fphe), 2-[ 18 F]fluoro-L-tyrosine (2-[ 18 F]Ftyr), 6-[ 18 F]fuoro-L-m-tyrosine (6-[ 18 F]Fmtyr) and 6-[ 18 F]fluoro-L-DOPA (6-[ 18 F]FDOPA). For this, corresponding precursors were 18 F-fluorinated by nucleophilic isotopic exchange, followed by either removal of an activating formyl group with Rh(PPh 3 ) 3 Cl or its conversion by Baeyer-Villiger oxidation, respectively, and subsequent hydrolysis of protecting groups in acidic medium. Two efficient synthetic approaches were developed for the preparation of highly functionalized fluoro-benzaldehydes and -ketones which were used as labeling precursors. The compounds (2S,5S)-tert-butyl 2-tert-butyl-5-(2-fluoro-5-formylbenzyl)-3-methyl-4-oxoimidazolidine-1 -carboxylate (1a), (2S,5S)-tert-butyl 5-(5-acetyl-2-fluorobenzyl)-2-tert-butyl-3-methyl-4-oxoimidazolidine-1 -carboxylate (1c), (2S,5S)-benzyl 2-tert-butyl-5-(2-fluoro-5-formylbenzyl)-3-methyl-4-oxoimidazolidine-1 -carbo-xylate (1d), 4-fluoro-3-(((2S,5R)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl) me-thyl)b enzal-dehyde (1e) and 1-(4-fluoro-3-(((2S,5R)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl) me-thy l)phenyl)ethanone (1f), could be prepared in six steps and overall yields of 41%, 48%, 37%, 27%, and 32%, respectively. (2S,5S)-tert-Butyl 5-(4-(benzyloxy)-2-fluoro-5-formylbenzyl)-2-tert-butyl-3-methyl-4 -oxoimidazolidi ne-1-carboxylate (1b) was prepared in ten steps with an overall yield of 19% while compounds (2S,5S)-tert-butyl 5-(5-(3,5-bis(trifluoromethyl)-benzoyl)-2-fluorobenzyl)-2-tert-butyl-3 -methyl-4-oxoimidazolidine-1-carboxylate (1g) and (2S,5S)-tert-butyl 2-tert-butyl-5-(2-fluoro-5

Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA.

Science.gov (United States)

Zhao, Ting Ting; Kim, Kyung Sook; Shin, Keon Sung; Park, Hyun Jin; Kim, Hyun Jeong; Lee, Kyung Eun; Lee, Myung Koo

2017-09-06

Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant

The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA-Induced Dyskinesia in Parkinsonian Rats.

Science.gov (United States)

Lindenbach, David; Conti, Melissa M; Ostock, Corinne Y; George, Jessica A; Goldenberg, Adam A; Melikhov-Sosin, Mitchell; Nuss, Emily E; Bishop, Christopher

2016-09-21

Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14-16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease

Targeting the D1-N-methyl-D-aspartate receptor complex reduces L-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned Parkinson’s rats

Directory of Open Access Journals (Sweden)

Song L

2016-02-01

Full Text Available Lu Song,1,* Zhanzhao Zhang,2,* Rongguo Hu,1 Jie Cheng,1 Lin Li,1 Qinyi Fan,1 Na Wu,1 Jing Gan,1 Mingzhu Zhou,1 Zhenguo Liu11Department of Neurology, Xinhua Hospital, 2Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: L-3,4-dihydroxyphenylalanine (L-dopa remains the most effective therapy for Parkinson’s disease (PD, but its long-term administration is associated with the development of debilitating motor complications known as L-dopa-induced dyskinesia (LID. Enhanced function of dopamine D1 receptor (D1R and N-methyl-d-aspartate receptor (NMDAR is believed to participate in the pathogenesis of LID. Given the existence of physical and functional interactions between D1R and NMDAR, we explored the effects of uncoupling D1R and NMDA GluN1 (GluN1 interaction on LID by using the Tat-conjugated interfering peptide (Tat-D1-t2. In this study, we demonstrated in 6-hydroxydopamine (6-OHDA-lesioned PD rat model that intrastriatal injection of Tat-D1-t2 alleviated dyskinetic behaviors and downregulated the phosphorylation of DARPP-32 at Thr34 induced by levodopa. Moreover, we also showed intrastriatal administration of Tat-D1-t2 elicited alterations in membranous GluN1 and D1R expression. These findings indicate that D1R/GluN1 complexes may be a molecular target with therapeutic potential for the treatment of dyskinesia in Parkinson’s patients.Keywords: 6-hydroxydopamine, Parkinson’s disease, dyskinesia, L-dopa, D1 receptor, NMDA, protein–protein interaction

1-[18F]fluoro-2-propanol p-toluenesulfonate: a synthon for the preparation of N-([18F]fluoroisopropyl)amines

International Nuclear Information System (INIS)

Groot, T.J. de; Elsinga, P.H.; Visser, G.M.; Vaalburg, W.

1992-01-01

The new radiochemical synthon 1-[ 18 F]fluoro-2-propanol p-toluenesulfonate is prepared with a radiochemical yield of 45% [corrected for decay to beginning of synthesis, synthesis time 40 min]. This compound is used to prepare the [ 18 F]fluoroisopropyl-alkylated derivatives of benzylamine and norephedrine with a yield of 7 and 2% respectively, (synthesis time 90 min). This alkylation reaction a good perspective for the preparation of [ 18 F]fluoro-labelled analogues of β 1 -adrenergic receptor binding ligands for PET. (Author)

Prospective comparison of {sup 68}Ga-DOTATATE and {sup 18}F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

Energy Technology Data Exchange (ETDEWEB)

Archier, Aurelien; Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Inserm UMR1068 Marseille Cancerology Research Center, Institut Paoli-Calmettes, Marseille (France); Varoquaux, Arthur; Beschmout, Eva [Aix-Marseille University, Department of Medical Imaging, Conception Hospital, Marseille (France); Garrigue, Philippe; Guillet, Benjamin [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, Department of Radiopharmacy, La Timone and North University Hospital, Marseille (France); Montava, Marion; Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Guerin, Carole; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Gabriel, Sophie [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Morange, Isabelle; Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Barlier, Anne [Aix-Marseille, University, Laboratory of Biochemistry and Molecular Biology, Conception Hospital, Marseille (France); Loundou, Anderson [Aix-Marseille University, Department of Public Health, Marseille (France); Pacak, Karel [National Institutes of Health, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD (United States)

2016-07-15

Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of {sup 68}Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. {sup 68}Ga-DOTATATE, {sup 18}F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). {sup 68}Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than {sup 18}F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). {sup 68}Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on {sup 68}Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). {sup 68}Ga-DOTATATE PET/CT is the most sensitive tool in the

[7α-18F]fluoro-17α-methyl-5α-dihydrotestosterone: a ligand for androgen receptor-mediated imaging of prostate cancer

International Nuclear Information System (INIS)

Garg, Pradeep K.; Labaree, David C.; Hoyte, Robert M.; Hochberg, Richard B.

2001-01-01

We have synthesized a 18 F-labeled androgen, [7α- 18 F]fluoro-17α-methyl-5α-dihydrotestosterone, in a no-carrier-added radiosynthesis by exchange of 18 F- (tetrabutylammonium fluoride) with the 7β-tosyloxy of 17α-methyl-5α-dihydrotestosterone. The nonradioactive steroid binds with high affinity and specificity to the androgen receptor and binds poorly, if at all, to other steroid receptors and plasma sex hormone binding globulin. The 7α- 18 F-androgen concentrates markedly in the prostate of rats by an androgen receptor-dependent mechanism. It is likely that [7α- 18 F]fluoro-17α-methyl-5α-dihydrotestosterone will be an excellent positron emission tomography imaging agent for prostate cancer

Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain

Energy Technology Data Exchange (ETDEWEB)

Hartvig, P; Tedroff, J; Lindner, K J; Bjurling, P; Chang, C W; Laangstroem, B [Uppsala Univ. (Sweden); Tsukada, H [Central Research Lab., Hamamatsu Photonics Shizuoka, Osaka (Japan); Watanabe, Y [Dept. of Neuroscience, Osaka Bioscience Inst., Osaka (Japan)

1993-01-01

The regional brain kinetics following 5-hydroxy-L-([beta]-11 C)tryptophan and L-([beta]-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 [+-] 0.0007 (S. D) and 0.0121 [+-] 0.0010 min[sup -1] for 5-hydroxy-L-([beta]-11 C)tryptophan and L-([beta]-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-([beta]-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4 mg/kg of unlabelled compound. A decreased utilization rate of L-([beta]-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.

Improving the yield of 2-[18F]fluoro-2-deoxyglucose using a microwave cavity.

Science.gov (United States)

Taylor, M D; Roberts, A D; Nickles, R J

1996-07-01

We have investigated the use of a microwave cavity (Labwell AB, Sweden) to improve the radiochemical yield of 2-[18F]fluoro-2-deoxyglucose (2-[18F]FDG). After characterizing the heating properties of the cavity, three steps of the Hamacher 2-[18F]FDG synthesis which require heating--azeotropic distillation of the target water, nucleophilic substitution, and hydrolysis of the product--were investigated separately. The average radiochemical yield of 2-[18F]FDG for the microwave synthesis, using the phase transfer reagent tetrabutylammonium bicarbonate, was 62 +/- 4% (72 +/- 5%, decay corrected, synthesis time = 31 min).

Improving the yield of 2-[18F]fluoro-2-deoxyglucose using a microwave cavity

International Nuclear Information System (INIS)

Taylor, M.D.; Roberts, A.D.; Nickles, R.J.

1996-01-01

We have investigated the use of a microwave cavity (Labwell AB, Sweden) to improve the radiochemical yield of 2-[ 18 F]fluoro-2-deoxyglucose (2-[ 18 F]FDG). After characterizing the heating properties of the cavity, three steps of the Hamacher 2-[ 18 F]FDG synthesis which require heating--azeotropic distillation of the target water, nucleophilic substitution, and hydrolysis of the product--were investigated separately. The average radiochemical yield of 2-[ 18 F]FDG for the microwave synthesis, using the phase transfer reagent tetrabutylammonium bicarbonate, was 62 ± 4% (72 ± 5%, decay corrected, synthesis time = 31 min)

Metabolic liver function in humans measured by 2-(18)F-fluoro-2-deoxy-D-galactose PET/CT-reproducibility and clinical potential

DEFF Research Database (Denmark)

Bak-Fredslund, Kirstine P; Lykke Eriksen, Peter; Munk, Ole L

2017-01-01

Background: PET/CT with the radioactively labelled galactose analogue 2-18F-fluoro-2-deoxy-D-galactose (18F-FDGal) can be used to quantify the hepatic metabolic function and visualise regional metabolic heterogeneity. We determined the day-to-day variation in humans with and without liver disease....... Furthermore, we examined whether the standardised uptake value (SUV) of 18F-FDGal from static scans can substitute the hepatic systemic clearance of 18F- FDGal (Kmet, mL blood/min/mL liver tissue/) quantified from dynamic scans as measure of metabolic function. Four patients with cirrhosis and six healthy...... subjects underwent two 18F-FDGal PET/CT scans within a median interval of 15 days for determination of day-to-day variation. The correlation between Kmet and SUV was examined using scan data and measured arterial blood concentrations of 18F-FDGal (blood samples) from 14 subjects from previous studies...

Regulation of Pleiotrophin and Fyn in the striatum of rats undergoing L-DOPA-induced dyskinesia.

Science.gov (United States)

Gomez, Gimena; Saborido, Mariano D; Bernardi, M Alejandra; Gershanik, Oscar S; Taravini, Irene R; Ferrario, Juan E

2018-02-14

L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats. We have also shown that both mRNA and protein levels of RPTPζ/β, a PTN receptor, were upregulated in the same experimental condition and expressed in striatal medium spiny neurons. The PTN-RPTPζ/β intracellular pathway has not been fully explored and it might be implicated in the striatal plastic changes triggered by L-DOPA treatment. RPTPζ/β is part of the postsynaptic density zone and modulates Fyn, a Src tyrosine kinase that regulates the NR2A and NR2B subunits of the NMDA receptor and has been singled out as a key molecule in the development of LID. In this study, we evaluated the changes in PTN and Fyn protein levels and Fyn phosphorylation status in the 6-OHDA rat model of PD rendered dyskinetic with L-DOPA. We found an increase in the number of PTN immunoreactive neurons, no changes in the amount of total Fyn but a significant increase in Fyn phosphorylation in the dorsolateral striatum of dyskinetic rats. Our results support the idea that both PTN and Fyn may be involved in the development of LID, further contributing to the understanding of its molecular mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and biological evaluation of 2-amino-6-[{sup 18}F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[{sup 18}F]FPCV) as a novel PET probe for imaging HSV1-tk reporter gene expression

Energy Technology Data Exchange (ETDEWEB)

Cai Hancheng [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100049 (China); Yin Duanzhi [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)], E-mail: chcbati@yahoo.com.cn; Zhang Lan [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Yang, Xiaofeng; Xu Xiaoyan; Liu Weiguo; Zheng Xuesheng [Institute of Brain Medical Science, Second affiliated Hospital, Medicine School of Zhejiang University, Hangzhou 310009 (China); Zhang Hong [Department of Nuclear Medicine, Second Affiliated Hospital, Zhejiang University Medical PET Center, Medicine School of Zhejiang University, Hangzhou 310009 (China); Wang Jing [Department of Nuclear Medicine, Second Affiliated Hospital, Zhejiang University Medical PET Center, Medicine School of Zhejiang University, Hangzhou 310009 (China); Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Xu Yuhong [Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Cheng Dengfeng; Zheng Mingqiang; Han Yanjiang; Wu Mingxing; Wang Yongxian [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)

2007-08-15

Introduction: 2-Amino-6-[{sup 18}F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[{sup 18}F]FPCV) was prepared via a one-step nucleophilic substitution and evaluated as a novel probe for imaging the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene. Methods: Log P of 6-[{sup 18}F]FPCV was calculated in octanol/phosphate-buffered saline (PBS). Stability studies were performed in PBS and bovine serum albumin (BSA). Cell uptake was performed at various time points in wild-type cells and transduced cells. For in vivo studies, tumors were grown in nude mice by inoculation with C6 cells, wild type and tk positive. The radiotracer was intravenously injected to animals, and micro-PET imaging was performed. Biodistribution of 6-[{sup 18}F]FPCV was performed on another group of animals at different time points. Results: Log P of 6-[{sup 18}F]FPCV was -0.517. 6-[{sup 18}F]FPCV was fairly stable in PBS and BSA at 6 h. The tracer uptake in C6-tk cells was 5.5-18.8 times higher than that in wild-type cells. The plasma half-life of 6-[{sup 18}F]FPCV was as follows: {alpha} t{sub 1/2}=1.2 min and {beta} t{sub 1/2}=73.7 min. The average ratio of tumor uptake between the transduced tumor and the wild-type tumor was 1.69 at 15 min. Conclusion: Biological evaluation showed that 6-[{sup 18}F]FPCV is a potential probe for imaging HSV1-tk gene expression. However, its in vivo defluorination may limit its application in PET imaging of gene expression.

Selective loss of bi-directional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and l-DOPA induced dyskinesia in mouse models.

Science.gov (United States)

Thiele, Sherri L; Chen, Betty; Lo, Charlotte; Gertler, Tracey S; Warre, Ruth; Surmeier, James D; Brotchie, Jonathan M; Nash, Joanne E

2014-11-01

Parkinsonian symptoms arise due to over-activity of the indirect striatal output pathway, and under-activity of the direct striatal output pathway. l-DOPA-induced dyskinesia (LID) is caused when the opposite circuitry problems are established, with the indirect pathway becoming underactive, and the direct pathway becoming over-active. Here, we define synaptic plasticity abnormalities in these pathways associated with parkinsonism, symptomatic benefits of l-DOPA, and LID. We applied spike-timing dependent plasticity protocols to cortico-striatal synapses in slices from 6-OHDA-lesioned mouse models of parkinsonism and LID, generated in BAC transgenic mice with eGFP targeting the direct or indirect output pathways, with and without l-DOPA present. In naïve mice, bidirectional synaptic plasticity, i.e. LTP and LTD, was induced, resulting in an EPSP amplitude change of approximately 50% in each direction in both striatal output pathways, as shown previously. In parkinsonism and dyskinesia, both pathways exhibited unidirectional plasticity, irrespective of stimulation paradigm. In parkinsonian animals, the indirect pathway only exhibited LTP (LTP protocol: 143.5±14.6%; LTD protocol 177.7±22.3% of baseline), whereas the direct pathway only showed LTD (LTP protocol: 74.3±4.0% and LTD protocol: 63.3±8.7%). A symptomatic dose of l-DOPA restored bidirectional plasticity on both pathways to levels comparable to naïve animals (Indirect pathway: LTP protocol: 124.4±22.0% and LTD protocol: 52.1±18.5% of baseline. Direct pathway: LTP protocol: 140.7±7.3% and LTD protocol: 58.4±6.0% of baseline). In dyskinesia, in the presence of l-DOPA, the indirect pathway exhibited only LTD (LTP protocol: 68.9±21.3% and LTD protocol 52.0±14.2% of baseline), whereas in the direct pathway, only LTP could be induced (LTP protocol: 156.6±13.2% and LTD protocol 166.7±15.8% of baseline). We conclude that normal motor control requires bidirectional plasticity of both striatal outputs

Biochemical characterization of a novel tyrosine phenol-lyase from Fusobacterium nucleatum for highly efficient biosynthesis of l-DOPA.

Science.gov (United States)

Zheng, Ren-Chao; Tang, Xiao-Ling; Suo, Hui; Feng, Li-Lin; Liu, Xiao; Yang, Jian; Zheng, Yu-Guo

2018-05-01

Tyrosine phenol-lyase (TPL) catalyzes the reversible cleavage of l-tyrosine to phenol, pyruvate and ammonia. When pyrocatechol is substituted for phenol, l-dihydroxyphenylalanine (l-DOPA) is produced. The TPL-catalyzed route was regarded as the most economic process for l-DOPA production. In this study, a novel TPL from Fusobacterium nucleatum (Fn-TPL) was successfully overexpressed in Escherichia coli and screened for l-DOPA synthesis with a specific activity of 2.69Umg -1 . Fn-TPL was found to be a tetramer, and the optimal temperature and pH for α, β-elimination of l-tyrosine was 60°C and pH 8.5, respectively. The enzyme showed broad substrate specificity toward natural and synthetic l-amino acids. Kinetic analysis suggested that the k cat /K m value for l-tyrosine decomposition was much higher than that for l-DOPA decomposition, while Fn-TPL exhibited similar catalytic efficiency for synthesis of l-tyrosine and l-DOPA. With whole cells of recombinant E. coli as biocatalyst, l-DOPA yield reached 110gL -1 with a pyrocatechol conversion of 95%, which was comparable to the reported highest level. The results demonstrated the great potential of Fn-TPL for industrial production of l-DOPA. Copyright © 2017 Elsevier Inc. All rights reserved.

Plasma dihydroxyphenylalanine (DOPA) is independent of sympathetic activity in humans

DEFF Research Database (Denmark)

Eldrup, E; Christensen, N J; Andreasen, J

1989-01-01

in diabetic patients with autonomic neuropathy compared to diabetics without neuropathy, whereas baseline plasma DOPA concentrations were similar in the three groups investigated: 6.55 (5.03-7.26, median [interquartile range], n = 8) nmol l-1 in diabetics with neuropathy, 7.41 (5.79-7.97, n = 8) nmol l-1...... in diabetics without neuropathy, and 6.85 (5.58-7.36, n = 8) nmol l-1 in controls. No relationship was obtained between baseline values of plasma NE and plasma DOPA. Plasma DOPA did not change in the upright position, whereas plasma NE increased significantly. Our results indicate that plasma DOPA...... is not related to sympathetic activity and may be of non-neuronal origin....

A specific radioenzymatic assay for dihydroxyphenylalanine (DOPA). Plasma DOPA may be the precursor of urine free dopamine

International Nuclear Information System (INIS)

Brown, M.J.; Dollery, C.T.

1981-01-01

A sensitive radioenzymatic assay was developed, in which DOPA is enzymatically decarboxylated to dopamine and the latter converted to [ 3 H]-methoxytryamine in the presence of [ 3 H]-S-adenosyl-L-methionine and catechol-o-methyltransferase. The assay was specific for DOPA, and was sensitive to 50 pg/ml. Endogenous DOPA was found to be present in the plasma of eight human volunteers at a concentration of 10.46 +- 2.42 nmol/l. Simultaneous urine collections in the same subjects showed a free dopamine excretion of 68.88 +- 17.70 nmol/h. There was a significant correlation (P < 0.01) between plasma DOPA concentration and urine free dopamine excretion (r = 0.84). After the oral administration of 250 mg levodopa, plasma DOPA and urine dopamine both increased by a similar proportion (98 +- 8.4-fold, and 93.4 +- 6.9-fold respectively). These compare with an increase in plasma dopamine of only 26 +- 15-fold (P<0.01). Following the oral dose of DOPA, the increase in plasma DOPA, but not plasma dopamine, could account for the increase in urine dopamine. The calculated clearance of plasma DOPA by renal decarboxylation to dopamine was 114 +- 20 ml/min. This is not significantly different from the apparent clearance of endogenous DOPA by renal decarboxylation to dopamine, and suggests that there is adequate renal decarboxylase activity for DOPA to be the precursor for renal dopamine formation. (author)

L-tyrosine and L-DOPA as hormone-like regulators of melanocytes functions

Science.gov (United States)

Slominski, Andrzej; Zmijewski, Michal; Pawelek, John

2011-01-01

Summary Evidence reveals that L-tyrosine and L-DOPA, besides serving as substrates and intermediates of melanogenesis, are also bioregulatory agents acting not only as inducers and positive regulators of melanogenesis but also as regulators of other cellular functions. These can be mediated through action on specific receptors or through non-receptor mediated mechanisms. The substrate induced (L-tyrosine and/or L-DOPA) melanogenic pathway would autoregulate itself as well as it would regulate the melanocyte functions through activity of its structural or regulatory proteins and through intermediates of melanogenesis and melanin itself. Dissection of regulatory and autoregulatory elements of this process may elucidate how substrate induced autoregulatory pathways have evolved from prokaryotic or simple eukaryotic organisms to complex systems in vertebrates. This could substantiate older theory proposing that receptors for amino-acid derived hormones arose from the receptors for those amino acids, and that nuclear receptors evolved from primitive intracellular receptors binding nutritional factors or metabolic intermediates. PMID:21834848

EVALUATING THE ACCUMULATION TREND OF L-DOPA IN DARK-GERMINATED SEEDS AND SUSPENSION CULTURES OF Phaseolus vulgaris L. BY AN EFFICIENT UV-SPECTROPHOTOMETRIC METHOD

Directory of Open Access Journals (Sweden)

Samira Rahmani-Nezhad

Full Text Available Seed germination and plant cell cultures provide an alternative mean for producing secondary metabolites. The present study is an attempt to evaluate the effect of seed dark germination and some elicitors and precursors on the production of L-DOPA in Phaseolus vulgaris L. Callus cultured on Murashige and Skoog medium supplemented with various concentrations of different plant growth regulators. L-DOPA produced was quantified by UV-spectrophotometric method. In this study, a user-friendly, quick, and economical UV-spectrophotometric method was described to determine L-DOPA content in extracts from 33 biotypes of Phaseolus vulgaris L. The method is based on the nitrosation of L-DOPA to form a yellow solution and then formation of a red solution by adding base which is measurable at 470 nm. According to our statistical studies, this method showed high efficiency and selectivity for quantitative determination of L-DOPA in herbal extracts from dried plant seeds, dark-germinated seeds and callus cultures. L-DOPA content in dark-germinated seeds and suspension cultures increased significantly to approximately several-fold compared to the control. The implication from this study is that elicitor treatment and precursor feeding of Phaseolus vulgaris L. can significantly improve the parkinson’s relevant L-DOPA content.

Maladaptive synaptic plasticity in L-DOPA-induced dyskinesia

Directory of Open Access Journals (Sweden)

Qiang Wang

2016-12-01

Full Text Available The emergence of L-DOPA-induced dyskinesia (LID in patients with Parkinson disease (PD could be due to maladaptive plasticity of corticostriatal synapses in response to L-DOPA treatment. A series of recent studies has revealed that LID is associated with marked morphological plasticity of striatal dendritic spines, particularly cell type-specific structural plasticity of medium spiny neurons (MSNs in the striatum. In addition, evidence demonstrating the occurrence of plastic adaptations, including aberrant morphological and functional features, in multiple components of cortico-basal ganglionic circuitry, such as primary motor cortex (M1 and basal ganglia (BG output nuclei. These adaptations have been implicated in the pathophysiology of LID. Here, we briefly review recent studies that have addressed maladaptive plastic changes within the cortico-BG loop in dyskinetic animal models of PD and patients with PD.

L-DOPA therapy interferes with urine catecholamine analysis in children with suspected neuroblastoma: a case series.

Science.gov (United States)

Kelly, Alison U; Srivastava, Rajeev; Dow, Ellie; Davidson, D Fraser

2017-09-01

Neuroblastoma is the most common solid extracranial malignancy diagnosed in childhood. Clinical presentation is variable, and metastatic disease is common at diagnosis. Analyses of urinary catecholamines and their metabolites are commonly requested as a first-line investigation when clinical suspicion exists. Levodopa (L-Dopa) therapy is utilized as a treatment for a number of disorders in childhood, including Dopa-responsive dystonia. Neuroblastoma may mimic some of the clinical features of this disorder. L-Dopa can interfere with analysis of urinary catecholamines and their metabolites and complicate the interpretation of results. We present the cases of three children who were prescribed L-dopa at the time of analysis of urinary catecholamines and metabolites as a screen for neuroblastoma, but who did not have the disease. Comparison of their results with those from cases with true neuroblastoma reveal that it is impossible to reliably distinguish true neuroblastoma from L-Dopa therapy using these tests. We recommend that patients should be off L-dopa therapy, if possible when these tests are performed. These cases illustrate the importance of providing clinical details and drug history to the laboratory in order to avoid diagnostic confusion.

1-[[sup 18]F]fluoro-2-propanol p-toluenesulfonate: a synthon for the preparation of N-([[sup 18]F]fluoroisopropyl)amines

Energy Technology Data Exchange (ETDEWEB)

Groot, T.J. de; Elsinga, P.H.; Visser, G.M.; Vaalburg, W. (Groningen Univ. (Netherlands). PET Center and GCCS)

1992-11-01

The new radiochemical synthon 1-[[sup 18]F]fluoro-2-propanol p-toluenesulfonate is prepared with a radiochemical yield of 45% [corrected for decay to beginning of synthesis, synthesis time 40 min]. This compound is used to prepare the [[sup 18]F]fluoroisopropyl-alkylated derivatives of benzylamine and norephedrine with a yield of 7 and 2% respectively, (synthesis time 90 min). This alkylation reaction a good perspective for the preparation of [[sup 18]F]fluoro-labelled analogues of [beta][sub 1]-adrenergic receptor binding ligands for PET. (Author).

Difference in prognostic significance of maximum standardized uptake value on [18F]-fluoro-2-deoxyglucose positron emission tomography between adenocarcinoma and squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Tsutani, Yasuhiro; Miyata, Yoshihiro; Misumi, Keizo; Ikeda, Takuhiro; Mimura, Takeshi; Hihara, Jun; Okada, Morihito

2011-01-01

This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n=132) or squamous cell carcinoma (n=44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P 6.95 (P=0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P<0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P<0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P=0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P=0.001). Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung. (author)

Positron-labeled antioxidant 6-deoxy-6-[{sup 18}F]fluoro-L-ascorbic acid: Increased uptake in transient global ischemic rat brain

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Fumihiko; Shibata, Shigenobu; Watanabe, Shigenori; Masuda, Kouji; Maeda, Minoru

1996-05-01

The in vivo uptake and distribution of 6-deoxy-6-[{sup 18}F]fluoro-L-ascorbic acid ({sup 18}F-DFA) were investigated in rat brains following postischemic reperfusion. Global cerebral ischemia was induced in male Wistar rats for 20 min by occlusion of four major arteries. Two time points were chosen for {sup 18}F-DFA injection to rats subjected to cerebral ischemia, at the start of recirculation and 5 days following recirculation. The rats were then killed at 2 h after tail-vein administration of {sup 18}F-DFA and tissue radioactivity concentration was determined. Increased uptake of radioactivity in particular brain regions, including the cerebral cortex, hypothalamus, and amygdala following injection of {sup 18}F-DFA, compared to the sham-operated control, was observed 5 days after reperfusion. Similar results were also obtained in in vitro experiments using brain slices. Abnormal in vivo accumulation of {sup 45}Ca, a marker of regional postischemic injury, was observed in these brain regions in tissue dissection experiments. Furthermore, metabolite analysis of nonradioactive DFA using {sup 19}F-NMR showed that DFA remained intact in the postischemic reperfusion brain. The present results indicate that {sup 18}F-DFA increasingly accumulates in damaged regions of postischemic reperfusion brain.

Estimation of L-dopa from Mucuna pruriens LINN and formulations containing M. pruriens by HPTLC method.

Science.gov (United States)

Modi, Ketan Pravinbhai; Patel, Natvarlal Manilal; Goyal, Ramesh Kishorilal

2008-03-01

A selective, precise, and accurate high-performance thin-layer chromatographic (HPTLC) method has been developed for the analysis of L-dopa in Mucuna pruriens seed extract and its formulations. The method involves densitometric evaluation of L-dopa after resolving it by HPTLC on silica gel plates with n-butanol-acetic acid-water (4.0+1.0+1.0, v/v) as the mobile phase. Densitometric analysis of L-dopa was carried out in the absorbance mode at 280 nm. The relationship between the concentration of L-dopa and corresponding peak areas was found to be linear in the range of 100 to 1200 ng/spot. The method was validated for precision (inter and intraday), repeatability, and accuracy. Mean recovery was 100.30%. The relative standard deviation (RSD) values of the precision were found to be in the range 0.64-1.52%. In conclusion, the proposed TLC method was found to be precise, specific and accurate and can be used for identification and quantitative determination of L-dopa in herbal extract and its formulations.

Tratamento da síndrome parkinsoniana pelo L-dopa

Directory of Open Access Journals (Sweden)

Roberto Melaragno

1971-12-01

Full Text Available O trabalho refere o tratamento com L-Dopa de 33 pacientes internados, sendo 19 homens e 14 mulheres. Os casos foram agrupados, segundo uma classificação esquemática, em leves, moderados, intensos e severos. As idades dos pacientes, previamente operados ou não, variaram de 42 a 78 anos. O esquema de medicação constou de administração de L-Dopa na dose inicial de 500 mg associado a um inibidor da MAO. A dose de L-Dopa era elevada de 500 mg cada 3 ou 4 dias, segundo a tolerância de cada paciente. Todos os sintomas dependentes, direta ou indiretamente, da rigidez tiveram melhoras mais nítidas em relação aos tremores. Durante a administração do medicamento os teores sangüíneos de ácido úrico e uréia, mostraram tendência para se elevar; a reserva alcalina, pelo contrário, tendeu para a diminuição; o hemograma revelou muitas vezes eosinofilia por vezes intensa. Os efeitos colaterais foram catalogados em dois tipos — efeitos adrenérgicos e efeitos dopaminérgicos — correspondentes a duas fases: uma primeira, de pequena duração, na qual foram usados concomitantemente o L-Dopa e um inibidor da MAO, surgindo cefaléia hipertensão arterial paroxística, rubor facial, sudorese, tenesmo vesical e angina pectoris; numa segunda fase surgiram os efeitos colaterais ditos dopaminérgicos, proporcionais à gravidade clínica do caso, cujas manifestações principais foram hipotensão arterial, sudorese fria, arritmia cardíaca e lipotimia. As complicações clínicas gerais eram representados habitualmente por anorexia, obstipação intestinal, náuseas, vômitos, discretas alterações do estado psíquico com depressão e euforia. Dentre as complicações neurológicas foram assinalados o estado parkinsonóide, discinesias e acatisia.

Production process validation of 2-[18F]-fluoro-2-deoxy-D-glucose

International Nuclear Information System (INIS)

Cantero, Miguel; Iglesias, Rocio; Aguilar, Juan; Sau, Pablo; Tardio, Evaristo; Narrillos, Marcos

2003-01-01

The main of validation of production process of 2-[18F]-fluoro-2-deoxi-D-glucose (FDG) was to check: A) equipment's and services implicated in the production process were correctly installed, well documented, and worked properly, and B) production of FDG was done in a repetitive way according to predefined parameters. The main document was the Validation Master Plan, and steps were: installation qualification, operation qualification, process qualification and validation report. After finalization of all tests established in qualification steps without deviations, we concluded that the production process was validated because is done in a repetitive way according predefined parameters (Au)

Effect of l-DOPA on local field potential relationship between the pedunculopontine nucleus and primary motor cortex in a rat model of Parkinson's disease.

Science.gov (United States)

Geng, Xiwen; Wang, Xuenan; Xie, Jinlu; Zhang, Xiao; Wang, Xiusong; Hou, Yabing; Lei, Chengdong; Li, Min; Han, Hongyu; Yao, Xiaomeng; Zhang, Qun; Wang, Min

2016-12-15

Levodopa (l-DOPA) has been proved to reverse the pathologic neuron activities in many brain regions related to Parkinson's disease (PD). But little is known about the effect of l-DOPA on the altered electrophysiological coherent activities between pedunculopontine nucleus (PPN) and motor cortex. To investigate this, local field potentials (LFPs) of PPN and primary motor cortex (M1) were recorded simultaneously in control, 6-hydroxydopamine lesioned and lesioned rats with l-DOPA chronic treatment. The results revealed that in resting state, chronic l-DOPA treatment could correct the suppressed power of LFPs in PPN and M1 in low-frequency band (1-7Hz) and the enhanced power in high-frequency band (7-70Hz in PPN and 12-70Hz in M1) of lesioned rats. In locomotor state, l-DOPA treatment could correct the alterations in most of frequency bands except the δ band in PPN and α band in M1. Moreover, l-DOPA could also reverse the altered coherent relationships caused by dopamine depletion in resting state between PPN and M1 in β band. And in locomotor state, l-DOPA had therapeutic effect on the alterations in δ and β bands but not in the α band. These findings provide evidence that l-DOPA can reverse the altered LFP activities in PPN and M1 and their relationships in a rat model of PD, which contributes to better understanding the electrophysiological mechanisms of the pathophysiology and therapy of PD. Copyright © 2016. Published by Elsevier B.V.

Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum, measured using in vivo microdialysis and PET

International Nuclear Information System (INIS)

Opacka-Juffry, J.; Hume, S. P.; Ashworth, S.; Ahier, R. G.

1997-01-01

Putative modulatory effects of L-3,4-dihydroxyphenylalanine (L-DOPA) on D2 dopamine receptor function in the striatum of anaesthetized rats were investigated using both in vivo microdialysis and positron emission tomography (PET) with carbon-11 labelled raclopride as a selective D2 receptor ligand. A single dose of L-DOPA (20 or 100 mg/kg i.p.) resulted in an increase in [ 11 C]raclopride binding potential which was also observed in the presence of the central aromatic decarboxylase inhibitor NSD 1015, confirming that the effect was independent of dopamine. This L-DOPA evoked D2 receptor sensitization was abolished by a prior, long-term administration of L-DOPA in drinking water (5 weeks, 170 mg/kg/day). In the course of acute L-DOPA treatment (20 mg/kg), extracellular GABA levels were reduced by ∼20 % in the globus pallidus. It is likely that L-DOPA sensitising effect on striatal D2 receptors, as confirmed by PET, may implicate striato-pallidal neurones, hence a reduced GABA-ergic output in the projection area. Since the L-DOPA evoked striatal D2 receptor supersensitivity habituates during long-term treatment, the effects reported here may contribute to the fluctuations observed during chronic L-DOPA therapy in Parkinson's disease. (author)

Use of fluorine-18 free of carrier for the synthesis of 2-[{sup 18} F]-fluoro-2-deoxy-d-glucose by nucleophilic substitution; Uso del fluor-18 libre de portador para la sintesis de la 2-[{sup 18} F]-fluoro-2-deoxi-d-glucosa por sustitucion nucleofilica

Energy Technology Data Exchange (ETDEWEB)

Garcia S, I; Ramirez, F M

1990-11-15

Preliminary studies on the synthesis of 2 - [{sup 18} F]-fluoro-2-deoxy-d-glucose (2 - [{sup 18} F]-FDG) were carried out by means of the nucleophilic method proposed by K. Hamacher and the {sup 18} F obtained in the Nuclear Reactor TRIGA Mark III of the Nuclear Center of Mexico. For the control of radiochemical quality it was used the chromatography technique in paper and silica gel with 4 solvent systems. The identification of the marked species with {sup 18} F was carried out by means of comparison of its Rf with the Rf of the obtained not radioactive species, using the same synthesis method. (Author)

l-Dopa responsiveness is associated with distinctive connectivity patterns in advanced Parkinson's disease.

Science.gov (United States)

Akram, Harith; Wu, Chengyuan; Hyam, Jonathan; Foltynie, Thomas; Limousin, Patricia; De Vita, Enrico; Yousry, Tarek; Jahanshahi, Marjan; Hariz, Marwan; Behrens, Timothy; Ashburner, John; Zrinzo, Ludvic

2017-06-01

Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to l-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3 × 3 × 2.5 mm 3 voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an l-dopa challenge. False discovery rate-corrected P was set at basal ganglia resting-state functional connectivity patterns associated with different degrees of l-dopa responsiveness in patients with advanced Parkinson's disease. l-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Parametric imaging of {sup 18}F-fluoro-3-deoxy-3-l-fluorothymidine PET data to investigate tumour heterogeneity

Energy Technology Data Exchange (ETDEWEB)

Veronese, M. [University of Padova, Department of Information Engineering (DEI), Padova (Italy); King' s College London, Department of Neuroimaging, Institute of Psychiatry, London (United Kingdom); Rizzo, G.; Bertoldo, A. [University of Padova, Department of Information Engineering (DEI), Padova (Italy); Aboagye, E.O. [Imperial College London, Comprehensive Cancer Imaging Centre, London (United Kingdom)

2014-09-15

[{sup 18}F]Fluoro-3'-deoxy-3'-l-fluorothymidine ([{sup 18}F]FLT) is a tissue proliferation marker which has been widely validated as a tumour-specific imaging tracer for PET. [{sup 18}F]FLT uptake in breast cancer is generally quantified at the region level or through first-order statistical descriptors (mean or maximum value), approaches that ignore the known complexity and heterogeneity of cancer tissues. Our aims were: (1) to validate a robust and reproducible voxel-wise approach to the quantification of [{sup 18}F]FLT PET data in breast cancer patients, and (2) to exploit the entire distribution of the [{sup 18}F]FLT retention estimates and their variability in the tumour region for the prediction of early treatment response. The dataset was derived from 15 patients with stage II-IV breast cancer, scanned twice before chemotherapy and once 1 week after therapy. Using RECIST criteria (after 60 days) nine patients were categorized as responders or nonresponders to treatment. Kinetic modelling (compartmental modelling, Patlak analysis and spectral analysis with iterative filter), tissue-to-plasma ratio and standardized uptake value were applied at the voxel level. Test-retest estimates were used to assess reproducibility and reliability of the [{sup 18}F]FLT uptake values before and after therapy for responder/nonresponder prediction. All the methods provided a measure of [{sup 18}F]FLT uptake that was reliable and reproducible with ICC >0.94. Moreover, a very strong correlation was found among the methods (R {sup 2} > 0.81). All the methods provided a limited number of outliers (<20 % in tumour), with the exception of compartmental modelling (>25 %) which was therefore excluded from the prediction analysis. Differences between before and after therapy in mean voxel-wise uptake in tumour did not allow a complete responder/nonresponder classification. In contrast, considering the full estimate distributions within the tumour (changes in median and mode

Production process validation of 2-[18F]-fluoro-2-deoxy-D-glucose

International Nuclear Information System (INIS)

Cantero, Miguel; Iglesias, Rocio; Aguilar, Juan; Sau, Pablo; Tardio, Evaristo; Narrillos, Marcos

2003-01-01

The aim of production process validation of 2-[18F]-fluoro-2-deoxi-D-glucose (FDG) was to check: A) equipments and services implicated in the production process were correctly installed, well documented, and worked properly, and B) production of FDG was done in a repetitive way according to predefined parameters. The main document was the Validation Master Plan, and steps were: installation qualification, operational qualification, performance qualification and validation final report. After finalization of all tests established in qualification steps without deviations, we concluded that the production process was validated because consistently produced FDG meeting its pre-determined specifications and quality characteristics (Au)

Quantitative Determination of L-DOPA in Seeds of Mucuna Pruriens Germplasm by High Performance Thin Layer Chromatography.

Science.gov (United States)

Raina, Archana P; Khatri, Renu

2011-07-01

Mucuna pruriens Linn. is an important medicinal plant used for treatment of Parkinson's disease and many others in ancient Indian medical system. L-DOPA extracted from seeds of Mucuna is a constituent of more than 200 indigenous drug formulations and is more effective as drug than the synthetic counterpart. A densitometric high performance thin-layer chromatographic (HPTLC) method was developed for quantification of L-DOPA content present in the seeds extract. The method involves separation of L-DOPA on precoated silica gel 60 GF(254) HPTLC plates using a solvent system of n-butanol-acetic-acid-water (4:1:1, v/v) as the mobile phase. Quantification was done at 280 nm using absorbance reflectance mode. Linearity was found in the concentration range of 100 to 1000 ng/spot with the correlation coefficient value of 0.9980. The method was validated for accuracy, precision and repeatability. Mean recovery was 100.89%. The LOD and LOQ for L-DOPA determination were found to be 3.41 ng/spot and 10.35 ng/spot respectively. The proposed HPTLC method was found to be precise, specific and accurate for quantitative determination of L-DOPA. It can be used for rapid screening of large germplasm collections of Mucuna pruriens for L-DOPA content. The method was used to study variation in fifteen accessions of Mucuna germplasm collected from different geographical regions.

Novel L-Dopa and dopamine prodrugs containing a 2-phenyl-imidazopyridine moiety.

Science.gov (United States)

Denora, Nunzio; Laquintana, Valentino; Lopedota, Angela; Serra, Mariangela; Dazzi, Laura; Biggio, Giovanni; Pal, Dhananjay; Mitra, Ashim K; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano

2007-07-01

The aim of this study was to gain insight into the feasibility of enhancing the delivery of L-Dopa and dopamine to the brain by linking these neurotransmitters and L-Dopa ethyl ester to 2-phenyl-3-carboxymethyl-imidazopyridine compounds giving rise to the so-called Dopimid compounds. A number of Dopimid compounds were synthesized and both stability and binding studies to dopaminergic and benzodiazepine receptors were performed. To evaluate whether Dopimid compounds are P-gp substrates, [(3)H]ritonavir uptake experiments and bi-directional transport studies on confluent MDCKII-MDR1 monolayers were carried out. The brain penetration properties of Dopimid compounds were estimated by the Clark's computational model and evaluated by investigation of their transport across BBMECs monolayers. The dopamine levels following the intraperitoneal administration of the selected Dopimid compounds were measured in vivo by using brain microdialysis in rat. Tested compounds were adequately stable in solution buffered at pH 7.4 but undergo faster cleavage in dilute rat serum at 37 degrees C. Receptor binding studies showed that Dopimid compounds are essentially devoid of affinity for dopaminergic and benzodiazepine receptors. [(3)H]ritonavir uptake experiments indicated that selected Dopimid compounds, like L-Dopa and dopamine hydrochloride, are not substrates of P-gp and it was also confirmed by bi-directional transport experiments across MDCKII-MDR1 monolayers. By Clark's model a significant brain penetration was deduced for L-Dopa ethyl ester and dopamine derivatives. Transport studies involving BBMECs monolayers indicated that some of these compounds should be able to cross the BBB. Interestingly, the rank order of apparent permeability (P (app)) values observed in these assays parallels that calculated by the computational approach. Brain microdialysis experiments in rat showed that intraperitoneal acute administration of some Dopimid compounds induced a dose-dependent increase

Effects of L-DOPA on aggressive behavior and central monoaminergic activity in the lizard Anolis carolinensis, using a new method for drug delivery.

Science.gov (United States)

Höglund, Erik; Korzan, Wayne J; Watt, Michael J; Forster, Gina L; Summers, Tangi R; Johannessen, Helga Falch; Renner, Kenneth J; Summers, Cliff H

2005-01-06

The dopamine (DA) precursor, L-DOPA (500 microg), was injected into living crickets, which were ingested (one each) by adult male Anolis carolinensis. This method of delivery elevated plasma L-DOPA and DA concentrations by approximately 1000-fold. In contrast, plasma epinephrine (Epi) and norepinephrine (NE) were not influenced by L-DOPA treatment, although they were elevated following the consumption of the cricket. Lizards that ingested L-DOPA treated crickets had elevated L-DOPA in all brain regions measured, with DA and/or DOPAC also increased significantly in most brain regions studied. Despite increased DA levels in the striatum and nucleus accumbens as a response to L-DOPA, the treatment had no influence on general motor activity. Central serotonin, NE, and Epi systems were not affected in any brain region by oral L-DOPA treatment. In addition, aggression was inhibited by this dose of L-DOPA, even though there was no effect on serotonergic systems. This is surprising because controlling aggressive behavior is usually considered the province of serotonergic activity. Aggression was measured before and after treatment, and while saline-treated lizards retained the full vigor of aggressive activity, those fed a cricket injected with L-DOPA were only one-third as aggressive after treatment. As L-DOPA treatment did not affect general motor activity, the effect appears to be directly associated with aggression. This is supported by the observation that L-DOPA treatment delayed latency to eyespot darkening, which predicts the latency to aggression.

In-vivo studies by positron emission tomography of the pharmacokinetics of L-6-F-18-fluorodopa

International Nuclear Information System (INIS)

Pate, B.D.; Calne, D.B.; Hewitt, K.A.; Ruth, T.J.; Adam, M.J.

1989-01-01

Positron emission tomography has been used to study the pharmacokinetics of fluorine-18-labelled L-6-fluorodopa in the brains of cynomolgus monkey subjects. The protocol for each experiment consisted of two series of twelve 10-minutes scans, conducted one after the other with the monkey in the same position, with an inhibitor acting at a specific stage of the kinetics, administered before the second series. Subtractions of the two scan series (following correction for activity residue in the second scans) then gave a quantitative measure of the effects produced by the inhibitor. The inhibitors studied include NSD 1015 (decarboxylase inhibitor), chlorgyline (MAO-A inhibitor), deprenyl (MAO-B inhibitor), pargyline (inhibitor of both MAO-A and MAO-B), U-0521 (COMT inhibitor), and reserpine (vesicular storage inhibitor). The results show that L-6-fluorodopa is a substrate for dopa decarboxylase, while fluorodopamine is a substrate for both MAO-A and MAO-B, and for COMT. Vesicular storage (inhibited by reserpine) was shown also to be essential for concentration of the activity into striatal images

Use of fluorine-18 free of carrier for the synthesis of 2-[18 F]-fluoro-2-deoxy-d-glucose by nucleophilic substitution

International Nuclear Information System (INIS)

Garcia S, I.; Ramirez, F.M.

1990-11-01

Preliminary studies on the synthesis of 2 - [ 18 F]-fluoro-2-deoxy-d-glucose (2 - [ 18 F]-FDG) were carried out by means of the nucleophilic method proposed by K. Hamacher and the 18 F obtained in the Nuclear Reactor TRIGA Mark III of the Nuclear Center of Mexico. For the control of radiochemical quality it was used the chromatography technique in paper and silica gel with 4 solvent systems. The identification of the marked species with 18 F was carried out by means of comparison of its Rf with the Rf of the obtained not radioactive species, using the same synthesis method. (Author)

Radiolysis of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) and the role of ethanol and radioactive concentration

Energy Technology Data Exchange (ETDEWEB)

Jacobson, Mark S. [Division of Nuclear Medicine, Mayo Clinic, Rochester, MN (United States)], E-mail: jacobson.mark17@mayo.edu; Dankwart, Heather R. [Division of Nuclear Medicine, Mayo Clinic, Rochester, MN (United States); Mahoney, Douglas W. [Division of Biostatistics, Mayo Clinic, Rochester, MN (United States)

2009-06-15

Radiolysis is the process by which radioactively labeled compounds degrade. Many positron emission tomography (PET) radiopharmaceuticals produced with high radioactive concentrations and specific activities exhibit low radiochemical purity because of radiolysis. Little data exist that describe the radiolytic decomposition of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG). The objective of our study was to profile the degradation of [{sup 18}F]FDG at various radioactive concentrations by measuring radiochemical purity at different time intervals and to study the effects of ethanol, a well-known reductant stabilizer of [{sup 18}F]FDG preparations.

The role of L-DOPA on melanization and mycelial production in Malassezia furfur.

Directory of Open Access Journals (Sweden)

Sirida Youngchim

Full Text Available Melanins are synthesized by organisms of all biological kingdoms and comprise a heterogeneous class of natural pigments. Certain of these polymers have been implicated in the pathogenesis of several important human fungal pathogens. This study investigated whether the fungal skin pathogen Malassezia furfur produces melanin or melanin-like compounds. A melanin-binding monoclonal antibody (MAb labelled in vitro cultivated yeast cells of M. furfur. In addition, melanization of Malassezia yeasts and hyphae was detected by anti-melanin MAb in scrapings from patients with pityriasis versicolor. Treatment of Malassezia yeasts with proteolytic enzymes, denaturant and concentrated hot acid yielded dark particles and electron spin resonance spectroscopy revealed that these particles contained a stable free radical compound, consistent with their identification as melanins. Malassezia yeasts required phenolic compounds, such as L-DOPA, in order to synthesize melanin. L-DOPA also triggered hyphal formation in vitro when combined with kojic acid, a tyrosinase inhibitor, in a dose-dependent manner. In this respect, L-DOPA is thought to be an essential substance that is linked to both melanization and yeast-mycelial transformation in M. furfur. In summary, M. furfur can produce melanin or melanin-like compounds in vitro and in vivo, and the DOPA melanin pathway is involved in cell wall melanization.

The Role of L-DOPA on Melanization and Mycelial Production in Malassezia Furfur

Science.gov (United States)

Youngchim, Sirida; Nosanchuk, Joshua D.; Pornsuwan, Soraya; Kajiwara, Susumu; Vanittanakom, Nongnuch

2013-01-01

Melanins are synthesized by organisms of all biological kingdoms and comprise a heterogeneous class of natural pigments. Certain of these polymers have been implicated in the pathogenesis of several important human fungal pathogens. This study investigated whether the fungal skin pathogen Malassezia furfur produces melanin or melanin-like compounds. A melanin-binding monoclonal antibody (MAb) labelled in vitro cultivated yeast cells of M. furfur. In addition, melanization of Malassezia yeasts and hyphae was detected by anti-melanin MAb in scrapings from patients with pityriasis versicolor. Treatment of Malassezia yeasts with proteolytic enzymes, denaturant and concentrated hot acid yielded dark particles and electron spin resonance spectroscopy revealed that these particles contained a stable free radical compound, consistent with their identification as melanins. Malassezia yeasts required phenolic compounds, such as L-DOPA, in order to synthesize melanin. L-DOPA also triggered hyphal formation in vitro when combined with kojic acid, a tyrosinase inhibitor, in a dose-dependent manner. In this respect, L-DOPA is thought to be an essential substance that is linked to both melanization and yeast-mycelial transformation in M. furfur. In summary, M. furfur can produce melanin or melanin-like compounds in vitro and in vivo, and the DOPA melanin pathway is involved in cell wall melanization. PMID:23762233

Automatic synthesis of 16α-[18F]fluoro-17β-estradiol using a cassette-type [18F]fluorodeoxyglucose synthesizer

International Nuclear Information System (INIS)

Mori, Tetsuya; Kasamatsu, Shingo; Mosdzianowski, Christoph; Welch, Michael J.; Yonekura, Yoshiharu; Fujibayashi, Yasuhisa

2006-01-01

16α-[ 18 F]fluoro-17β-estradiol ([ 18 F]FES) is a radiotracer for imaging estrogen receptors by positron emission tomography. We developed a clinically applicable automatic preparation system for [ 18 F]FES by modifying a cassette-type [ 18 F]fluorodeoxyglucose synthesizer. Two milligrams of 3-O-methoxymethyl-16,17-O-sulfuryl-16-epiestriol in acetonitrile was heated at 105 o C for 10 min with dried [ 18 F]fluoride. The resultant solution was evaporated and hydrolyzed with 0.2 N HCl in 90% acetonitrile/water at 95 o C for 10 min under pressurized condition. The neutralization was carried out with 2.8% NaHCO 3 , and then the high-performance liquid chromatography (HPLC) purification was performed. The desired radioactive fraction was collected and the solvent was replaced by 10 ml of saline, and then passed through a 0.22-μm filter into a pyrogen-free vial as the final product. The HPLC purification data demonstrated that [ 18 F]FES was synthesized with a yield of 76.4±1.9% (n=5). The yield as the final product for clinical use was 42.4±3.2% (n=5, decay corrected). The total preparation time was 88.2±6.4 min, including the HPLC purification and the solvent replacement process. The radiochemical purity of the final product was >99%, and the specific activity was more than 111 GBq/μmol. The final product was stable for more than 6 h in saline containing sodium ascorbate. This new preparation system enables us to produce [ 18 F]FES safe for clinical use with high and reproducible yield

Development of a sensor for L-Dopa based on Co(DMG)(2)ClPy/multi-walled carbon nanotubes composite immobilized on basal plane pyrolytic graphite electrode.

Science.gov (United States)

Leite, Fernando Roberto Figueirêdo; Maroneze, Camila Marchetti; de Oliveira, Adriano Bof; dos Santos, Wallans Torres Pio; Damos, Flavio Santos; Silva Luz, Rita de Cássia

2012-08-01

L-Dopa is the immediate precursor of the neurotransmitter dopamine, being the most widely prescribed drug in the treatment of Parkinson's disease. A sensitive and selective method is presented for the voltammetric determination of L-Dopa in pharmaceutical formulations using a basal plane pyrolytic graphite (BPPG) electrode modified with chloro(pyridine)bis(dimethylglyoximato)cobalt(III) (Co(DMG)(2)ClPy) absorbed in a multi-walled carbon nanotube (MWCNT). Scanning Electron Microscopy and Fourier Transform Infrared Spectroscopy were used to characterize the materials. The electrocatalytical oxidation of L-Dopa using the Co(DMG)(2)ClPy/MWCNT/BPPG electrode was investigated by cyclic voltammetry and square wave voltammetry. The parameters that influence the electrode response (the amount of Co(DMG)(2)ClPy and of MWCNT, buffer solution, buffer concentration, buffer pH, frequency and potential pulse amplitude) were investigated. Voltammetric peak currents showed a linear response for L-Dopa concentration in the range of 3 to 100 μM, with a sensitivity of 4.43 μAcm(-2)/μM and a detection limit of 0.86 μM. The related standard deviation for 10 determinations of 50 μM L-Dopa was 1.6%. The results obtained for L-Dopa determination in pharmaceutical formulations (tablets) were in agreement with the compared official method. The sensor was successfully applied for L-Dopa selective determination in pharmaceutical formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

A new knock-in mouse model of l-DOPA-responsive dystonia.

Science.gov (United States)

Rose, Samuel J; Yu, Xin Y; Heinzer, Ann K; Harrast, Porter; Fan, Xueliang; Raike, Robert S; Thompson, Valerie B; Pare, Jean-Francois; Weinshenker, David; Smith, Yoland; Jinnah, Hyder A; Hess, Ellen J

2015-10-01

Abnormal dopamine neurotransmission is associated with many different genetic and acquired dystonic disorders. For instance, mutations in genes critical for the synthesis of dopamine, including GCH1 and TH cause l-DOPA-responsive dystonia. Despite evidence that implicates abnormal dopamine neurotransmission in dystonia, the precise nature of the pre- and postsynaptic defects that result in dystonia are not known. To better understand these defects, we generated a knock-in mouse model of l-DOPA-responsive dystonia (DRD) mice that recapitulates the human p.381Q>K TH mutation (c.1141C>A). Mice homozygous for this mutation displayed the core features of the human disorder, including reduced TH activity, dystonia that worsened throughout the course of the active phase, and improvement in the dystonia in response to both l-DOPA and trihexyphenidyl. Although the gross anatomy of the nigrostriatal dopaminergic neurons was normal in DRD mice, the microstructure of striatal synapses was affected whereby the ratio of axo-spinous to axo-dendritic corticostriatal synaptic contacts was reduced. Microinjection of l-DOPA directly into the striatum ameliorated the dystonic movements but cerebellar microinjections of l-DOPA had no effect. Surprisingly, the striatal dopamine concentration was reduced to ∼1% of normal, a concentration more typically associated with akinesia, suggesting that (mal)adaptive postsynaptic responses may also play a role in the development of dystonia. Administration of D1- or D2-like dopamine receptor agonists to enhance dopamine signalling reduced the dystonic movements, whereas administration of D1- or D2-like dopamine receptor antagonists to further reduce dopamine signalling worsened the dystonia, suggesting that both receptors mediate the abnormal movements. Further, D1-dopamine receptors were supersensitive; adenylate cyclase activity, locomotor activity and stereotypy were exaggerated in DRD mice in response to the D1-dopamine receptor agonist SKF

Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

Energy Technology Data Exchange (ETDEWEB)

Santhanam, Prasanna; Chandramahanti, Sangeeta [Marshall University, Section of Endocrinology, Department of Internal Medicine, Joan C Edwards School of Medicine, Huntington, WV (United States); Kroiss, Alexander [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Yu, Run [Cedars-Sinai Medical Center, Division of Endocrinology and Carcinoid and Neuroendocrine Tumor Center, Los Angeles, CA (United States); Ruszniewski, Philippe [Beaujon Hospital and Paris-Diderot University, Department of Gastroenterology-Pancreatology, Paris (France); Kumar, Rakesh [All India Institute of Medical Sciences, Diagnostic Nuclear Medicine Division, Department of Nuclear Medicine, New Delhi (India); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France)

2015-03-13

Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a poor prognosis (10-year survival 22 %), grade 1 and 2 NETs having a more favorable outcome than grade 3 (also called carcinoma). There is evidence that an effort should be made to localize the primary tumor even in the presence of metastasis because resection of the primary tumor(s) may improve disease-free and overall survival, and because the choice of chemotherapeutic agent depends on the location of the primary tumor. Localization of the tumors remains challenging and often relies on a combination of radiological, endoscopic and functional imaging. The functional imaging protocol for evaluation of these patients has historically relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and specificity of SRS may be unsatisfactory, especially for NETs of midgut origin. Newer PET radiotracers such as {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSTa) and {sup 18}F-DOPA have shown promise. In direct comparisons between {sup 68}Ga-DOTA-SSTa PET/CT and {sup 99m}Tc-HYNIC-octreotide/{sup 111}In-pentetreotide SPECT(/CT), {sup 68}Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. {sup 18}F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of {sup 18}F-DOPA by the normal exocrine pancreas can be somewhat overcome by pretreatment with carbidopa. We have suggested a protocol in which SRS is replaced by one of the two agents (preferably with {sup 68}Ga-DOTA-SSTa, alternatively {sup 18}F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and {sup 18}F-FDG PET/CT may be an additional diagnostic test for poorly differentiated tumors and for prognostication. In the near future, it is expected that patients with CUP-NET will benefit from newly

Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

International Nuclear Information System (INIS)

Santhanam, Prasanna; Chandramahanti, Sangeeta; Kroiss, Alexander; Yu, Run; Ruszniewski, Philippe; Kumar, Rakesh; Taieb, David

2015-01-01

Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a poor prognosis (10-year survival 22 %), grade 1 and 2 NETs having a more favorable outcome than grade 3 (also called carcinoma). There is evidence that an effort should be made to localize the primary tumor even in the presence of metastasis because resection of the primary tumor(s) may improve disease-free and overall survival, and because the choice of chemotherapeutic agent depends on the location of the primary tumor. Localization of the tumors remains challenging and often relies on a combination of radiological, endoscopic and functional imaging. The functional imaging protocol for evaluation of these patients has historically relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and specificity of SRS may be unsatisfactory, especially for NETs of midgut origin. Newer PET radiotracers such as 68 Ga-labeled somatostatin analogs ( 68 Ga-DOTA-SSTa) and 18 F-DOPA have shown promise. In direct comparisons between 68 Ga-DOTA-SSTa PET/CT and 99m Tc-HYNIC-octreotide/ 111 In-pentetreotide SPECT(/CT), 68 Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. 18 F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of 18 F-DOPA by the normal exocrine pancreas can be somewhat overcome by pretreatment with carbidopa. We have suggested a protocol in which SRS is replaced by one of the two agents (preferably with 68 Ga-DOTA-SSTa, alternatively 18 F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and 18 F-FDG PET/CT may be an additional diagnostic test for poorly differentiated tumors and for prognostication. In the near future, it is expected that patients with CUP-NET will benefit from newly developed PET approaches (radiopharmaceuticals) and

Elevated [(18)F]FDOPA utilization in the periaqueductal gray and medial nucleus accumbens of patients with early Parkinson's disease

DEFF Research Database (Denmark)

Kumakura, Yoshitaka; Danielsen, Erik H; Gjedde, Albert

2009-01-01

, there have been several reports of focal elevations of FDOPA utilization in brain of patients with Parkinson's disease (PD), all based on reference tissue methods. To investigate this phenomenon further, we used voxel-wise steady-state kinetic analysis to search for regions of elevated FDOPA utilization (K......; ml g(-1) min(-1)) and steady-state trapping (V(d); ml g(-1)) in a group of well-characterized patients with early, asymmetric PD, who were contrasted with an age-matched control group. Subtraction of the population mean parametric maps revealed foci of increased FDOPA utilization K (+25...

Presynaptic mechanisms of L-DOPA-induced dyskinesia: the findings, the debate, the therapeutic implications.

Directory of Open Access Journals (Sweden)

M Angela eCenci

2014-12-01

Full Text Available The dopamine precursor L-DOPA has been the most effective treatment for Parkinson´s disease (PD for over 40 years. However, the response to this treatment changes during the progression of PD, and most patients develop dyskinesias (abnormal involuntary movements and motor fluctuations within a few years of L-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal dopamine transmission. Several presynaptic mechanisms converge to generate large dopamine swings in the brain concomitant with the peaks-and-troughs of plasma L-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in dopamine transmission depend on deficiency/dysfunction of the dopamine transporter, aberrant release of dopamine from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from dopamine play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of L-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

Rapid screening for cyclo-dopa and diketopiperazine alkaloids in crude extracts of Portulaca oleracea L. using liquid chromatography/tandem mass spectrometry.

Science.gov (United States)

Xing, Jie; Yang, Zijuan; Lv, Beibei; Xiang, Lan

2008-05-01

A simple and rapid qualitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for screening cyclo-dopa and diketopiperazine alkaloids in crude extracts of Portulaca oleracea L. at sub-ppm levels. An electrospray ionization orbitrap mass spectrometer, which provides accurate full scan MS and MS/MS data, was used in this study. After simple extraction with ethanol and purification by AB-8 resin, the extracts were subjected to LC/MS/MS analysis. A high mass tolerance (10 ppm) was used in the initial screening to filter the full scan MS data. The cyclo-dopa and diketopiperazine alkaloid standards gave limits of detection (LODs) at or below 5 ng/mL. The results also indicated that the method had an acceptable precision for day-to-day use in the identification of compounds. The alkaloids could be identified based on their MS/MS data, elemental compositions, and retention behavior. This system was used to assay trace amounts of cyclo-dopa and diketopiperazine alkaloids in crude extracts of Portulaca oleracea L., leading to the identification of 5/2 confirmed/unconfirmed cyclo-dopa and 7/6 confirmed/unconfirmed diketopiperazine alkaloids, respectively. The screening method considerably reduces the time and cost involved in the identification of cyclo-dopa and diketopiperazine alkaloids in Portulaca oleracea L., as well as being a simple and convenient approach to the identification of other structural families of natural products. Copyright (c) 2008 John Wiley & Sons, Ltd.

Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

Science.gov (United States)

Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

2011-01-01

Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

Physical Exercise Modulates L-DOPA-Regulated Molecular Pathways in the MPTP Mouse Model of Parkinson's Disease.

Science.gov (United States)

Klemann, Cornelius J H M; Xicoy, Helena; Poelmans, Geert; Bloem, Bas R; Martens, Gerard J M; Visser, Jasper E

2018-07-01

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas. MPTP reduced the number of DA neurons in the SNpc, whereas physical exercise improved beam walking, rotarod performance, and motor behavior in the open field. Further, enrichment analyses of the RNA-sequencing data revealed that in the MPTP-treated mice physical exercise predominantly modulated signaling cascades that are regulated by the top upstream regulators L-DOPA, RICTOR, CREB1, or bicuculline/dalfampridine, associated with movement disorders, mitochondrial dysfunction, and epilepsy-related processes. To elucidate the molecular pathways underlying these cascades, we integrated the proteins encoded by the exercise-induced differentially expressed mRNAs for each of the upstream regulators into a molecular landscape, for multiple key brain areas. Most notable was the opposite effect of physical exercise compared to previously reported effects of L-DOPA on the expression of mRNAs in the SN and the ventromedial striatum that are involved in-among other processes-circadian rhythm and signaling involving DA, neuropeptides, and endocannabinoids. Altogether, our findings suggest that physical exercise can improve motor function in PD and may, at the same time, counteract L-DOPA-mediated molecular mechanisms. Further, we hypothesize that physical exercise has the potential to improve non-motor symptoms of PD, some of which may be the result of (chronic) L-DOPA use.

Tratamento do parkinsonismo com L-Dopa

Directory of Open Access Journals (Sweden)

Nilton Luís Latuf

1972-06-01

Full Text Available São apresentados os resultados obtidos no tratamento de 54 pacientes parkinsonianos com L-Dopa. A intensidade dos sintomas foi avaliada mediante a escala NUDS (Northwestern University Disability Scales antes e após o tratamento. Os autores ressaltam a obtenção de melhores resultados no que respeita à rigidez e à discinesia, em comparação com o tremor. São apontados os efeitos colaterais, quase sempre de pequena intensidade e corrigíveis com a diminuição ou suspensão da administração medicamentosa.

The effect of L-dopa in Parkinson's disease as revealed by neurophysiological studies of motor and sensory functions.

Science.gov (United States)

Suppa, Antonio; Bologna, Matteo; Conte, Antonella; Berardelli, Alfredo; Fabbrini, Giovanni

2017-02-01

This review will first discuss evidence of motor and sensory abnormalities as yielded by neurophysiological techniques in patients with PD. It will then go on to describe the effects of L-dopa replacement on motor and sensory abnormalities in PD as assessed by neurophysiological studies. Areas covered: We analyzed papers in English using Pubmed with the following keywords: L-dopa, dopamine, bradykinesia, basal ganglia, kinematic analysis, TMS, motor cortex plasticity, motor cortex excitability, somatosensory discrimination threshold, pain Expert commentary: L-dopa improves the amplitude and speed of upper limb voluntary movements, but it does not restore abnormalities in the sequence effect or voluntary facial movements. L-dopa only partially normalizes changes in motor cortex excitability and plasticity and has also contrasting effects on the sensory system and on sensory-motor integration. The neurophysiological studies reviewed here show that PD is more than a hypo-dopaminergic disease, and non-dopaminergic mechanisms should also be considered.

Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease

NARCIS (Netherlands)

Antonini, A; Leenders, KL; Vontobel, P; Maguire, RP; Missimer, J; Psylla, M; Gunther, [No Value

1997-01-01

We used PET with the tracers [F-18]fluorodeoxyglucose (FDG), [F-18]fluorodopa (FDOPA) and [C-11]raclopride (RACLO) to study striatal glucose and dopa metabolism, and dopamine D-2 receptor binding, respectively, in nine patients with multiple system atrophy. Ten patients with classical Parkinson's

The improved syntheses of 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) using a multistep one-pot strategy

International Nuclear Information System (INIS)

Cai Hancheng; Li Zibo; Conti, Peter S.

2011-01-01

Introduction: We and others have previously reported a four-step radiosynthesis of a series of 2'-deoxy-2'-[ 18 F]fluoro-5-substituted-1-β-D-arabinofuranosyluracil derivatives including [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU as thymidine derivatives for tumor proliferation and/or reporter gene expression imaging with positron emission tomography (PET). Although the radiosynthesis has been proven to be reproducible and efficient, this complicated multistep reaction is difficult to incorporate into an automated cGMP-compliant radiosynthesis module for routine production. Recently, we have developed a simple and efficient one-pot method for routine production of [ 18 F]FMAU. In this study, we studied the feasibility of radiosynthesizing [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU using this newly developed method. Methods: Similar to the radiosynthesis of [ 18 F]FMAU, 5-substituted 2'-[ 18 F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU) were synthesized in one-pot radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS. Results: This one-pot radiosynthesis method could be used to produce [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU. The overall radiochemical yields of these tracers varied from 4.1%±0.8% to 10.1%±1.9% (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150 min from the end of bombardment, and the radiochemical purity was >99%. Conclusions: The improved radiosyntheses of [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU have been achieved with reasonable yields and high purity using a multistep one-pot method. The synthetic time has been reduced, and the reaction procedures have been significantly simplified. The success of this approach may make PET tracers [ 18 F]FAU, [ 18 F

Interaction of Human Dopa Decarboxylase with L-Dopa: Spectroscopic and Kinetic Studies as a Function of pH

Directory of Open Access Journals (Sweden)

Riccardo Montioli

2013-01-01

Full Text Available Human Dopa decarboxylase (hDDC, a pyridoxal 5′-phosphate (PLP enzyme, displays maxima at 420 and 335 nm and emits fluorescence at 384 and 504 nm upon excitation at 335 nm and at 504 nm when excited at 420 nm. Absorbance and fluorescence titrations of hDDC-bound coenzyme identify a single pKspec of ~7.2. This pKspec could not represent the ionization of a functional group on the Schiff base but that of an enzymic residue governing the equilibrium between the low- and the high-pH forms of the internal aldimine. During the reaction of hDDC with L-Dopa, monitored by stopped-flow spectrophotometry, a 420 nm band attributed to the 4′-N-protonated external aldimine first appears, and its decrease parallels the emergence of a 390 nm peak, assigned to the 4′-N-unprotonated external aldimine. The pH profile of the spectral change at 390 nm displays a pK of 6.4, a value similar to that (~6.3 observed in both kcat and kcat/Km profiles. This suggests that this pK represents the ESH+ → ES catalytic step. The assignment of the pKs of 7.9 and 8.3 observed on the basic side of kcat and the PLP binding affinity profiles, respectively, is also analyzed and discussed.

Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications.

Science.gov (United States)

Cenci, M Angela

2014-01-01

The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. However, the response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal DA transmission. Several presynaptic mechanisms converge to generate large DA swings in the brain concomitant with the peaks-and-troughs of plasma l-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in DA transmission depend on deficiency/dysfunction of the DA transporter, aberrant release of DA from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from DA) play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of l-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

Effects of (-)-sesamin on motor and memory deficits in an MPTP-lesioned mouse model of Parkinson's disease treated with l-DOPA.

Science.gov (United States)

Zhao, T T; Shin, K S; Kim, K S; Park, H J; Kim, H J; Lee, K E; Lee, M K

2016-12-17

The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg). Both (-)-sesamin doses reduced decreases in the retention latency time in the passive avoidance test, latency to fall of rotarod test and distance traveled in the open field test, and attenuated decreases in tyrosine hydroxylase (TH)-immunopositive cells, dopamine, and its metabolites in the substantia nigra-striatum. (-)-Sesamin reduced increases in the retention transfer latency time in the elevated plus-maze test and N-methyl-d-aspartate receptor (NMDAR) expression and reduced decreases in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus. In contrast, daily treatment with 10mg/kg l-DOPA for 21days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50mg/kg). These results suggest that (-)-sesamin protects against habit learning memory deficits by activating the dopamine neuronal system, while spatial memory deficits are decreased by its modulatory effects on the NMDAR-ERK1/2-CREB system. Accordingly, (-)-sesamin may act as an adjuvant phytonutrient for motor and memory deficits in patients with PD receiving l-DOPA. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy

DEFF Research Database (Denmark)

Andersen, Preben B.; Krabbe, Katja; Leffers, Anne M.

2003-01-01

a median recurrence free survival of 16 years by MRI and Positron Emission Tomography using the glucose analog 2-18F-fluoro-2-deoxy-D-glucose (18FDG). Three patients were not analyzed further due to diffuse cerebral atrophy, which might be related to previous hydrocephalus. Twenty-one patients were...

A Role for Mitogen- and Stress-Activated Kinase 1 in L-DOPA-Induced Dyskinesia and ∆FosB Expression

DEFF Research Database (Denmark)

Feyder, Michael; Södersten, Erik; Santini, Emanuela

2014-01-01

BACKGROUND: Abnormal regulation of extracellular signal-regulated kinases 1 and 2 has been implicated in 3,4-dihydroxy-l-phenylalanine (L-DOPA)-induced dyskinesia (LID), a motor complication affecting Parkinson's disease patients subjected to standard pharmacotherapy. We examined the involvement...... of mitogen- and stress-activated kinase 1 (MSK1), a downstream target of extracellular signal-regulated kinases 1 and 2, and an important regulator of transcription in LID. METHODS: 6-Hydroxydopamine was used to produce a model of Parkinson's disease in MSK1 knockout mice and in ∆FosB- or ∆c......Jun-overexpressing transgenic mice, which were assessed for LID following long-term L-DOPA administration. Biochemical processes were evaluated by Western blotting or immunofluorescence. Histone H3 phosphorylation was analyzed by chromatin immunoprecipitation followed by promotor-specific quantitative polymerase chain reaction...

Synthesis of O-[2-[18F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propyl]tyrosine ([18F]FNT]) as a new class of tracer for imaging hypoxia

International Nuclear Information System (INIS)

Noeen Malik; Xian Lin; Christoph Solbach; Hans-Juergen Machulla; Bin Shen; Gerald Reischl; Wolfgang Voelter

2012-01-01

For detection of hypoxic tumor tissue, all radiotracers synthesized until now, are based on the concept that cellular uptake is being controlled by diffusion. As a new approach, we chose the concept to have the tracer hypothetically transported into the cells by well known carrier systems like the amino acid transporters. For this purpose, radiosynthesis of O-[2-[ 18 F]fluoro-3-(2-nitro-1H-imidazole-1yl)propyl]tyrosine ([18F]FNT]) was carried out from methyl 2-(benzyloxycarbonyl)-3-(4-3-(2-nitro-1H-imidazol-1-yl) -2-(tosyloxy)propoxy) phenyl)propanoate via no-carrier-added nucleophilic aliphatic substitution. After labelling, 81 ± 0.9% of labelled intermediate i.e. methyl 2-(benzyloxycarbonyl)-3-(4-(2-[ 18 F]fluoro-3- (2-nitro-1H-imidazole-1-yl)propoxy) phenyl)propanoate was obtained at 140 deg C. At the end of radiosynthesis, [ 18 F]FNT was obtained in an overall radiochemical yield of 40 ± 0.9% (not decay corrected) within 90 min in a radiochemical purity of >98% in a formulation ready for application in the clinical studies for PET imaging of hypoxia. (author)

Parkinson disease and positron tomography

International Nuclear Information System (INIS)

Baron, J.C.

1984-10-01

Physiopathologic investigations of Parkinson disease and parkinsonian syndrome using positron tomography are briefly reviewed: study of cerebral blood flow and metabolism; effects of L-DOPA; study of dopaminergic receptors and of 18 F-Fluoro-L-DOPA incorporation [fr

Radioenzymatic assay of DOPA (3,4-dihydroxyphenylalanine)

International Nuclear Information System (INIS)

Johnson, G.A.; Gren, J.M.; Kupiecki, R.

1978-01-01

We modified the single-isotope radioenzymatic assay for catecholamines [Life Sci. 21, 625(1977)] to assay 3,4-dihydroxyphenylalanine (DOPA). DOPA decarboxylase is used to convert DOPA to dopamine, which concurrently is converted to [ 3 H]-3-O-methyldopamine in the presence of catechol-O-methyltransferase and [methyl- 3 H]-S-adenosylmethionine and assayed radioenzymatically. For assay of plasma DOPA, 50 μl of untreated plasma is added directly into the incubation mixture. A duplicate mixture containing an internal standard requires a second 50-μl aliquot of plasma. Because the assay measures both DOPA and endogenous dopamine, two additional aliquots of plasma must be assayed for dopamine in the absence of the decarboxylase by the differential assay; DOPA is estimated by difference. The assay is sensitive to 25 pg (500 ng/liter of plasma). Analysis of DOPA (DOPA plus dopamine) and the concurrent differential assay of catecholamines in at least 10 samples can be done in a single working day. Plasma DOPA concentrations for 42 normotensive adults were 1430 +- 19 ng/liter (mean +- SEM). In contrast, dopamine concentrations for these same subjects averaged 23 +- 20 ng/liter. Values for the 24 women subjects (1510 +- 62 ng/liter) significantly (P = 0.04) exceeded those for the men

Synthesis procedure for routine production of 2-[{sup 18}F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[{sup 18}F]F-A-85380)

Energy Technology Data Exchange (ETDEWEB)

Schildan, Andreas [Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig (Germany)], E-mail: andreas.schildan@medizin.uni-leipzig.de; Patt, Marianne; Sabri, Osama [Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig (Germany)

2007-11-15

2-[{sup 18}F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[{sup 18}F]F-A-85380) was among the first subtype selective radioligands to visualise the in vivo distribution of {alpha}4{beta}2-containing neuronal nicotinic acetylcholine receptors (nAChRs) in human brain. We developed a one-pot synthesis for the preparation of 2-[{sup 18}F]F-A-85380 in a commercially available TRACERlab FX{sub F-N} synthesis module. The synthesis comprises a nucleophilic substitution followed by hydrolysis of a t-butyloxycarbonyl (BOC)-protected intermediate. After formulation for intravenous application up to 20 GBq 2-[{sup 18}F]F-A-85380 were produced from a starting activity of 100 GBq [{sup 18}F]fluoride in 60 min with a specific activity of about 4.10{sup 5} GBq/mmol and a mean radiochemical purity of more than 99%.

Gynostemma pentaphyllum Ethanolic Extract Protects Against Memory Deficits in an MPTP-Lesioned Mouse Model of Parkinson's Disease Treated with L-DOPA.

Science.gov (United States)

Kim, Kyung Sook; Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Cho, Yoon Jeong; Lee, Kyung Eun; Kim, Seung Hwan; Lee, Myung Koo

2017-01-01

This study investigated the effects of ethanol extract from Gynostemma pentaphyllum (GP-EX) on memory deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) (MPTP-lesioned mice). MPTP (30 mg/kg/day, 5 days)-lesioned mice showed deficits of habit learning memory and spatial memory, which were further aggravated by treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) (25 mg/kg, 21 days). However, treatment with GP-EX (50 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice treated with L-DOPA (25 mg/kg): GP-EX prevented the decreases in retention latency time in the passive avoidance test and tyrosine hydroxylase-immunopositive cells and dopamine levels in the nigrostriatum. GP-EX also reduced increases in retention transfer latency time of the elevated plus-maze test and expression of N-methyl-D-aspartate (NMDA) receptor and improved decreases in phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus in the same models. By contrast, L-DOPA treatment (10 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice, which were further improved by GP-EX treatment. These results suggest that GP-EX ameliorates habit learning memory deficits by activating dopaminergic neurons and spatial memory deficits by modulating NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mice treated with L-DOPA. GP-EX may serve as an adjuvant phytonutrient for memory deficits in PD.

L-Dopa decarboxylase expression profile in human cancer cells.

Science.gov (United States)

Chalatsa, Ioanna; Nikolouzou, Eleftheria; Fragoulis, Emmanuel G; Vassilacopoulou, Dido

2011-02-01

L-Dopa decarboxylase (DDC) catalyses the decarboxylation of L-Dopa. It has been shown that the DDC gene undergoes alternative splicing within its 5'-untranslated region (UTR), in a tissue-specific manner, generating identical protein products. The employment of two alternative 5'UTRs is thought to be responsible for tissue-specific expression of the human DDC mRNA. In this study, we focused on the investigation of the nature of the mRNA expression in human cell lines of neural and non-neural origin. Our results show the expression of a neural-type DDC mRNA splice variant, lacking exon 3 in all cell lines studied. Co-expression of the full length non-neural DDC mRNA and the neural-type DDC splice variant lacking exon 3 was detected in all cell lines. The alternative DDC protein isoform, Alt-DDC, was detected in SH-SY5Y and HeLa cells. Our findings suggest that the human DDC gene undergoes complex processing, leading to the formation of multiple mRNA isoforms. The study of the significance of this phenomenon of multiple DDC mRNA isoforms could provide us with new information leading to the elucidation of the complex biological pathways that the human enzyme is involved in.

Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson's Disease

Institute of Scientific and Technical Information of China (English)

Si-Yue Li; Ya-Li Wang; Wen-Wen Liu; Dong-Jun Lyu; Fen Wang; Cheng-Jie Mao; Ya-Ping Yang; Li-Fang Hu; Chun-Feng Liu

2017-01-01

Background:Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction.However,it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself,or is affected by L-DOPA replacement therapy.This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD.Methods:The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA),followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days.Rotarod test,footprint test,and open-field test were carried out to evaluate the motor function.Striatum,suprachiasmatic nucleus (SCN),liver,and plasma were collected at 6:00,12:00,18:00,and 24:00.Quantitative real-time polymerase chain reaction was used to examine the expression of clock genes.Enzyme-linked immunosorbent assay was used to determine the secretion level of cortisol and melatonin.High-performance liquid chromatography was used to measure the neurotransmitters.Analysis of variance was used for data analysis.Results:L-DOPA alleviated the motor deficits induced by 6-OHDA lesions in the footprint and open-field test (P ＜ 0.01,P ＜ 0.001,respectively).After L-DOPA treatment,Bmal1 decreased in the SCN compared with 6-OHDA group at 12:00 (P ＜ 0.01) and 24:00 (P ＜ 0.001).In the striatum,the expression ofBmal1,Rorα was lower than that in the 6-OHDA group at 18:00 (P ＜ 0.05) and L-DOPA seemed to delay the peak of Per2 to 24:00.In liver,L-DOPA did not affect the rhythmicity and expression of these clock genes (P ＞ 0.05).In addition,the cortisol secretion was increased (P ＞ 0.05),but melatonin was further inhibited after L-DOPA treatment at 6:00 (P ＜ 0.01).Conclusions:In the circadian system of advanced PD rat models,circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further aggravate it.

Radiosynthesis of 1-[{sup 18}F]fluoroethyl-L-tryptophan as a novel potential amino acid PET tracer

Energy Technology Data Exchange (ETDEWEB)

Sun Ting, E-mail: beibeisun2008@163.com [Department of Cardiac Function, Shanghai Ninth People' s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Tang Ganghua, E-mail: gtang0224@yahoo.com.cn [Department of Nuclear Medicine, the first affiliated hospital, SunYat-Sen University, Guangzhou 510080 (China); Tian Hua [State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032 (China); Wang Xiaoyan [Department of Nuclear Medicine, the first affiliated hospital, SunYat-Sen University, Guangzhou 510080 (China); Chen Xianghua [Department of Cardiac Function, Shanghai Ninth People' s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Chen Zhifeng [Department of Nuclear Medicine, the first affiliated hospital, SunYat-Sen University, Guangzhou 510080 (China); Wang Shihchen [Department of Nuclear Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, 1 Shuaifuyuan Wangfujing Beijing 100730 (China)

2012-04-15

{sup 18}F labeled natural amino acids have been introduced as promising tumor imaging agents. A novel [{sup 18}F]fluoro amino acid analog 1-[{sup 18}F]fluoroethyl-L-tryptophan (1-[{sup 18}F]FETrp) was designed and synthesized by a two-pot three-step procedure, including the synthesis of 1-[{sup 18}F]fluoro-2- (tosyloxy)ethane, the [{sup 18}F]fluoroethylation of the precursor N-Boc-L-tryptophan ethyl ester and following the deprotection of the tert-butoxycarbonyl and ethyl ester protecting groups. 1-[{sup 18}F]FETrp was resulted in 0.9{+-}0.2% (n=5) radiochemical yields (no decay corrected) by HPLC purification, within a total synthesis time of 65 min. The radiochemical purity of 1-[{sup 18}F]FETrp was 95-97%. The radiosynthetic method needs to be further optimized to get a satisfying radiochemical yield. - Highlights: Black-Right-Pointing-Pointer We designed and synthesized the novel amino acid analog 1-[{sup 19}F]FETrp. Black-Right-Pointing-Pointer We radiosynthesized 1-[{sup 18}F]FETrp using the two-pot three-step procedure. Black-Right-Pointing-Pointer The total synthesis time was 65 min and the yield was very low. Black-Right-Pointing-Pointer The synthetic strategy via [{sup 18}F]FCH{sub 2}CH{sub 2}OTs needs to be optimized or changed.

Synthesis of 2-[18F]fluoro-L-tyrosine via regiospecific fluoro-de-stannylation

International Nuclear Information System (INIS)

Hess, E.; Sichler, S.; Kluge, A.; Coenen, H.H.

2002-01-01

2-[ 18 F]Fluoro-L-tyrosine is a fluorine labelled amino acid, known to be incorporated into newly synthesised proteins, rendering it a potentially suitable tracer to image protein metabolism in vivo using positron emission tomography. For the electrophilic preparation of 2-[ 18 F]fluoro-L-tyrosine three protected 2-trialkylstannyl tyrosine derivatives have been synthesised for the first time as precursors. While O,N-di-Boc-2-triethylstannyl-L-tyrosine ethylester has proved to be suitable as precursor for radiosynthesis, imidazolidinon-derivatives of 2-triaklylstannyl tyrosine have not because of difficult fast hydrolysis of a phenolic O-methyl protective group. The di-Boc-tin derivative of tyrosine ethylester readily reacted with [ 18 F]F 2 , which was prepared via the 18 O(p,n) 18 F nuclear reaction. 2-[ 18 F]Fluoro-L-tyrosine was isolated after full deprotection with aqueous hydrobromic acid and HPLC purification with activities of 1.41±0.32 GBq. The isomeric and enantiomeric purity is high (both >99%). The preparation procedure is facile and easy to automate. The chemical yields of this fluoro-de-stannylation reaction as well as of the synthesis of 6-[ 18 F]fluoro-L-dopa, determined with an analogous precursor and non-radioactive fluorine under identical conditions, amounted to 42.7±1.6% and 60.2±2.8%, respectively

Radiosynthesis of F-18 labeled cytidine analog 2'-fluoro-5-iodo-l-β-D-arabinofuranosylcytosine ([18F]FIAC)

International Nuclear Information System (INIS)

Wu, C.-Y.; Chan, P.-C.; Chang, W.-T.; Liu, R.-S.; Alauddin, Mian M.; Wang, H-E.

2009-01-01

We reported the synthesis of 2'-deoxy-2'-[ 18 F]fluoro-5-iodo-1-β-D-arabinofuranosyl-5-iodo-cytosine ([ 18 F]FIAC) with 15-20% radiochemical yield (decay corrected) in 3.5 h. 2-deoxy-2-[ 18 F]fluoro-1,3,5-tri-O-benzoyl-α-D-arabinofuranose was prepared following literature procedures with some modifications (yield>70%). The 18 F-fluorosugar was converted to 1-bromo- 18 F-fluorosugar, and then coupled with 5-iodocytocine silyl ether. A mixture of acetonitrile (ACN) and 1,2-dichloroethane (DCE) were employed to achieve optimum radiochemical yield and acceptable β-anomer selectivity (α/β=1/3). After hydrolyzed with sodium methoxide, the crude product was purified using HPLC to afford the β-[ 18 F]FIAC with high radiochemical purity (≥98%).

L-DOPA concentration variation in the leaf and flower tissues of six faba bean lines with common and rare flower colors

Science.gov (United States)

Faba bean is one of the a few plant species that can produce the medicinally important molecule, L-3,4-dihydroxy phenylalanine (L-DOPA), the major ingredient of several prescription drugs used to treat Parkinson’s disease. L-DOPA can cross the blood-brain barrier, where it is converted to dopamine, ...

Enhanced permeability and antifouling performance of cellulose acetate ultrafiltration membrane assisted by l-DOPA functionalized halloysite nanotubes.

Science.gov (United States)

Mu, Keguang; Zhang, Dalun; Shao, Ziqiang; Qin, Dujian; Wang, Yalong; Wang, Shuo

2017-10-15

l-Dopa functionalized halloysite nanotubes (HNTs) were prepared by the self-polymerization of l-dopa in the weak alkaline condition. Then different contents of l-dopa coated HNTs (LPDHNTs) were blended into cellulose acetate to prepare enhanced performance ultrafiltration membranes via the phase inversion method. The HNTs and LPDHNTs were characterized by FTIR, XPS, and TEM anysis. And the membranes morphologies, separation performance, antifouling performance, mechanical properties and hydrophilicity were also investigated. It was found that the composite membranes exhibited excellent antifouling performance. The pure water flux of 3.0wt% LPDHNTs/CA membrane increased from 11.4Lm -2 h -1 to 92.9Lm -2 h -1 , while the EA rejection ratio of the membrane was about 91.2%. In addition, the mechanical properties of the resultant membranes were strengthened compared with the CA ultrafiltration membrane. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of Serotonin Neurons in L-DOPA- and Graft-Induced Dyskinesia in a Rat Model of Parkinson's Disease

Directory of Open Access Journals (Sweden)

Eunju Shin

2012-01-01

Full Text Available L-DOPA, the most effective drug to treat motor symptoms of Parkinson's disease, causes abnormal involuntary movements, limiting its use in advanced stages of the disease. An increasing body of evidence points to the serotonin system as a key player in the appearance of L-DOPA-induced dyskinesia (LID. In fact, exogenously administered L-DOPA can be taken up by serotonin neurons, converted to dopamine and released as a false transmitter, contributing to pulsatile stimulation of striatal dopamine receptors. Accordingly, destruction of serotonin fibers or silencing serotonin neurons by serotonin agonists could counteract LID in animal models. Recent clinical work has also shown that serotonin neurons are present in the caudate/putamen of patients grafted with embryonic ventral mesencephalic cells, producing intense serotonin hyperinnervation. These patients experience graft-induced dyskinesia (GID, a type of dyskinesia phenotypically similar to the one induced by L-DOPA but independent from its administration. Interestingly, the 5-HT1A receptor agonist buspirone has been shown to suppress GID in these patients, suggesting that serotonin neurons might be involved in the etiology of GID as for LID. In this paper we will discuss the experimental and clinical evidence supporting the involvement of the serotonin system in both LID and GID.

6-[18F]fluoro-A-85380: an in vivo tracer for the nicotinic acetylcholine receptor

International Nuclear Information System (INIS)

Scheffel, Ursula; Horti, Andrew G.; Koren, Andrei O.; Ravert, Hayden T.; Banta, Jeffrey P.; Finley, Paige A.; London, Edythe D.; Dannals, Robert F.

2000-01-01

6-[ 18 F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[ 18 F]fluoro-A-85380 or 6-[ 18 F]FA), a new tracer for positron emission tomography, was synthesized by no-carrier-added [ 18 F] fluorination of 6-iodo-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)methoxy)pyridine followed by acidic deprotection. 6-[ 18 F]FA followed the regional densities of brain nicotinic acetylcholine receptors (nAChRs) reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 6-FA. A preliminary toxicology study of the 6-FA showed a relatively low biological effect

Development of a microchip-pulsed electrochemical method for rapid determination of L-DOPA and tyrosine in Mucuna pruriens.

Science.gov (United States)

Li, Xinchun; Chen, Zuanguang; Yang, Fan; Pan, Jianbin; Li, Yinbao

2013-05-01

L-3,4-dihydroxyphenylalanine (L-DOPA) is a well-recognized therapeutic compound to Parkinson's disease. Tyrosine is a precursor for the biosynthesis of L-DOPA, both of which are widely found in traditional medicinal material, Mucuna pruriens. In this paper, we described a validated novel analytical method based on microchip capillary electrophoresis with pulsed electrochemical detection for the simultaneous measurement of L-DOPA and tyrosine in M. pruriens. This protocol adopted end-channel amperometric detection using platinum disk electrode on a homemade glass/polydimethylsiloxane electrophoresis microchip. The background buffer consisted of 10 mM borate (pH 9.5) and 0.02 mM cetyltrimethylammonium bromide, which can produce an effective resolution for the two analytes. In the optimal condition, sufficient electrophoretic separation and sensitive detection for the target analytes can be realized within 60 s. Both tyrosine and L-DOPA yielded linear response in the concentration range of 5.0-400 μM (R(2) > 0.99), and the LOD were 0.79 and 1.1 μM, respectively. The accuracy and precision of the established method were favorable. The present method shows several merits such as facile apparatus, high speed, low cost and minimal pollution, and provides a means for the pharmacologically active ingredients assay in M. pruriens. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oxidation of DNA, proteins and lipids by DOPA, protein-bound DOPA, and related catechol(amine)s

DEFF Research Database (Denmark)

Pattison, David I; Dean, Roger T; Davies, Michael Jonathan

2002-01-01

Incubation of free 3,4-dihydroxyphenylalanine (DOPA), protein-bound DOPA (PB-DOPA) and related catechols with DNA, proteins and lipids has been shown to result in oxidative damage to the target molecule. This article reviews these reactions with particular emphasis on those that occur in the pres......Incubation of free 3,4-dihydroxyphenylalanine (DOPA), protein-bound DOPA (PB-DOPA) and related catechols with DNA, proteins and lipids has been shown to result in oxidative damage to the target molecule. This article reviews these reactions with particular emphasis on those that occur...... in the presence of molecular O(2) and redox-active metal ions (e.g. Fe(3+), Cu(2+), Cr(6+)), which are known to increase the rate of DOPA oxidation. The majority of oxidative damage appears to be mediated by reactive oxygen species (ROS) such as superoxide and HO(.) radicals, though other DOPA oxidation products...

Radiation dosimetry of 2 [18F]fluoro-2-deoxy-D-glucose in man

International Nuclear Information System (INIS)

Jones, S.C.; Alavi, A.; Christman, D.; Montanez, I.; Wolf, A.P.; Reivich, M.

1982-01-01

Bladder and brain time-activity measurements in humans were performed after the intravenous administration of 2-[ 18 F]fluoro-2-deoxy-D-glucose. Radiation doses were calculated using the MIRD schema. The bladder wall received an average of 440 mrad/mCi (s.e. 76) in ten subjects who voided at 2 hr after administration of tracer. If these subjects had voided at 1 hr, the bladder-wall dose would have been reduced to 220 mrad/mCi. The brain received an average of 81 mrad/mCi in eight subjects. The doses to other organs, calculated from published dog biodistribution data, are between 50 and 85 mrad/mCi except for spleen and heart, which both received 160 mrad/mCi. These time-activity measurements for the critical organ in the human avoid the assumptions made in using animal biodistribution data for human dosimetry calculations

Synthesis of 6-[18F] and 4-[18F]fluoro-L-m-tyrosines via regioselective radiofluorodestannylation

International Nuclear Information System (INIS)

Namavari, Mohammad; Satyamurthy, N.; Phelps, M.E.; Barrio, J.R.; California Univ., Los Angeles, CA

1993-01-01

The regioselective radiofluorodestannylation of 6-trimethylstannyl-L-m-tyrosine derivative with [ 18 F]F 2 and [ 18 F]acetyl hypofluorite afforded, after acid hydrolysis, 6-[ 18 F]fluoro-L-m-tyrosine in radiochemical yields of 23 and 17%, respectively. Similarly, 4-[ 18 F]fluoro-L-m-tyrosine was synthesized in 11% radiochemical yield from the corresponding 4-trimethylstannyl-L-m-tyrosine derivative using [ 18 F]F 2 . The structural analyses of precursors, intermediates, and the final products (after 18 F decay), were carried out by 1 H, 13 C, 19 F, 119 Sn-NMR and high resolution mass spectroscopy. (author)

The influence of L-DOPA on the accumulation of lipid peroxidation products in some brain structures affected by radiation

International Nuclear Information System (INIS)

Babaev, R.A.; Kocharli, R.Kh.; Akhmedova, G.Sh.; Gasanova, A.A.; Babaev, Kh.F.

1990-01-01

A study was made of the effect of L-DOPA on the dynamics of changes in lipid peroxidation products (LPP) and the content of various types of SH-groups in certain brain structures (oblongata, cerebellum, visual and sensorimotor cortex) and their synaptosomal fractions upon irradiation. The preadministration of L-DOPA to irradiated rats inhibited LPP accumulation, prevented the decrease in the content of various types of thiols and thus exerted an antioxidant effect

Molecular imaging and the neuropathologies of Parkinson's disease

DEFF Research Database (Denmark)

Cumming, Paul; Borghammer, Per

2012-01-01

The main motor symptoms of Parkinson's disease (PD) are linked to degeneration of the nigrostriatal dopamine (DA) fibers, especially those innervating the putamen. This degeneration can be assessed in molecular imaging studies with presynaptic tracers such as [(18)F]-fluoro-L-DOPA (FDOPA...... with denervation upregulation, but there is an accelerated rate of DA receptor loss as the disease advances. Animal studies and post mortem investigations reveal changes in brain opioid peptide systems, but these are poorly documented in imaging studies of PD. Relatively minor changes in the binding sites for GABA...

Radiosynthesis of F-18 labeled cytidine analog 2'-fluoro-5-iodo-l-{beta}-D-arabinofuranosylcytosine ([{sup 18}F]FIAC)

Energy Technology Data Exchange (ETDEWEB)

Wu, C.-Y.; Chan, P.-C.; Chang, W.-T. [Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 155, Li-Nong Street, Sector 2, Bei-tou, Taipei 112, Taiwan (China); Liu, R.-S. [Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taiwan (China); Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taiwan (China); Alauddin, Mian M. [Department of Experimental Diagnostic Imagiing, MD Anderson Cancer Center, University of Texas (United States); Wang, H-E. [Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 155, Li-Nong Street, Sector 2, Bei-tou, Taipei 112, Taiwan (China)], E-mail: hewang@ym.edu.tw

2009-07-15

We reported the synthesis of 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyl-5-iodo-cytosine ([{sup 18}F]FIAC) with 15-20% radiochemical yield (decay corrected) in 3.5 h. 2-deoxy-2-[{sup 18}F]fluoro-1,3,5-tri-O-benzoyl-{alpha}-D-arabinofuranose was prepared following literature procedures with some modifications (yield>70%). The {sup 18}F-fluorosugar was converted to 1-bromo-{sup 18}F-fluorosugar, and then coupled with 5-iodocytocine silyl ether. A mixture of acetonitrile (ACN) and 1,2-dichloroethane (DCE) were employed to achieve optimum radiochemical yield and acceptable {beta}-anomer selectivity ({alpha}/{beta}=1/3). After hydrolyzed with sodium methoxide, the crude product was purified using HPLC to afford the {beta}-[{sup 18}F]FIAC with high radiochemical purity ({>=}98%)

Dynamic 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography of liver tumours without blood sampling

DEFF Research Database (Denmark)

Keiding, S; Munk, O L; Schiøtt, K M

2000-01-01

Positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is a useful diagnostic tool for the detection of tumours. Using dynamic FDG PET, net metabolic clearance of FDG, K, can be calculated by Gjedde-Patlak analysis of the time course of the radioactivity concentrations...... in tissue and arterial blood. We examined whether time-activity curves (TACs) based on arterial blood sampling could be replaced by TACs obtained from the descending aorta in dynamic PET scans of patients with liver tumours. The study was performed in two parts, using data from dynamic liver scans......, and 2.1-8.4:1 (mean, 4.6:1) based on blood sample TACs (P>0.3). We conclude that arterial blood sampling can be replaced by the present AORTA-VOI in the calculation of the net metabolic clearance of FDG in dynamic PET studies of liver tumours in human subjects. Udgivelsesdato: 2000-Apr...

Microwave-assisted one-pot radiosynthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([18F]-FMAU)

International Nuclear Information System (INIS)

Chen, Kai; Li Zibo; Conti, Peter S.

2012-01-01

Objectives: [ 18 F]-FMAU is a PET tracer being evaluated for imaging cell proliferation. Current multi-step procedures of [ 18 F]-FMAU synthesis are time-consuming, resulting in low radiochemical yield and inconvenient applications for the clinic. We have previously reported the use of Friedel-Crafts catalysts for an improved synthesis of [ 18 F]-FMAU. In this study, we investigated the efficiency of microwave-assisted radiosynthesis of [ 18 F]-FMAU in comparison with conventional thermal conditions. Methods: A simplified one-pot synthesis of [ 18 F]-FMAU was developed under microwave conditions. Various reaction times, temperatures, and microwave powers were systematically explored to optimize the coupling reaction of 2-deoxy-2-[ 18 F]fluoro-1,3,5-tri-O-benzoyl-D-arabinofuranose ([ 18 F]-sugar) and bis-2,4-(trimethylsilyloxy)-5-methyluracil (silylated uracil) in the presence of a Friedel-Crafts catalyst, trimethylsilyl trifluoromethanesulfonate (TMSOTf). Results: Microwave significantly enhanced the coupling efficiency of [ 18 F]-sugar and silylated uracil by reducing the reaction time to 10 min (6-fold reduction as compared to conventional heating) at 95 °C. Base hydrolysis followed by high-performance liquid chromatography purification produced the desired [ 18 F]-FMAU. The overall radiochemical yield was 20 ± 4% (decay corrected, n = 3). Radiochemical purity was > 99% and specific activity was > 400 mCi/μmol. The α/β anomer ratio was 1:2. The radiosynthesis time was about 90 min from the end of bombardment. Conclusions: A reliable microwave-assisted approach has been developed for routine synthesis of [ 18 F]-FMAU. The new approach affords a simplified process with shorter synthesis time and higher radiochemical yield as compared to conventional heating. A fully automated microwave-assisted synthesis of [ 18 F]-FMAU can be readily achieved under new reaction conditions.

6-[{sup 18}F]fluoro-A-85380: an in vivo tracer for the nicotinic acetylcholine receptor

Energy Technology Data Exchange (ETDEWEB)

Scheffel, Ursula; Horti, Andrew G.; Koren, Andrei O.; Ravert, Hayden T.; Banta, Jeffrey P.; Finley, Paige A.; London, Edythe D.; Dannals, Robert F. E-mail: robert_dannals@tracer.nm.jhu.edu

2000-01-01

6-[{sup 18}F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[{sup 18}F]fluoro-A-85380 or 6-[{sup 18}F]FA), a new tracer for positron emission tomography, was synthesized by no-carrier-added [{sup 18}F] fluorination of 6-iodo-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)methoxy)pyridine followed by acidic deprotection. 6-[{sup 18}F]FA followed the regional densities of brain nicotinic acetylcholine receptors (nAChRs) reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 6-FA. A preliminary toxicology study of the 6-FA showed a relatively low biological effect.

Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease.

Science.gov (United States)

Sato, Hiromasa; Yamamoto, Toshiyuki; Sato, Masako; Furusawa, Yoshihiko; Murata, Miho

2018-01-01

The causes of "delayed-on" and "no-on" phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. A 69-year-old man with PD presented with "delayed-on" and "no-on" phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an "off" state. Videofluoroscopic examination of swallowing in an "off" state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of "delayed-on" and "no-on" phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of "no-on" phenomena decreased. In PD patients, the "no-on" phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

Dual-time-point O-(2-[18F]fluoroethyl)-L-tyrosine PET for grading of cerebral gliomas

International Nuclear Information System (INIS)

Lohmann, Philipp; Herzog, Hans; Rota Kops, Elena; Stoffels, Gabriele; Judov, Natalie; Filss, Christian; Tellmann, Lutz; Galldiks, Norbert; Weiss, Carolin; Sabel, Michael; Coenen, Heinz Hubert; Shah, Nadim Jon; Langen, Karl-Josef

2015-01-01

We aimed to evaluate the diagnostic potential of dual-time-point imaging with positron emission tomography (PET) using O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) for non-invasive grading of cerebral gliomas compared with a dynamic approach. Thirty-six patients with histologically confirmed cerebral gliomas (21 primary, 15 recurrent; 24 high-grade, 12 low-grade) underwent dynamic PET from 0 to 50 min post-injection (p.i.) of 18 F-FET, and additionally from 70 to 90 min p.i. Mean tumour-to-brain ratios (TBR mean ) of 18 F-FET uptake were determined in early (20-40 min p.i.) and late (70-90 min p.i.) examinations. Time-activity curves (TAC) of the tumours from 0 to 50 min after injection were assigned to different patterns. The diagnostic accuracy of changes of 18 F-FET uptake between early and late examinations for tumour grading was compared to that of curve pattern analysis from 0 to 50 min p.i. of 18 F-FET. The diagnostic accuracy of changes of the TBR mean of 18 F-FET PET uptake between early and late examinations for the identification of HGG was 81 % (sensitivity 83 %; specificity 75 %; cutoff - 8 %; p < 0.001), and 83 % for curve pattern analysis (sensitivity 88 %; specificity 75 %; p < 0.001). Dual-time-point imaging of 18 F-FET uptake in gliomas achieves diagnostic accuracy for tumour grading that is similar to the more time-consuming dynamic data acquisition protocol. (orig.)

Ibuprofen or piroxicam protects nigral neurons and delays the development of l-dopa induced dyskinesia in rats with experimental Parkinsonism: Influence on angiogenesis.

Science.gov (United States)

Teema, Asmaa M; Zaitone, Sawsan A; Moustafa, Yasser M

2016-08-01

Neuroinflammation and angiogenesis have been involved in the pathogenesis of Parkinson's disease (PD). This study investigated the effect of ibuprofen or piroxicam on the motor response to l-dopa and development of dyskinesia in Parkinsonian rats focusing on the anti-angiogenic role of the two non-steroidal anti-inflammatory drugs (NSAIDs). Rats were divided into nine groups as follows: Group I: the vehicle group, Group II: rotenone group, rats were injected with nine doses of rotenone (1 mg/kg/48 h), group III&IV: rats received rotenone + ibuprofen (10 or 30 mg/kg), Group V-VI: rats received rotenone + piroxicam (1 or 3 mg/kg), Group VII: rats received rotenone + l-dopa/carbidopa (100/10 mg/kg), Group VIII-IX: rats received rotenone + l-dopa/carbidopa + ibuprofen (30 mg/kg) or piroxicam (3 mg/kg). In general, drugs were administered daily for ten weeks. Rotenone-treated rats showed motor dysfunction, lower striatal dopamine, lower staining for nigral tyrosine hydroxylase but higher level of striatal cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) compared to vehicle-treated rats (P piroxicam in combination with l-dopa preserved the effect of l-dopa at the end of week 10, delayed the development of dyskinesia and decreased striatal COX-2 and VEGF levels. In conclusion, the current study suggests that ibuprofen and piroxicam are promising candidates for neuroprotection in PD and may have utility in conjunction with l-dopa in order to ensure the longevity of its action and to delay the development of dyskinesia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Work and power reduced in L-dopa naïve patients in the early-stages of Parkinson’s disease

Directory of Open Access Journals (Sweden)

Lidiane Oliveira Lima

2016-04-01

Full Text Available ABSTRACT Studies which have investigated muscular performance during the initial stages of Parkinson´s disease (PD without L-dopa treatments were not found. Objective to assess whether muscular performance, work and power, of the trunk and lower limbs in L-dopa naïve patients in the early stages of PD was lower than those of healthy subjects and to compare muscular performance between the lower limbs. Method Ten subjects with PD, Hoehn and Yahr (HY I-II, L-dopa naïve and 10 subjects in the control group were assessed with the isokinetic dynamometer. Results ANOVAs revealed that work and power measures of the trunk, hip, knee, and ankle muscular groups were lower in PD compared with the control group (p < 0.05. There were no significant differences in muscular performance between the lower limbs. Conclusion The results suggested the use of specific exercises, as rehabilitation strategies, to improve the ability to produce work and power with this population.

Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced Parkinsonism: Role of toll-like receptor 4, TGF-β1, NF-κB and glucagon-like peptide 1.

Science.gov (United States)

Kabel, Ahmed M; Omar, Mohamed S; Alhadhrami, A; Alharthi, Salman S; Alrobaian, Majed M

2018-05-01

Our aim was to assess the effect of different doses of linagliptin with or without l-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + l-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + l-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + l-dopa/Carbidopa + linagliptin 10 mg/kg/day. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), transforming growth factor beta 1 (TGF-β1), toll-like receptor 4 (TLR4), antioxidant enzymes, adenosine triphosphate (ATP), glucagon-like peptide-1 (GLP-1), receptors of advanced glycation end products (RAGE), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), mitochondrial complex I activity, catalepsy and total swim scores were measured. Also, the substantia nigra was subjected to immunohistochemical examination. The combination of l-dopa/Carbidopa and linagliptin in a dose-dependent manner resulted in significant improvement of the behavioural changes, striatal dopamine, antioxidant parameters, Nrf2/HO-1 content, GLP-1, ATP and mitochondrial complex I activity with significant decrease in striatal RAGE, TGF-β1, TNF-α, IL-10, TLR4 and alleviated the immunohistochemical changes better than the groups that received either l-dopa/Carbidopa or linagliptin alone. The combination of l-dopa/Carbidopa and linagliptin might represent a promising therapeutic modality for management of parkinsonism. Copyright © 2018 Elsevier Inc. All rights reserved.

Preliminary Study on Purification and Identification of Aromatic Acid Amino L-Dopa From Malaysia Freshwater Green Mussel Byssus

International Nuclear Information System (INIS)

Saiful Irwan Zubairi; Wan Rosmaryana Wan Musa; Syed Anuar Faua'ad Syed Mohammad

2014-01-01

L-DOPA (L-3, 4-dihydroxyphenylalanine) is a type of aromatic amino acid which can be detected by using acidic extraction and purification method involving adhesive byssus green mussel protein. The main objective of this study is to identify and purify the aromatic amino acid L-DOPA via the utilization of gel Sephadex G-200 filtration chromatography based on two types of acidic and basic mobile phase solution. The crushing and homogenizing for adhesive byssus green mussel were conducted using a mortar and a pestle with the aid of liquid nitrogen. The samples that had been crushed were then mixed and dissolved in perchloric acid 0.7 %, 1.0 % and 1.5 % (v/ v) (pre-treatment) prior to the extraction process. The extraction was carried out by centrifuging the extracts at 11,000 rpm for about 10 mins and at a temperature of 10 degree Celsius to obtain supernatant S1. The supernatant was mixed with acetone and sulphuric acid and centrifuged for the second time to produce a pellet and then it was dissolved in the respective mobile phase solutions prior to purification process. Purification was later performed using two mobile phase solutions which were acetic acid 5 % (v/ v) and NaOH 1 M. The absorbance (abs) value of each purified protein extract fractions was collected and analysed at 214 nm to 400 nm with the help of UV-spectrophotometer. The highest abs value was selected for identification and verification of amino acid L-DOPA in the purified solution. Verification was carried out by utilizing high performance liquid chromatography (HPLC) and thin layer chromatography (TLC). The results showed that the use of 0.7 % (v/ v) perchloric acid and 5 % (v/ v) acetic acid for pre-treatment process and mobile phase solution of purification process respectively, yielded the highest effluent abs profile at a wavelength of 260 nm. TLC analysis proved the existence of several important amino acids besides L-DOPA which were tyrosine and phenylalanine after 78 hrs of collection of

Refractory epilepsy and basal ganglia: the role of seizure frequency

Energy Technology Data Exchange (ETDEWEB)

Bouilleret, V.; Trebossen, R.; Mantzerides, M.; Semah, F.; Ribeiro, M.J. [Service Hospitalier Frederic Joliot, I2BM/DSV, CEA, 91 - Orsay (France); Bouilleret, V. [CHU Bicetre, Unite de Neurophysiologie et d' Epileptologie, AP-HP, 75 - Paris (France); Chassoux, F. [Hopital Saint Anne, Service de Neurochirurgie, 75 - Paris (France); Biraben, A. [CHU, Service de Neurologie, Hopital Pontchaillou, 35 - Rennes (France)

2008-02-15

Objectives. - A decrease of [{sup 18}F]Fluoro-L-DOPA uptake in basal ganglia (B.G.) was recently reported in medically refractory epilepsy. The purpose of this study was to assess the involvement of dopaminergic neurotransmission in refractory Temporal Lobe Epilepsy (T.L.E.) and its relationship to glucose metabolism and morphological changes. Methods. - Twelve T.L.E. patients were studied using [{sup 18}F]FDG PET, [{sup 18}F]Fluoro-L-DOPA PET and MRI and compared with healthy control volunteers. Morphological cerebral changes were assessed using Voxel-Based Morphometry (V.B.M.). Student t test statistical maps of functional and morphological differences between patients and controls were obtained using a general linear model. Results. - In T.L.E. patients, [{sup 18}F]Fluoro-L-DOPA uptake was reduced to the same extent in caudate and putamen in both cerebral hemispheres as well as in the substantia nigra (S.N.). These dopaminergic functional alterations occurred without any glucose metabolism changes in these areas. The only mild morphological abnormality was found in striatal regions without any changes in the S.N.. Conclusion. - The present study provides support for dopaminergic neurotransmission involvement in T.L.E.. The discrepancies between G.M.V. atrophy and the pattern of [{sup 18}F]Fluoro-L-DOPA suggest that B.G. involvement is not related to structural subcortical abnormalities. A functional decrease can be ruled out as there was no change of the glycolytic pathway metabolism in these areas. (authors)

DAT1 polymorphism determines L-DOPA effects on learning about others' prosociality.

Directory of Open Access Journals (Sweden)

Christoph Eisenegger

Full Text Available Despite that a wealth of evidence links striatal dopamine to individualś reward learning performance in non-social environments, the neurochemical underpinnings of such learning during social interaction are unknown. Here, we show that the administration of 300 mg of the dopamine precursor L-DOPA to 200 healthy male subjects influences learning about a partners' prosocial preferences in a novel social interaction task, which is akin to a repeated trust game. We found learning to be modulated by a well-established genetic marker of striatal dopamine levels, the 40-bp variable number tandem repeats polymorphism of the dopamine transporter (DAT1 polymorphism. In particular, we found that L-DOPA improves learning in 10/10R genoype subjects, who are assumed to have lower endogenous striatal dopamine levels and impairs learning in 9/10R genotype subjects, who are assumed to have higher endogenous dopamine levels. These findings provide first evidence for a critical role of dopamine in learning whether an interaction partner has a prosocial or a selfish personality. The applied pharmacogenetic approach may open doors to new ways of studying psychiatric disorders such as psychosis, which is characterized by distorted perceptions of others' prosocial attitudes.

Plasma dihydroxyphenylalanine (DOPA) is independent of sympathetic activity in humans

DEFF Research Database (Denmark)

Eldrup, E; Christensen, N J; Andreasen, J

1989-01-01

in diabetic patients with autonomic neuropathy compared to diabetics without neuropathy, whereas baseline plasma DOPA concentrations were similar in the three groups investigated: 6.55 (5.03-7.26, median [interquartile range], n = 8) nmol l-1 in diabetics with neuropathy, 7.41 (5.79-7.97, n = 8) nmol l-1...

Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease

Directory of Open Access Journals (Sweden)

Hiromasa Sato

2018-03-01

Full Text Available Objective: The causes of “delayed-on” and “no-on” phenomena in Parkinson disease (PD are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. Case Description: A 69-year-old man with PD presented with “delayed-on” and “no-on” phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an “off” state. Videofluoroscopic examination of swallowing in an “off” state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of “delayed-on” and “no-on” phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of “no-on” phenomena decreased. Conclusion: In PD patients, the “no-on” phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

International Nuclear Information System (INIS)

Takala, Teemu O.; Nuutila, Pirjo; Pulkki, Kari; Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani; Savunen, Timo; Vaehaesilta, Tommi; Luotolahti, Matti; Kallajoki, Markku

2002-01-01

14(R,S)-[ 18 F]Fluoro-6-thia-heptadecanoic acid ([ 18 F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [ 18 F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [ 18 F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [ 18 F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [ 18 F]FTHA metabolite analysis. Fractional [ 18 F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring 18 F in the tissue samples. Fractional [ 18 F]FTHA uptake rates based on the analysis of tissue samples were 0.56±0.17 ml g -1 min -1 and 0.037±0.007 ml g -1 min -1 for myocardium and skeletal muscle (mean ± SD), respectively. The myocardial results obtained from the PET data (0.50±0.11 ml g -1 min -1 ) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%±23% (mean±SD, n=7) of the 18 F entered mitochondria in myocardium, as compared with only 36%±15% (mean±SD, n=7) in skeletal muscle. Intracellular [ 18 F]FTHA metabolite analysis showed that a major part of [ 18 F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [ 18 F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [ 18 F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only 36% of [ 18 F]FTHA accumulated in skeletal muscle appears to directly enter

The Added Diagnostic Value of 18F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors.

Science.gov (United States)

Addeo, Pietro; Poncet, Gilles; Goichot, Bernard; Leclerc, Loic; Brigand, Cécile; Mutter, Didier; Romain, Benoit; Namer, Izzie-Jacques; Bachellier, Philippe; Imperiale, Alessio

2018-04-01

The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs. Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative 18 F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and 18 F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology. There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, 18 F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, 18 F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0 ± 2.2 vs. 0.4 ± 0.7 vs. 0.6 ± 1.5, p = 0.0003). 18 F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. 18 F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

Single or combined treatment with L-DOPA and quinpirole differentially modulate expression and phosphorylation of key regulatory kinases in neuroblastoma cells.

Science.gov (United States)

Fuzzati-Armentero, Marie Therese; Ghezzi, Cristina; Nisticò, Robert; Oda, Adriano; Blandini, Fabio

2013-09-27

In the past decades, the clinical use of dopamine agonists has expanded from adjunct therapy in patients with a deteriorating response to L-3,4-dihydroxyphenylalanine (L-DOPA) to monotherapy for the treatment of early PD. Dopamine agonists provide their antiparkinsonian benefit through stimulation of brain postsynaptic type 2 dopamine receptors that exert their effect through classical cAMP-dependent mechanisms, as well as cAMP-independent cellular signaling cascades, including the Akt/glycogen synthase kinase 3 (GSK3) pathway. Alterations of Akt/GSK3 have been observed and may contribute to the neurodegenerative processes and the development of L-DOPA-induced dyskinesia. The effects L-DOPA and quinpirole, a dopamine agonist, on the two key regulatory kinases, Akt and GSK3, were evaluated in neuroblastoma cell line. L-DOPA and dopamine agonist dose-dependently and differentially modulated Akt and GSK3 expression and phosphorylation when added alone or combined. The combined treatment inverted or potentiated the modulatory properties of the single compound. The drug- and concentration-dependent balance of dopamine receptor stimulation over auto-oxidation may distinctively modulate GSK3 isoforms and Akt. Our results indicate that particular attention must be given to drug concentration and combination when multiple therapies are applied for the clinical treatment of PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Synthesis of no-carrier-added L- and D-[1-11C]-DOPA

International Nuclear Information System (INIS)

Bolster, J.M.; Vaalburg, W.; Veen, W. van; Dijk, Th. van; Molen, H.D. van der; Wynberg, H.; Woldring, M.G.; Rijksuniversiteit Groningen

1983-01-01

No-carrier-added DL-[1- 11 C]-DOPA has been synthesized by carboxylation of an α-lithioisocyanide with a radiochemical yield of up to 15% without correction for decay. The total synthesis time is 30 min. The resolution of the D- and L-isomers was accomplished within 16 min by HPLC using a chiral stationary phase and a phosphate buffer of pH 4.5 as eluent. (author)

OCCURRENCE OF L-DOPA AND DOPAMINE IN PLANTS AND CELL-CULTURES OF MUCUNA-PRURIENS AND EFFECTS OF 2,4-D AND NACL ON THESE COMPOUNDS

NARCIS (Netherlands)

WICHERS, HJ; VISSER, JF; HUIZING, HJ; PRAS, N

The development of the L-DOPA-content of roots, stems and leaves of Mucuna pruriens during growth of the plants is described. Besides L-DOPA, the leaves, but not the stems and the roots, also contain the related catechol dopamine. The time course of dopamine accumulation is compared to that of

Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism.

Science.gov (United States)

García, Carla R; Angelé-Martínez, Carlos; Wilkes, Jenna A; Wang, Hsiao C; Battin, Erin E; Brumaghim, Julia L

2012-06-07

Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates. In contrast to amino acid neurotransmitters, catecholamine neurotransmitters, L-DOPA, and curcumin prevent significant iron-mediated DNA damage (IC(50) values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC(50) values of 35 and 12.9 μM, respectively) than L-DOPA, the only catecholamine to prevent this damage (IC(50) = 73 μM). This metal-mediated DNA damage prevention is directly related to the metal-binding behaviour of these compounds. When bound to iron or copper, the catecholamines, amino acids, and curcumin significantly shift iron oxidation potentials and stabilize Fe(3+) over Fe(2+) and Cu(2+) over Cu(+), a factor that may prevent metal redox cycling in vivo. These results highlight the disparate antioxidant activities of neurotransmitters, drugs, and supplements and highlight the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders.

Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

Science.gov (United States)

Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

2012-01-01

To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

The PET / cyclotron facility at Putrajaya Hospital - an update

International Nuclear Information System (INIS)

Siti Najila Mohd Janib; Suzilawati Muhd Sarowi; Munira Shaikh Nasir; Zulkifli Mohamed Hashim

2006-01-01

Malaysia desire to have a cyclotron for nuclear medical use came into realisation recently with the establishment of a PET/Cyclotron Facility at Putrajaya Hospital. The testing and commissioning of the cyclotron, hot cells, QC equipment and PET/CT started on March 27, culminating in the first patient to be injected on May 10 2006. Three other patients were to be followed on May 15. The patients from both the Kuala Lumpur and Putrajaya Hospital were pre-selected by physicians from these hospitals. The 18 MeV cyclotron is capable of generating 16.4 MeV protons and 8.4 MeV deuterons. The cyclotron at Putrajaya has three targets (2 liquid and 1 gas) and is capable of producing 18 F-FDG and 18 F-DOPA. To complement this, the facility has 2 modules for FDG synthesis, 1 for F-DOPA and 1 for nucleophilic synthesis. The facility will be GMP compliant. For the first production for human use, the water-18 target was irradiated for 50 minutes at 20 mA to produce 1.3 Ci of F-18. At the end of synthesis, the activity of the FDG obtained was 600 mCi. The product was then injected to a 26-year-old female, with a suspected adenocarcinoma. (Author)

14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Takala, Teemu O.; Nuutila, Pirjo [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Department of Medicine, University of Turku (Finland); Pulkki, Kari [Department of Clinical Chemistry, University of Turku (Finland); Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Savunen, Timo; Vaehaesilta, Tommi [Department of Surgery, University of Turku (Finland); Luotolahti, Matti [Department of Clinical Physiology, University of Turku (Finland); Kallajoki, Markku [Department of Pathology, University of Turku (Finland)

2002-12-01

14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid ([{sup 18}F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [{sup 18}F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [{sup 18}F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [{sup 18}F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [{sup 18}F]FTHA metabolite analysis. Fractional [{sup 18}F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring {sup 18}F in the tissue samples. Fractional [{sup 18}F]FTHA uptake rates based on the analysis of tissue samples were 0.56{+-}0.17 ml g{sup -1} min{sup -1} and 0.037{+-}0.007 ml g{sup -1} min{sup -1} for myocardium and skeletal muscle (mean {+-} SD), respectively. The myocardial results obtained from the PET data (0.50{+-}0.11 ml g{sup -1} min{sup -1}) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%{+-}23% (mean{+-}SD, n=7) of the {sup 18}F entered mitochondria in myocardium, as compared with only 36%{+-}15% (mean{+-}SD, n=7) in skeletal muscle. Intracellular [{sup 18}F]FTHA metabolite analysis showed that a major part of [{sup 18}F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [{sup 18}F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [{sup 18}F]FTHA traces FFA beta-oxidation in the heart

MUCUNA PRURIENS - IMPROVEMENT OF THE BIOTECHNOLOGICAL PRODUCTION OF THE ANTI-PARKINSON DRUG L-DOPA BY PLANT-CELL SELECTION

NARCIS (Netherlands)

PRAS, N; WOERDENBAG, HJ; BATTERMAN, S; VISSER, JF; VANUDEN, W

1993-01-01

Routinely grown cell suspension cultures of Mucuna pruriens L. (Fabaceae) were able to endogenously accumulate the anti-Parkinson drug L-dihydroxyphenylalanine (L-dopa) in the range between 0.2 and 2% on a dry weight (DW) basis. The green colour that developed in light-exposed cultures, appeared to

{sup 18}F-Fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type

Energy Technology Data Exchange (ETDEWEB)

Balogova, Sona [Comenius University and St. Elisabeth Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Talbot, Jean-Noel; Michaud, Laure; Huchet, Virginie; Kerrou, Khaldoun; Montravers, Francoise [Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Nataf, Valerie [Hopital Tenon, AP-HP, Department of Radiopharmacy, Paris (France)

2013-06-15

6-Fluoro-({sup 18}F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, {sup 123}I-metaiodobenzylguanidine (MIBG) and {sup 111}In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for {sup 123}I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as

Dual-time-point O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine PET for grading of cerebral gliomas

Energy Technology Data Exchange (ETDEWEB)

Lohmann, Philipp; Herzog, Hans; Rota Kops, Elena; Stoffels, Gabriele; Judov, Natalie; Filss, Christian; Tellmann, Lutz [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); Galldiks, Norbert [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); Weiss, Carolin [University of Cologne, Department of Neurosurgery, Cologne (Germany); Sabel, Michael [Heinrich-Heine University, Department of Neurosurgery, Duesseldorf (Germany); Coenen, Heinz Hubert [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Juelich (Germany); Shah, Nadim Jon [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Juelich (Germany); RWTH Aachen University Hospital, Department of Neurology, Aachen (Germany); Langen, Karl-Josef [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Juelich (Germany)

2015-10-15

We aimed to evaluate the diagnostic potential of dual-time-point imaging with positron emission tomography (PET) using O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine ({sup 18}F-FET) for non-invasive grading of cerebral gliomas compared with a dynamic approach. Thirty-six patients with histologically confirmed cerebral gliomas (21 primary, 15 recurrent; 24 high-grade, 12 low-grade) underwent dynamic PET from 0 to 50 min post-injection (p.i.) of {sup 18}F-FET, and additionally from 70 to 90 min p.i. Mean tumour-to-brain ratios (TBR{sub mean}) of {sup 18}F-FET uptake were determined in early (20-40 min p.i.) and late (70-90 min p.i.) examinations. Time-activity curves (TAC) of the tumours from 0 to 50 min after injection were assigned to different patterns. The diagnostic accuracy of changes of {sup 18}F-FET uptake between early and late examinations for tumour grading was compared to that of curve pattern analysis from 0 to 50 min p.i. of {sup 18}F-FET. The diagnostic accuracy of changes of the TBR{sub mean} of {sup 18}F-FET PET uptake between early and late examinations for the identification of HGG was 81 % (sensitivity 83 %; specificity 75 %; cutoff - 8 %; p < 0.001), and 83 % for curve pattern analysis (sensitivity 88 %; specificity 75 %; p < 0.001). Dual-time-point imaging of {sup 18}F-FET uptake in gliomas achieves diagnostic accuracy for tumour grading that is similar to the more time-consuming dynamic data acquisition protocol. (orig.)

Enantiomeric determination of DOPA in dietary supplements containing Mucuna pruriens by liquid chromatography/mass spectrometry.

Science.gov (United States)

Hasegawa, Takashi; Takahashi, Kazunaga; Fukiwake, Tomohide; Saijo, Masaaki; Motoki, Yuji

2013-01-01

We developed a simple and rapid liquid chromatography/mass spectrometry (LC/MS) method for the enantiomeric determination of DOPA in dietary supplements containing Mucuna pruriens. L- and D-DOPA were ultrasonically extracted with 1% formic acid aqueous solution. The isolated extracts were analyzed by LC/MS using a Crownpak CR (-) column at 30℃. The mass spectrometer was operated in the positive mode of electrospray ionization, and the mobile phase was aqueous formic acid (pH 2.0). L-DOPA-ring-d3 was used as an internal standard. The method was validated for a dietary supplement spiked with L- and D-DOPA at 50 and 500 μg/g, respectively, and the recoveries of the DOPA enantiomers were between 97.5% and 101.3%. Relative standard deviation values of repeatability and intermediate precision were less than 7%. The method was applied to 14 dietary supplements. L-DOPA was detected in these supplements in the range of 0.88-12.8 mg/unit. D-DOPA was not detected.

Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

Science.gov (United States)

Wegner, Florian; Wilke, Florian; Raab, Peter; Tayeb, Said Ben; Boeck, Anna-Lena; Haense, Cathleen; Trebst, Corinna; Voss, Elke; Schrader, Christoph; Logemann, Frank; Ahrens, Jörg; Leffler, Andreas; Rodriguez-Raecke, Rea; Dengler, Reinhard; Geworski, Lilli; Bengel, Frank M; Berding, Georg; Stangel, Martin; Nabavi, Elham

2014-06-20

Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

PET imaging of dopamine transporters with [18F]FE-PE2I: Effects of anti-Parkinsonian drugs

International Nuclear Information System (INIS)

Bang, Ji-In; Jung, In Soon; Song, Yoo Sung; Park, Hyun Soo; Moon, Byung Seok; Lee, Byung Chul; Kim, Sang Eun

2016-01-01

Purpose: This study aimed to assess the striatal [ 18 F]FE-PE2I binding and the immunohistochemical stain of tyrosine hydroxylase (TH) in the striatum, and to evaluate the effects of therapeutic drugs on [ 18 F]FE-PE2I binding. Methods: Dynamic PET/CT of [ 18 F]FE-PE2I was performed in Parkinson’s disease (PD) rat models, induced by the unilateral injection of 6-OHDA into the striatum. A simplified reference tissue model method was used to calculate the striatal binding potential (striatal BP ND ). Each of the four normal rats was pretreated with pramipexole, amantadine, and escitalopram 30 min before [ 18 F]FE-PE2I injection. The effect of L-DOPA combined with benserazide was assessed in the normal and PD rats. Results: The BP ND was significantly lower in the lesioned striatum than in the striatum of the normal rats. After the pretreatment with pramipexole, amantadine, and escitalopram, the values of the striatal BP ND did not differ from those of the controls. The pretreatment with L-DOPA/benserazide, however, significantly reduced the striatal BP ND . The striatal BP ND of the PD rats with L-DOPA/benserazide pretreatment was not different from that of the same PD rats with placebo treatment. Conclusion: [ 18 F]FE-PE2I may be used as a radioligand for the in-vivo imaging of the DAT. In the normal rats, [ 18 F]FE-PE2I binding is unaffected by pramipexole, amantadine, and escitalopram. L-DOPA/benserazide does not affect the striatal [ 18 F]FE-PE2I binding in PD rats

Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

Directory of Open Access Journals (Sweden)

Anna Ljungdahl

Full Text Available L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors

Parametric imaging of the rate constant K[sub i] using 18Fluoro-L-dopa positron emission tomography in progressive supranuclear palsy

Energy Technology Data Exchange (ETDEWEB)

Cordes, M. (Neurodegenerative Disorders Centre, Univ. Hospital, Univ. of British Columbia, Vancouver, BC (Canada) Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf-Virchow, Berlin (Germany)); Snow, B.J. (Neurodegenerative Disorders Centre, Univ. Hospital, Univ. of British Columbia, Vancouver, BC (Canada)); Morrison, S. (TRIUMF, Univ. of British Columbia, Vancouver, BC (Canada)); Sossi, V. (TRIUMF, Univ. of British Columbia, Vancouver, BC (Canada)); Ruth, T.J. (TRIUMF, Univ. of British Columbia, Vancouver, BC (Canada)); Calne, D.B. (Neurodegenerative Disorders Centre, Univ. Hospital, Univ. of British Columbia, Vancouver, BC (Canada))

1993-01-01

Positron emission tomography (PET) studies using 18F-L-dopa were carried out in 9 patients with supranuclear palsy and 13 controls. For quantification of PET data a rate constant K[sub i] was calculated for the radiotracer using a graphical method. Corrections for nonspecific activity were performed in both arterial plasma and brain tissue. The purpose of this study was to test the hypothesis that parametric images of the rate constant K mapping can be obtained on a pixel-by-pixel basis using an appropriate mathematical algorithm. K[sub i] values from these parametric images and the graphical approach were compared. Both correlated closely, with y=0.013+0.947[sup *]x, r=0.992 and y=-0.052+1.048[sup *]x, r=0.965 in patients and controls, respectively. Contrast measurements were also performed and showed a striking increase in contrast on parametric images. K mapping offers several advantages over the graphical approach, since parametric images are time-independent, i.e. one image represents the quantitative result of the study. In addition, parmetric images of the rate constant are normalized to arterial plasma radioactivity and corrected for tissue metabolites. Thus, parametric images of K[sub i] in different individuals can be compared directly without further processing in order to assess the nigrostriatal integrity. (orig.)

Mapping of central dopamine synthesis in man, using positron emission tomography with L-[β-11C]DOPA

International Nuclear Information System (INIS)

Ito, Hiroshi; Shidahara, Miho; Takano, Harumasa; Takahashi, Hidehiko; Nozaki, Shoko; Suhara, Tetsuya

2007-01-01

The objective of this study was to estimate the presynaptic function of the central dopaminergic system, positron emission tomography measurement of the endogenous dopamine synthesis rate was performed with L-[β- 11 C]dihydroxyphenylanine (DOPA). In the present study, we developed a simple method for calculating an indicator of the dopamine synthesis rate with L-[β- 11 C]DOPA on a voxel-by-voxel basis for parametric mapping. After intravenous injection of L-[β- 11 C]DOPA, dynamic scanning was performed on ten healthy men for 89 min. The dopamine synthesis ratio was calculated on a voxel-by-voxel basis as the ratio of the area under the time-activity curves of brain regions to the reference brain region, that is, occipital cortex. The overall uptake rate constant as an indicator of dopamine synthesis was also calculated by kinetic and graphical analyses. The dopamine synthesis ratio calculated by the present method was in good agreement with the indicators of dopamine synthesis calculated by kinetic and graphical analyses, although a systemic underestimation was observed, especially when the integration interval was set in the early phase of the scan duration. In particular, underestimations were prominent in brain regions with relatively lower influx rate constant K 1 . By this method, regional dopamine synthesis could be estimated on a voxel-by-voxel basis. This method does not need an arterial input function and should prove to be useful for clinical research. (author)

[Deep brain stimulation in parkinsonian patients with dopa intolerance].

Science.gov (United States)

García-Ruiz, Pedro J; Feliz-Feliz, Cici; Ayerbe Gracia, Joaquín; Matías Arbelo, José; Salvador, Carlos; Val Fernández, Javier Del; García-Caldentey, Juan

2017-10-28

Deep brain stimulation (DBS) is at present, a useful treatment for patients with advanced Parkinson's disease and motor complications. The crucial step toward consistent DBS outcomes remains careful patient selection; several conditions must be fulfilled including excellent levo dopa response. We report two cases of early onset Parkinson's disease with severe intolerance to levo dopa but excellent and sustained response to DBS. DBS can be a useful alternative for parkinsonian patients with severe intolerance to levo dopa, provided a positive acute response to levo dopa or apomorphine is obtained. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Involuntary expiratory phonation as a dose-related consequence of L-dopa therapy in a patient with Parkinson's disease.

Science.gov (United States)

Ishii, Kosuke; Kumada, Masanobu; Ueki, Akira; Yamamoto, Masanori; Hirose, Hajime

2003-12-01

We report a case of involuntary phonation caused by abnormal vocal cord movements during expiration in a patient with Parkinson's disease. A 60-year-old woman had been treated for parkinsonism at the outpatient clinic of the Department of Neurology since August 1999. She began to groan involuntarily in the daytime in September 2001. She could not eat well while groaning. Stridor was not noted during sleep at night. Endoscopic examination of the larynx revealed insufficient abduction of the bilateral vocal cords, although the glottis was not so small as to cause stridor during inspiration. During expiration, however, the vocal cords adducted, resulting in the involuntary production of voice. Electromyography showed an increase in the activity of the thyroarytenoid and lateral cricoarytenoid muscles. This muscle activity was further enhanced during inspiration. The involuntary phonation disappeared when the patient's dose of L-dopa was decreased, although she had a decrease in her systemic mobility as well. When the dose of L-dopa was increased to the therapeutic level, involuntary phonation recurred, and her voluntary systemic activity improved. In the present case, it was considered that excessive dopaminergic denervation occurred in the nerve innervating the laryngeal adductors. Involuntary voice appeared to be produced by hypertonus of the laryngeal adductors because of a lowering in the threshold level for L-dopa, even though the drug was administered at the usual dose.

Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

Science.gov (United States)

Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

2010-09-15

The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

Variation of L-DOPA in the leaf and flower tissues of seven faba bean accessions with different flower colors

Science.gov (United States)

Faba bean (Vicia faba L.) has been selected to adapt to a wide range of environments worldwide and is grown for different end-uses such as food, feed, forage and green manure. Particularly noteworthy in faba bean is the medicinally important component L-3,4-dihydroxy phenylalanine (L-DOPA), the majo...

18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.

Science.gov (United States)

Rodrigues, Rosana S; Bozza, Fernando A; Hanrahan, Christopher J; Wang, Li-Ming; Wu, Qi; Hoffman, John M; Zimmerman, Guy A; Morton, Kathryn A

2017-05-01

Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Significant uptake of 18 F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14 C-2DG uptake in activated neutrophils. 18 F

A single one-step radiosynthesis of [{sup 18}F]L.B.T.-999, a novel and selective dat radioligand for PET

Energy Technology Data Exchange (ETDEWEB)

Dolle, F.; Hinnen, F.; Saba, W.; Schollhorn-peyronneau, M.A.; Valette, H.; Bottlaender, M. [Service Hospitalier Frederic Joliot, DSV/ Institut d' Imagerie BioMedicale, 91 - Orsay (France); Helfenbein, J.; Le gailliard, J. [Institut National de la Sante et de la Recherche Medicale (INSERM), U484, Orphachem, ZATE, 63 - Clermont Ferrand (France); Mavel, S.; Mincheva, Z.; Garreau, L.; Chalon, S.; Guilloteau, D.; Emond, P. [Institut National de la Sante et de la Recherche Medicale (INSERM), U619, 37 - Tours (France); Mavel, S.; Garreau, L.; Chalon, S.; Guilloteau, D.; Emond, P. [Universite Francois Rabelais de Tours, 37 (France); Halldin, C. [Karolinska Institut, Dept. of Clinical Neuroscience, Karolinska Hospital, Stockholm (Sweden); Madelmont, J.C. [Institut National de la Sante et de la Recherche Medicale (INSERM) U484, Lab. Etude Metabolique des Molecules Marquees, 63 - Clermont Ferrand (France); Deloye, J.B. [Biopole Clermont Limagne, Lab. Cyclopharma, 63 - Saint Beauzire (France); Guilloteau, D. [Centre Hospitalier Regional Universitaire, 37 - Tours (France)

2008-02-15

L.B.T.-999 (8-((E)-4-fluoro-but-2-enyl)-3-beta-p-tolyl-8- aza-bi-cyclo[3.2.1]octane-2-beta-carboxylic acid methyl ester) is a recently developed cocaine derivative belonging to a new generation of highly selective D.A.T. ligands [1-3]. Initial fluorine-18-labelling of L.B.T.-999 was based on the robust and reliable two-step radiochemical pathway often reported for such tropane derivatives, involving first the preparation of (E)-1-[{sup 18}F]fluoro-4-tosyloxybut-2-ene followed by a N-alkylation reaction with the appropriate nor-tropane moiety [4]. In the present work, a simple one-step fluorine-18-labelling of L.B.T.-999 is reported, based on a chlorine-for-fluorine nucleophilic aliphatic substitution, facilitating as expected both automation and final H.P.L.C. purification. The process involves: (A) reaction of K[{sup 18}F]F-Kryptofix 222 with the chlorinated precursor (3.5-4.5 mg) at 165 degrees C for 10 min in D.M.S.O. (0.6 m L) followed by (B) C-18 PrepSep cartridge pre-purification and finally (C) semi preparative HPLC purification on a Waters Symmetry C-18. Typically, 3.70-5.92 GBq of [{sup 18}F]L.B.T.-999 (> 95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111 GBq/micro-mol within 85-90 min (HPLC purification and Sep-Pak-based formulation included), starting from a 37.0 GBq [{sup 18}F]fluoride batch (overall radiochemical yields: 10-16%, non decay corrected) [5].Supported in part by the E.C. - F.P.6-project D.i.M.I. (L.S.H.B.-C.T.- 2005-512146) and the R.N.T.S. 03 B 243 Fluoropak program. (authors)

Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor binding measured by positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Shinotoh, H; Asahina, M; Hirayama, K [Dept. of Neurology, School of Medicine, Chiba Univ., Chiba (Japan); Inoue, O; Suhara, T; Tateno, Y [Division of Clinical Research, National Inst. of Radiological Sciences, Chiba (Japan)

1994-01-01

The effects of pharmacological intervention on brain muscarinic cholinergic receptor (mAChR) binding were assessed in seven patients with Parkinson's disease by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl benzilate ([[sup 11]C]NMPB). [[sup 11]C]NMPB was injected twice, approximately 2 hours apart, in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl (n=5) or 400 mg of L-dopa with 57 mg of benserazide (n=2) on the binding parameter of mAChRs (K[sub 3]). There was a mean 28% inhibition of K[sub 3] values in the brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR occupancy. No significant change in K[sub 3] was observed in the presence of L-dopa. This study demonstrates the feasibility of measuring mAChR occupancy by an anticholinergic medication with PET.

Metabolic mapping of functional activity in human subjects with the [18F]fluorodeoxyglucose technique

International Nuclear Information System (INIS)

Greenberg, J.H.; Reivich, M.; Alavi, A.

1981-01-01

The 2-[ 18 F]fluoro-2-deoxy-D-glucose technique was used to measure regional cerebral glucose utilization by human subjects during functional activation. Normal male volunteers subjected to one or more sensory stimuli exhibited focal increases in glucose metabolism in response to the stimulus. These results demonstrate that the technique is capable of providing functional maps in vivo related to both body region and submodality of sensory information in the human brain

Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

Science.gov (United States)

Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

2016-08-01

The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

Protective effect of two essential oils isolated from Rosa damascena Mill. and Lavandula angustifolia Mill, and two classic antioxidants against L-dopa oxidative toxicity induced in healthy mice.

Science.gov (United States)

Nikolova, Galina; Karamalakova, Yanka; Kovacheva, Natasha; Stanev, Stanko; Zheleva, Antoaneta; Gadjeva, Veselina

2016-11-01

Levodopa (L-dopa) is a "gold standard" and most effective symptomatic agent in the Parkinson's disease (PD) treatment. The several treatments have been developed in an attempt to improve PD treatment, but most patients were still levodopa dependent. The issue of toxicity was raised in vitro studies, and suggests that L-dopa can be toxic to dopaminergic neurons, but it is not yet entirely proven. L-dopa prolonged treatment is associated with motor complications and some limitations. Combining the L-dopa therapy with antioxidants can reduce related sideeffects and provide symptomatic relief. The natural antioxidants can be isolated from any plant parts such as seeds, leaves, roots, bark, etc., and their extracts riched in phenols can retard the oxidative degradation of the lipids, proteins and DNA. Thus, study suggests that combination of essential oils (Rose oil and Lavender oil), Vitamin C and Trolox with Ldopa can reduce oxidative toxicity, and may play a key role in ROS/RNS disarm. Copyright © 2016 Elsevier Inc. All rights reserved.

Overexpression of blood microRNAs 103a, 30b, and 29a in L-dopa-treated patients with PD.

Science.gov (United States)

Serafin, Alice; Foco, Luisa; Zanigni, Stefano; Blankenburg, Hagen; Picard, Anne; Zanon, Alessandra; Giannini, Giulia; Pichler, Irene; Facheris, Maurizio F; Cortelli, Pietro; Pramstaller, Peter P; Hicks, Andrew A; Domingues, Francisco S; Schwienbacher, Christine

2015-02-17

The aims of the present study were to profile the expression of several candidate microRNAs (miRNAs) in blood from L-dopa-treated and drug-naive patients with Parkinson disease (PD) vs unaffected controls and to interpret the miRNA expression data in a biological context. We analyzed RNAs from peripheral blood of 36 L-dopa-treated, 10 drug-naive patients with PD and unaffected controls matched 1:1 by sex and age. We evaluated expression by reverse transcription-quantitative real-time PCR, and we analyzed data using a 2-tailed paired t test. To detect miRNA targets, several miRNA resources were combined to generate an overall score for each candidate gene using weighted rank aggregation. Significant overexpression of miR-103a-3p (p < 0.0001), miR-30b-5p (p = 0.002), and miR-29a-3p (p = 0.005) in treated patients with PD was observed, and promising candidate target genes for these were revealed by an integrated in silico analysis. We revealed 3 candidate biomarkers for PD. miRNAs 30b-5p and 29a-3p replicated a documented deregulation in PD albeit opposite to published data, while for miR-103a-3p, we demonstrated for the first time an overexpression in treated patients with PD. Expression studies in patients and/or in isolated peripheral blood mononuclear cells before and after L-dopa administration are necessary to define the involvement of L-dopa treatment in the observed overexpression. Our in silico analysis to prioritize targets of deregulated miRNAs identified candidate target genes, including genes related to neurodegeneration and PD. Despite the preliminary character of our study, the results provide a rationale for further clarifying the role of the identified miRNAs in the pathogenesis of PD and for validating their diagnostic potential. © 2015 American Academy of Neurology.

In vivo detection of cranial dopaminergic processes: studies with L-1-C-11-Dopa and C-11-labelled ADTN derivatives

International Nuclear Information System (INIS)

Werf, J.F.v.d.; Kuilman, T.; Molen, H.D.v.d.; Paans, A.M.J.; Wiegman, T.; Korf, J.; Vaalburg, W.

1982-01-01

In this article, probably the first in literature, some results are presented of in vivo studies of carbon-11-labelled dopamine agonists in cats and dogs with positron emission tomography. Recently a method for the separation of D- and L-dopa enantiomers from the DL-dopa mixture was developed. These three compounds were injected intravenously and with PET cold spots in the striatium of dog's brains could be obtained, independently of pretreatment with carbidopa. The synthesis of carbon-11-labelled ADTN derivatives and their uses is discussed. (Auth.)

Influence of basal ganglia on upper limb locomotor synergies. Evidence from deep brain stimulation and L-DOPA treatment in Parkinson's disease.

Science.gov (United States)

Crenna, P; Carpinella, I; Lopiano, L; Marzegan, A; Rabuffetti, M; Rizzone, M; Lanotte, M; Ferrarin, M

2008-12-01

Clinical evidence of impaired arm swing while walking in patients with Parkinson's disease suggests that basal ganglia and related systems play an important part in the control of upper limb locomotor automatism. To gain more information on this supraspinal influence, we measured arm and thigh kinematics during walking in 10 Parkinson's disease patients, under four conditions: (i) baseline (no treatment), (ii) therapeutic stimulation of the subthalamic nucleus (STN), (iii)L-DOPA medication and (iv) combined STN stimulation and L-DOPA. Ten age-matched controls provided reference data. Under baseline conditions the range of patients' arm motion was severely restricted, with no correlation with the excursion of the thigh. In addition, the arm swing was abnormally coupled in time with oscillation of the ipsilateral thigh. STN stimulation significantly increased the gait speed and improved the spatio-temporal parameters of arm and thigh motion. The kinematic changes as a function of gait speed changes, however, were significantly smaller for the upper than the lower limb, in contrast to healthy controls. Arm motion was also less responsive after L-DOPA. Simultaneous deep brain stimulation and L-DOPA had additive effects on thigh motion, but not on arm motion and arm-thigh coupling. The evidence that locomotor automatisms of the upper and lower limbs display uncorrelated impairment upon dysfunction of the basal ganglia, as well as different susceptibility to electrophysiological and pharmacological interventions, points to the presence of heterogeneously distributed, possibly partially independent, supraspinal control channels, whereby STN and dopaminergic systems have relatively weaker influence on the executive structures involved in the arm swing and preferential action on those for lower limb movements. These findings might be considered in the light of phylogenetic changes in supraspinal control of limb motion related to primate bipedalism.

From L-dopa to dihydroxyphenylacetaldehyde: a toxic biochemical pathway plays a vital physiological function in insects.

Directory of Open Access Journals (Sweden)

Christopher Vavricka

2011-01-01

Full Text Available One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD family based on extremely high sequence homology (∼70% with dopa decarboxylase (Ddc, was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects.

18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury genetic algorithm

International Nuclear Information System (INIS)

Rodrigues, Rosana S.; Bozza, Fernando A.; Hanrahan, Christopher J.; Wang, Li-Ming; Wu, Qi; Hoffman, John M.; Zimmerman, Guy A.; Morton, Kathryn A.

2017-01-01

Introduction: Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Methods: Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24 h following the intraperitoneal injection of 10 mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Results: Significant uptake of 18 F-FDG occurred by 2 h following LPS, and progressively increased to 24 h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Conclusion: Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. Advances in knowledge and implications for patient care: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14

Three-dimensional patterns of speech-induced cerebral and cerebellar activation in healthy volunteers and in aphasic stroke patients studied by positron emission tomography of 2(18F)-fluorodeoxyglucose

International Nuclear Information System (INIS)

Pawlik, G.; Heiss, W.D.; Beil, C.; Gruenewald, G.; Herholz, K.; Wienhard, K.; Wagner, R.

1987-01-01

Eight healthy male volunteers and eight moderately aphasic patients with a single cerebral infarctions in the postacute stage, were studied by dynamic positron emission tomography (PET) using the 2(18F)-fluoro-2-deoxy-D-glucose method and a 7-slice positron camera. Because hemispheric speech dominance is commonly thought to be closely related to handedness, subjects were tested by the Oldfield and Bryden questionnaires; the volunteers also had a tracking and pin-sort test. PET studies were performed in random order, both at rest and during spontaneous speech of rather abstract and some biographic content, with a time interval of 2 to 7 days between measurements of the same individual. Data was analyzed by means of weighted, repeated measures of analysis of variance (ANOVA). 11 refs.; 2 figs

The functional neuroanatomy of verbal memory in Alzheimer's disease: [18F]-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) correlates of recency and recognition memory.

Science.gov (United States)

Staffaroni, Adam M; Melrose, Rebecca J; Leskin, Lorraine P; Riskin-Jones, Hannah; Harwood, Dylan; Mandelkern, Mark; Sultzer, David L

2017-09-01

The objective of this study was to distinguish the functional neuroanatomy of verbal learning and recognition in Alzheimer's disease (AD) using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning task. In 81 Veterans diagnosed with dementia due to AD, we conducted a cluster-based correlation analysis to assess the relationships between recency and recognition memory scores from the CERAD Word Learning Task and cortical metabolic activity measured using [ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). AD patients (Mini-Mental State Examination, MMSE mean = 20.2) performed significantly better on the recall of recency items during learning trials than of primacy and middle items. Recency memory was associated with cerebral metabolism in the left middle and inferior temporal gyri and left fusiform gyrus (p recognition memory was correlated with metabolic activity in two clusters: (a) a large cluster that included the left hippocampus, parahippocampal gyrus, entorhinal cortex, anterior temporal lobe, and inferior and middle temporal gyri; (b) the bilateral orbitofrontal cortices (OFC). The present study further informs our understanding of the disparate functional neuroanatomy of recency memory and recognition memory in AD. We anticipated that the recency effect would be relatively preserved and associated with temporoparietal brain regions implicated in short-term verbal memory, while recognition memory would be associated with the medial temporal lobe and possibly the OFC. Consistent with our a priori hypotheses, list learning in our AD sample was characterized by a reduced primacy effect and a relatively spared recency effect; however, recency memory was associated with cerebral metabolism in inferior and lateral temporal regions associated with the semantic memory network, rather than regions associated with short-term verbal memory. The correlates of recognition memory included the medial temporal lobe

Colorimetric detection of manganese(II) ions using gold/dopa nanoparticles.

Science.gov (United States)

Narayanan, Kannan Badri; Park, Hyun Ho

2014-10-15

We report here a one-pot, greener, eco-friendly strategy for the synthesis of gold nanoparticles using L-dopa. The as-prepared dopa-functionalized gold nanoparticles (AuNPs/dopa) can detect low concentrations of manganese(II) metal ions in aqueous solution. The binding forces between dopa and Mn(2+) ions cause dopa-functionalized gold nanoparticles to come closer together, decreasing the interparticle distance and aggregating it with a change in color of colloidal solution from red to purplish-blue. Dynamic light scattering (DLS) analysis showed a decreased surface charge on the surface of gold nanoparticles when exposed to Mn(2+) ions, which caused cross-linking aggregation. Transmission electron microscopic (TEM) images also revealed the aggregation of gold nanoparticles with the addition of Mn(2+) ions. The extinction ratio of absorbance at 700-550nm (A700/A550) was linear against the concentration of [Mn(2+)] ions. Thus, the optical absorption spectra of gold colloidal solution before and after the addition of Mn(2+) ions reveal the concentration of Mn(2+) ions in solution. Copyright © 2014 Elsevier B.V. All rights reserved.

The application of PET, SPECT and MRS in Parkinson's disease

International Nuclear Information System (INIS)

Dong Aisheng; Tian Jianming

2005-01-01

PET and SPECT provide the means to studying in vivo the neurochemical, hemodynamic or metabolic consequences of the degeneration of the nigrostriatal dopamineric system in Parkinson's disease (PD). Activation studies using cerebral blood flow and metabolism measurements during a motor task reveal an impaired ability to activate the supplementary motor area and dorsolateral prefrontal cortex in PD. The extent of striatal dopaminergic denervation can be quantified with PET and SPECT. Striatal uptake of 18 F-dopa is markedly decreased in PD, more in the putamen than in the caudate nucleus, and inversely correlates with the severity of motor signs and with duration of disease. PET and SPECT make possible the assessment by noninvasive means of the changes in dopamine receptor density. Meanwhile, MRS can reveal changes in concentration of several hydrogenate and phosphoric compounds in the brain. The functional information of brain in PD can be obtained with these complementary techniques. (authors)

Comparison of 18F-FET PET and 5-ALA fluorescence in cerebral gliomas

International Nuclear Information System (INIS)

Floeth, Frank Willi; Sabel, Michael; Steiger, Hans Jakob; Ewelt, Christian; Stummer, Walter; Felsberg, Joerg; Reifenberger, Guido; Stoffels, Gabriele; Langen, Karl-Josef; Coenen, Heinz Hubert

2011-01-01

The aim of the study was to compare presurgical 18 F-fluoroethyl-L-tyrosine ( 18 F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas. 18 F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for 18 F-FET or Gd and checked for 5-ALA fluorescence. 18 F-FET uptake with a mean tumour to brain ratio ≥1.6 was rated as positive. Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III (n = 19) or IV (n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, 18 F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, 18 F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on 18 F-FET PET. There are differences between 18 F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. 18 F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning. (orig.)

Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

Science.gov (United States)

Rukavina Mikusic, Natalia L; Kouyoumdzian, Nicolás M; Del Mauro, Julieta S; Cao, Gabriel; Trida, Verónica; Gironacci, Mariela M; Puyó, Ana M; Toblli, Jorge E; Fernández, Belisario E; Choi, Marcelo R

2018-01-01

Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na + , K + -ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload. Copyright © 2017 Elsevier Inc. All rights reserved.

Phase IIa Clinical Trial of Trans-1-Amino-3-18F-Fluoro- Cyclobutane Carboxylic Acid in Metastatic Prostate Cancer

Directory of Open Access Journals (Sweden)

Yusuke Inoue

2014-10-01

Full Text Available Objective(s: We performed a phase IIa clinical trial of trans-1-amino-3-18Ffluoro-cyclobutane carboxylic acid (anti-18F-FACBC, a synthetic amino acid analog for PET, in patients with metastatic prostate cancer. Methods: The study subjects consisted of 10 untreated prostate cancer patients having lymph node and/or bone metastasis. Five patients underwent whole-body PET 5 and 30 min after intravenous injection of anti-18F-FACBC. The other five patients underwent 60 min dynamic PET of the pelvis. Safety assessment was performed before and 24 h after injection. PET/CT images were assessed visually, and time courses of anti-18F-FACBC uptake were evaluated from dynamic imaging. Results: Two mild adverse events were observed and resolved without treatment. All 10 patients showed increased accumulation of anti-18F-FACBC in the primary prostate lesion. CT revealed five enlarged lymph nodes indicating metastasis, and all showed increased uptake. Additionally, anti-18F-FACBC PET delineated unenlarged lymph nodes as hot spots. Anti-18F-FACBC PET demonstrated metastatic bone lesions, similar to conventional imaging. In one of two patients with lung metastasis, some lesions showed increased uptake. Regarding the time course, increased uptake of anti-18F-FACBC in the lesion was demonstrated immediately after injection, followed by gradual washout. Conclusion: The results of this phase IIa clinical trial indicated the safety of anti-18F-FACBC in patients with prostate cancer and the potential of anti-18F-FACBC PET to delineate primary prostate lesions and metastatic lesions. This clinical trial was registered as JapicCTI-101326.

Positron Emission Tomography (PET) Experience with 2-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]FA) in the Living Human Brain of Smokers with Paranoid Schizophrenia

Science.gov (United States)

BRAŠIĆ, JAMES ROBERT; CASCELLA, NICOLA; KUMAR, ANIL; ZHOU, YUN; HILTON, JOHN; RAYMONT, VANESSA; CRABB, ANDREW; GUEVARA, MARIA RITA; HORTI, ANDREW G.; WONG, DEAN FOSTER

2012-01-01

Utilizing postmortem data (Breese, et al., 2000), we hypothesized that the densities of high-affinity neuronal α4β2 nicotinic acetylcholine receptors (nAChRs) in the brain exist in a continuum from highest to lowest as follows: smokers without schizophrenia > smokers with schizophrenia > nonsmokers without schizophrenia > nonsmokers with schizophrenia. Application of the Kruskal-Wallis Test (Stata, 2003) to the postmortem data (Breese, et al., 2000) confirmed the hypothesized order in the cortex and the hippocampus and attained significance in the caudate and the thalamus. Positron emission tomography (PET) was performed for 60 minutes at 6 hours after the intravenous administration of 444 megabequerels [MBq] (12 mCi) 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]FA), a radiotracer for high-affinity neuronal α4β2 nAChRs, as a bolus plus continuous infusion to 10 adults (7 men and 3 women) (6 smokers including 5 with paranoid schizophrenia and 4 nonsmokers) ranging in age from 22 to 56 years (mean 40.1, standard deviation 13.6). The thalamic nondisplaceable binding potential (BPND) was 1.32 ± 0.19 (mean ± standard deviation) for healthy control nonsmokers; 0.50 ± 0.19 for smokers with paranoid schizophrenia; and 0.51 for the single smoker without paranoid schizophrenia. The thalamic BPNDs of nonsmokers were significantly higher than those of smokers who smoked cigarettes a few hours before the scans (P = 0.0105) (StataCorp, 2003), which was likely due to occupancy of nAChRs by inhaled nicotine in smokers. Further research is needed to rule out the effects of confounding variables. PMID:22169936

18F-FDG-PET Correlates of Impulse Control Disorder in a Diabetic Patient.

Science.gov (United States)

Yulug, Burak; Hanoglu, Lütfü; Tavlı, Ahmet Mithat; Cakir, Tansel; Khanmammadov, Elmir; Olmuscelik, Oktay

2016-01-01

Studies have already shown that hyperglycemia and insulin resistance are significantly associated with the impairment of cerebral glucose metabolism that may secondary lead to cognitive disturbances. In this study, we aimed to evaluate the neurometabolic correlates of diabetes in a patient with Intermittent explosive disorder (IED). We have investigated the cerebral glucose metabolism via 2-[18F]-fluoro-2- deoxy-D-glucose positron emission tomography (FDG-PET) in a diabetic patient with aggressive outbursts. We have found significantly reduced glucose uptake in left temporoparietal region, pontin area, and left nucleus lentiformis. Our present results indicate decreased cerebral glucose metabolism in specific cerebral cortical and subcortical areas. The main limitation of this report is that, this is a single case study and that these findings need to be replicated in well- conducted randomized controlled studies by using additional neuroquantitative methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Análise acústica da prosódia em mulheres com doença de Parkinson: efeito da Levodopa Acoustic analysis of prosody in females with Parkinson's disease: effect of L-dopa

Directory of Open Access Journals (Sweden)

Luciana L. Azevedo

2003-12-01

Full Text Available MOTIVO DO ESTUDO: Pacientes com doença de Parkinson (DP apresentam anormalidades da fala caracterizadas por pequena variação da frequência fundamental (Fo e maior amplitude. O papel dos sistemas dopaminérgicos na patogênese dessas alterações e o efeito terapêutico da L-dopa não se encontram claramente determinados. O objetivo desta investigação é avaliar o efeito da L-dopa nas caraterísticas da prosódia de mulheres com DP. MÉTODO: Nós estudamos 8 mulheres com DP (68,4 ± 6,4 anos e 8 mulheres controles (63,5 ± 6,8 anos. As pacientes (estágio H-Y 2, uma; estágio 2,5, quatro; estágio 3, três foram examinadas quando off e on. A frequência fundamental intensidade e duração da fala de sentenças afirmativas foram analisadas com o programa WinPitch 1.8 (Philippe Martin®. Os parâmetros Fo analisados foram: Fo usual (Fo us, Fo máxima (Fo max, Fo mínima (Fo min, Fo max da tônica prénuclear (Fo max PNT, Fo min da tônica prénuclear (Fo min PNT, Fo max da tônica nuclear (Fo max NT, Fo min da tônica nuclear (Fo min TN, velocidade da variação melódica da PNT (VPNT, velocidade da variação melódica da NT (VNT, amplitude da variação melódica da PNT (APNT, e amplitude da variação melódica da NT (ANT. Duração da sentença (D, duração da PNT (DPNT, duração da NT (DNT e número de sílabas por segundo (NSS foram os parâmetros de duração investigados. Foram estudadas as seguintes variáveis da intensidade: intensidade média (MI, intensidade máxima (I max, intensidade mínima (I min, intensidade da PNT (IPNT e intensidade da NT (INT. Diferenças foram estatisticamente significativas se pBACKGROUND: Untreated Parkinson's disease (PD patients display speech abnormalities characterized by narrow range of fundamental frequency (Fo variation and higher amplitude. The role of dopaminergic systems in the pathogenesis of these changes as well as the therapeutic effect of L-dopa have not been clearly determined. The aim

Development & automation of a novel ["1"8F]F prosthetic group, 2-["1"8F]-fluoro-3-pyridinecarboxaldehyde, and its application to an amino(oxy)-functionalised Aβ peptide

International Nuclear Information System (INIS)

Morris, Olivia; Gregory, J.; Kadirvel, M.; Henderson, Fiona; Blykers, A.; McMahon, Adam; Taylor, Mark; Allsop, David; Allan, Stuart; Grigg, J.; Boutin, Herve; Prenant, Christian

2016-01-01

2-["1"8F]-Fluoro-3-pyridinecarboxaldehyde (["1"8F]FPCA) is a novel, water-soluble prosthetic group. It's radiochemistry has been developed and fully-automated for application in chemoselective radiolabelling of amino(oxy)-derivatised RI-OR2-TAT peptide, (Aoa-k)-RI-OR2-TAT, using a GE TRACERlab FX-FN. RI-OR2-TAT is a brain-penetrant, retro-inverso peptide that binds to amyloid species associated with Alzheimer's Disease. Radiolabelled (Aoa-k)-RI-OR2-TAT was reproducibly synthesised and the product of the reaction with FPCA has been fully characterised. In-vivo biodistribution of ["1"8F]RI-OR2-TAT has been measured in Wistar rats.

False-positive uptake on 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) in oncological imaging

International Nuclear Information System (INIS)

Culverwell, A.D.; Scarsbrook, A.F.; Chowdhury, F.U.

2011-01-01

With the increasing utilization of integrated positron-emission tomography/computed tomography (PET/CT) using the glucose analogue 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG) in oncological imaging, it is important for radiologists and nuclear medicine physicians to be aware that FDG uptake is not specific for malignancy, as many different physiological variants and benign pathological conditions can also exhibit increased glucose metabolism. Such false-positive FDG uptake often arises outside the area of primary interest and may mimic malignant disease, thereby confounding accurate interpretation of PET/CT studies. With the use of illustrative clinical cases, this article will provide a systematic overview of potential interpretative pitfalls and illustrate how such unexpected findings can be appropriately evaluated.

A Multi-tracer Dopaminergic PET Study of Young-Onset Parkinsonian Patients With and Without Parkin Gene Mutations

International Nuclear Information System (INIS)

Ribeiro, M.J.; Thobois, St.; Broussolle, E.; Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A.; Lohmann, E.; Agid, Y.; Brice, A.; Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A.; Tezenas du Montcel, S.; Tezenas du Montcel, S.; Pelissolo, A.; Dubois, B.; Mallet, L.; Pollak, P.; Agid, Y.; Brice, A.; Remy, Ph.; Remy, Ph.

2009-01-01

The impact of parkin gene mutations on nigrostriatal dopaminergic degeneration is not well established. The purpose of this study was to characterize by PET using 18 F-fluoro-L-3, 4- dihydroxyphenylalanine ( 18 F-fluoro-L-DOPA), 11 C-PE2I, and 11 C-raclopride the pattern of dopaminergic lesions in young-onset Parkinson disease (YOPD) patients with or without mutations of the parkin gene and to correlate the clinical and neuro-psychologic characteristics of these patients with PET results. Methods: A total of 35 YOPD patients were enrolled (16 with parkin mutation, 19 without). The uptake constant (K i ) of 18 F-fluoro- L-DOPA and the binding potential (BP) of 11 C-PE2I (BPDAT) and of 11 C-raclopride (BPD2) were calculated in the striatum. Comparisons were made between the 2 groups of YOPD and between controls and patients. For each radiotracer, parametric images were obtained, and statistical parametric mapping (SPM) analysis using a voxel-by-voxel statistical t test was performed. Correlations between the cognitive and motor status and PET results were analyzed. Results: In YOPD patients, 18 F-fluoro-L-DOPA K i values were reduced to 68% (caudate) and 40% (putamen) of normal values (P ≤ 0.0001). This decrease was symmetric and comparable for non-parkin and parkin patients. No correlation was found between the K i values and cognitive or motor status. 11 C-PE2I BPDAT values in YOPD patients were decreased to 56% (caudate) and 41% (putamen) of normal values (P ≤ 0.0001) and did not differ between the 2 YOPD populations. The mean 11 C-raclopride BPD2 values were reduced to 72% (caudate) and 84% (putamen) of the normal values (P ≤ 0.02) and did not differ between non-parkin and parkin patients. SPM analyses showed in patients an additional decrease of 11 C-raclopride in the frontal cortex and a decrease of 18 F-fluoro-L-DOPA and 11 C-PE2I uptake in the substantia nigra bilaterally (P ≤ 0.05, false-discovery rate-corrected). Conclusion: Carriers of parkin

Novel radiosynthesis of PET HSV-tk gene reporter probes [18F]FHPG and [18F]FHBG employing dual Sep-Pak SPE techniques.

Science.gov (United States)

Wang, Ji-Quan; Zheng, Qi-Huang; Fei, Xiangshu; Mock, Bruce H; Hutchins, Gary D

2003-11-17

Positron emission tomography (PET) herpes simplex virus thymidine kinase (HSV-tk) gene reporter probes 9-[(3-[(18)F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([(18)F]FHPG) and 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine ([(18)F]FHBG) were prepared by nucleophilic substitution of the appropriate tosylated precursors with [(18)F]KF/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified dual Silica Sep-Pak solid-phase extraction (SPE) method in 15-30% radiochemical yield.

Production of PET radiopharmaceutical 18F-FDG using synthesizer automatic module

International Nuclear Information System (INIS)

Purwoko; Chairuman; Adang Hardi Gunawan; Yayan Tahyan; Eny Lestari; Sri Aguswarini Lestiyowati; Karyadi; Sri Bagiawati

2010-01-01

Radiopharmaceutical 2-( 18 F)Fluoro-2-Deoxy-D-Glucose or 18 F(FDG) is an important PET (Positron Emission Tomography) radiopharmaceutical for tumour imaging. In the PET technique glucose metabolism in tumour tissues can be determined quantitatively and used for diagnosis staging and monitoring of treatment tumour or cancer disease in medical oncology. The production of 2-( 18 F)Fluoro-2-Deoxy-D-Glucose 18 F-FDG using compact automated system module TRACERlab MX has been carried out. The modular setup of the apparatus permits reliable for routine synthesis of radiopharmaceuticals 18 F-FDG based on kriptofix mediated nucleophilic fluorination to mannose triflate precursor. Radiochemical yield of 18 F-FDG was 53.895 % (decay time uncorrected) in 40 minutes. The product showed that the colorless and clear solution at pH:6, sterile and pirogen free, kriptofix impurities was low and radiochemical purity was 99.595%. (author)

Discriminative sensing of DOPA enantiomers by cyclodextrin anchored graphene nanohybrids.

Science.gov (United States)

Ates, Salih; Zor, Erhan; Akin, Ilker; Bingol, Haluk; Alpaydin, Sabri; Akgemci, Emine G

2017-06-01

Discriminative sensing of chiral species with a convenient and robust system is a challenge in chemistry, pharmaceutics and particularly in biomedical science. Advanced nanohybrid materials for discrimination of these biologically active molecules can be developed by combination of individual obvious advantages of different molecular scaffolds. Herein, we report on the comparison of the performance of cyclodextrin functionalized graphene derivatives (x-CD/rGO, x: α-, β-, γ-) for discrimination of DOPA enantiomers. Within this respect, electrochemical measurements were conducted and the experimental results were compared to molecular docking method. Thanks to cavity size of γ-CD and the unique properties of graphene, rGO/γ-CD nanohybrid is capable of selective recognition of DOPA enantiomers. Limit of detection (LOD) value and sensitivity were determined as 15.9 μM and 0.2525 μA μM -1 for D-DOPA, and 14.9 μM and 0.6894 μA μM -1 for L-DOPA. Copyright © 2017 Elsevier B.V. All rights reserved.

Biodistribution and breast tumor uptake of 16α-[18F]-fluoro-17β-estradiol in rat

International Nuclear Information System (INIS)

Sasaki, Masayuki; Fukumura, Toshimitsu; Kuwabara, Yasuo; Yoshida, Tsuyoshi; Nakagawa, Makoto; Ichiya, Yuichi; Masuda, Kouji

2000-01-01

To evaluate the usefulness of 16α-[ 18 F]-fluoro-17β-estradiol (FES) for the assessment of estrogen receptor (ER), we examined the tissue distribution and kinetics of FES in immature female Sprague-Dawley rats and then examined FES uptake in rat breast tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA). The FES uptake by the uterus, an ER-rich tissue, was highly selective and it was 3.34±0.79%ID/g at 60 minutes and 1.57±0.57%ID/g at 120 minutes after injection. The FES uptakes in ER-negative tissues were 0.12±0.05%ID/g or less and 0.05±0.03%ID/g or less, respectively. Coadministration of unlabeled β-estradiol showed marked depression of uterine FES uptake. The FES uptake by rat breast tumors was 0.14±0.06%ID/g at 60 min and 0.12±0.09%ID/g at 120 min. The FES uptake by rat breast tumors correlated with the ER concentration (r=0.45, p<0.05). In conclusion, these results suggest that the FES uptake by tissue is mainly ER mediated and FES is thus useful for detecting ER positive breast tumors. (author)

Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

International Nuclear Information System (INIS)

Kienast, Thorsten; Rapp, Michael; Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias; Wrase, Jana; Heinz, Andreas; Braus, Dieter F.; Smolka, Michael N.; Mann, Karl; Roesch, Frank; Cumming, Paul; Gruender, Gerhard; Bartenstein, Peter

2008-01-01

Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [ 18 F]DOPA for measurements of dopamine synthesis capacity and [ 18 F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [ 18 F]DOPA net influx constant K in app /[ 18 F]DMFP-binding potential (BP N D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

Excessive sensitivity to uncertain visual input in L-dopa induced dyskinesias in Parkinson’s disease: further implications for cerebellar involvement

Directory of Open Access Journals (Sweden)

James eStevenson

2014-02-01

Full Text Available When faced with visual uncertainty during motor performance, humans rely more on predictive forward models and proprioception and attribute lesser importance to the ambiguous visual feedback. Though disrupted predictive control is typical of patients with cerebellar disease, sensorimotor deficits associated with the involuntary and often unconscious nature of L-dopa-induced dyskinesias in Parkinson’s disease (PD suggests dyskinetic subjects may also demonstrate impaired predictive motor control. Methods: We investigated the motor performance of 9 dyskinetic and 10 non-dyskinetic PD subjects on and off L-dopa, and of 10 age-matched control subjects, during a large-amplitude, overlearned, visually-guided tracking task. Ambiguous visual feedback was introduced by adding ‘jitter’ to a moving target that followed a Lissajous pattern. Root mean square (RMS tracking error was calculated, and ANOVA, robust multivariate linear regression and linear dynamical system analyses were used to determine the contribution of speed and ambiguity to tracking performance. Results: Increasing target ambiguity and speed contributed significantly more to the RMS error of dyskinetic subjects off medication. L-dopa improved the RMS tracking performance of both PD groups. At higher speeds, controls and PDs without dyskinesia were able to effectively de-weight ambiguous visual information. Conclusions: PDs’ visually-guided motor performance degrades with visual jitter and speed of movement to a greater degree compared to age-matched controls. However, there are fundamental differences in PDs with and without dyskinesia: subjects without dyskinesia are generally slow, and less responsive to dynamic changes in motor task requirements but, PDs with dyskinesia there was a trade-off between overall performance and inappropriate reliance on ambiguous visual feedback. This is likely associated with functional changes in posterior parietal-ponto-cerebellar pathways.

Comparison of Positron Emission Tomography Using 2-[18F]-fluoro-2-deoxy-D-glucose and 3-deoxy-3-[18F]-fluorothymidine in Lung Cancer Imaging

Science.gov (United States)

Wang, Fu-Li; Tan, Ye-Ying; Gu, Xiang-Min; Li, Tian-Ran; Lu, Guang-Ming; Liu, Gang; Huo, Tian-Long

2016-01-01

Background: The detection of solitary pulmonary nodules (SPNs) that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography (CT) imaging results remains a significant challenge. The 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[18F]-fluorothymidine (18F-FLT) in lung cancer PET/CT imaging. Methods: The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established (n = 12), and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values (SUVs), and Ki-67 proliferation marker expression were investigated. Results: The cell-tracer binding ratio for the A549 cells using the 18F-FDG was greater than the ratio using 18F-FLT (P < 0.05). The Ki-67 expression showed a significant positive correlation with the 18F-FLT binding ratio (r = 0.824, P < 0.01). The tumor-to-nontumor uptake ratio of 18F-FDG imaging in xenografts was higher than that of 18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of 18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of 18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of 18F-FDG and 18F-FLT (r = 0.658, P < 0.05 and r = 0.724, P < 0.01, respectively). Conclusions: The 18F-FDG uptake ratio is higher than that of 18F-FLT in A549 cells at the cellular level. 18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor

In vitro and in vivo investigation of natural compounds from seed extract of Mucuna pruriens lacking l-DOPA for the treatment of erectile dysfunction.

Science.gov (United States)

Duangnin, Natthachai; Phitak, Thanyaluck; Pothacharoen, Peraphan; Kongtawelert, Prachya

2017-03-01

To investigate the biological effects of the Mucuna pruriens (M. pruriens) seed extracts that lacked l-DOPA, which was formerly reported as the active ingredient, on erectile dysfunction (ED) both in vitro and in vivo. Seed of M. pruriens plant that cultivated in Mae Taeng District, Chiang Mai Province, Thailand, was collected. Component of its seeds were extracted and isolated into 2 fractions using methanol, polar and nonpolar. Each fraction was investigated for phytochemicals using gas chromatography and mass spectroscopy and was screened for biological activity in vitro using three different cell lines. The most biological active fraction was used to treat both streptozotocin (STZ)-induced diabetes mellitus-erectile dysfunction (DM-ED) male Wistar rats and normal rats (n = 6 per groups) to compare the effect on sexual behavior parameters, including number of intromission, mounting and ejaculation, with that of rats given Sildenafil by individually pairing with their female counterparts. Penile tissues and serums were collected to determine histological structure, related gene expression and biomolecules. The phytochemicals of the polar fraction were possibly catechol and its derivatives plus polyphenols, whereas the nonpolar fraction consisted of lipid derivatives. l-DOPA was not detected in either of the extracts. The polar fraction was able to up-regulate the expression of ED-related genes including eNOS and nNOS in vitro which subsequently promotes nitric oxide production and maintains intracellular cyclic guanosine monophosphate levels. When administrated to DM-ED rats, the polar extract significantly improved all sexual behavior parameters in DM-ED rats compared to untreated group (18.3 ± 1.8 to 10.8 ± 2.9 for intromission, 9.8 ± 2.2 to 5.7 ± 1.3 for mounting, and 1.8 ± 0.6 to 0.2 ± 0.4 for ejaculation). That effect might due to the ability of the extract to stimulate the expression of eNOS and nNOS which results in nitric oxide

Regional cerebral blood flow measurement with intravenous [15O]water bolus and [18F]fluoromethane inhalation

International Nuclear Information System (INIS)

Herholz, K.; Pietrzyk, U.; Wienhard, K.; Hebold, I.; Pawlik, G.; Wagner, R.; Holthoff, V.; Klinkhammer, P.; Heiss, W.D.

1989-01-01

In 20 patients with ischemic cerebrovascular disease, classic migraine, or angiomas, we compared paired dynamic positron emission tomographic measurements of regional cerebral blood flow using both [ 15 O]water and [ 18 F]fluoromethane as tracers. Cerebral blood flow was also determined according to the autoradiographic technique with a bolus injection of [ 15 O]water. There were reasonable overall correlations between dynamic [ 15 O]water and [ 18 F]fluoromethane values for cerebral blood flow (r = 0.82) and between dynamic and autoradiographic [ 15 O]water values for cerebral blood flow (r = 0.83). We found a close correspondence between abnormal pathologic findings and visually evaluated cerebral blood flow tomograms obtained with the two tracers. On average, dynamic [ 15 O]water cerebral blood flow was 6% lower than that measured with [ 18 F]fluoromethane. There also was a general trend toward a greater underestimation with [ 15 O]water in high-flow areas, particularly in hyperemic areas, probably due to incomplete first-pass extraction of [ 15 O]water. Underestimation was not detected in low-flow areas or in the cerebellum. Absolute cerebral blood flow values were less closely correlated between tracers and techniques than cerebral blood flow patterns. The variability of the relation between absolute flow values was probably caused by confounding effects of the variation in the circulatory delay time. The autoradiographic technique was most sensitive to this type error

Infective endocarditis detected by 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography in a patient with occult infection

Directory of Open Access Journals (Sweden)

Chia-Lu Yeh

2011-11-01

Full Text Available Integrated 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT has been clinically used to detect infectious lesions. We present a case with pyrexia and bacteremia of unknown origin. Whole body FDG PET/CT was arranged to look for an occult source of infection and it revealed a focal lesion with increased FDG uptake in the mitral valve area. Under suspicion of infective endocarditis, transthoracic echocardiography was repeated and then the presence of linear vegetation over the calcified mitral annulus was confirmed. Ultimately, definite infective endocarditis was diagnosed according to the Duke criteria. The patient recovered after the antibiotic therapy. In our case, FDG PET/CT can help to localize the exact site of occult infection, thereby guiding additional testing and facilitating timely definitive diagnosis and therapy.

Sequence of the amino-terminal region of rat liver ribosomal proteins S4, S6, S8, L6, L7a, L18, L27, L30, L37, L37a, and L39.

Science.gov (United States)

Wittmann-Liebold, B; Geissler, A W; Lin, A; Wool, I G

1979-01-01

The sequence of the amino-terminal region of eleven rat liver ribosomal proteins--S4, S6, S8, L6, L7a, L18, L27, L30, L37a, and L39--was determined. The analysis confirmed the homogeneity of the proteins and suggests that they are unique, since no extensive common sequences were found. The N-terminal regions of the rat liver proteins were compared with amino acid sequences in Saccharomyces cerevisiae and in Escherichia coli ribosomal proteins. It seems likely that the proteins L37 from rat liver and Y55 from yeast ribosomes are homologous. It is possible that rat liver L7a or L37a or both are related to S cerevisiae Y44, although the similar sequences are at the amino-terminus of the rat liver proteins and in an internal region of Y44. A number of similarities in the sequences of rat liver and E coli ribosomal proteins have been found; however, it is not yet possible to say whether they connote a common ancestry.

Loss of metabolites from monkey striatum during PET with FDOPA

DEFF Research Database (Denmark)

Cumming, P; Munk, O L; Doudet, D

2001-01-01

constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

The Parkinson's disease death rate: carbidopa and vitamin B6

Directory of Open Access Journals (Sweden)

Hinz M

2014-10-01

Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole31Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3Cole Center for Healing, Cincinnati, OH, USAAbstract: The only indication for carbidopa and benserazide is the management of L-3,4-dihydroxyphenylalanine (L-dopa-induced nausea. Both drugs irreversibly bind to and permanently deactivate pyridoxal 5'-phosphate (PLP, the active form of vitamin B6, and PLP-dependent enzymes. PLP is required for the function of over 300 enzymes and proteins. Virtually every major system in the body is impacted directly or indirectly by PLP. The administration of carbidopa and benserazide potentially induces a nutritional catastrophe. During the first 15 years of prescribing L-dopa, a decreasing Parkinson's disease death rate was observed. Then, in 1976, 1 year after US Food and Drug Administration approved the original L-dopa/carbidopa combination drug, the Parkinson's disease death rate started increasing. This trend has continued to the present, for 38 years and counting. The previous literature documents this increasing death rate, but no hypothesis has been offered concerning this trend. Carbidopa is postulated to contribute to the increasing Parkinson's disease death rate and to the classification of Parkinson's as a progressive neurodegenerative disease. It may contribute to L-dopa tachyphylaxis.Keywords: L-dopa, levodopa, vitamin B6, pyridoxal 5'-phosphate

Is a volume of 3.6 mL better than 1.8 mL for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis?

Science.gov (United States)

Fowler, Sara; Reader, Al

2013-08-01

The purpose of this retrospective study was to determine the success of the inferior alveolar nerve (IAN) block using either 3.6 mL or 1.8 mL 2% lidocaine with 1:100,000 epinephrine in patients presenting with symptomatic irreversible pulpitis. As part of 7 previously published studies, 319 emergency patients presenting with symptomatic irreversible pulpitis received either a 1.8-mL volume or 3.6-mL volume of 2% lidocaine with 1:100,000 epinephrine in an IAN block. One hundred ninety patients received a 1.8-mL volume, and 129 received a 3.6-mL volume. Endodontic emergency treatment was completed on each subject. Success was defined as the ability to access and instrument the tooth without pain (visual analog scale score of 0) or mild pain (VAS rating ≤54 mm). Success of the 1.8-mL volume was 28%, and for the 3.6-mL volume it was 39%. There was no statistically significant difference between the 2 volumes. In conclusion, for patients presenting with irreversible pulpitis, success was not significantly different between a 3.6-mL volume and a 1.8-mL volume of 2% lidocaine with 1:100,000 epinephrine. The success rates (28%-39%) with either volume were not high enough to ensure complete pulpal anesthesia. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The protective effect of SCR(15-18) on cerebral ischemia-reperfusion injury.

Science.gov (United States)

Li, Shu; Xian, Jinhong; He, Li; Luo, Xue; Tan, Bing; Yang, Yongtao; Liu, Gaoke; Wang, Zhengqing

2011-10-01

Soluble complement receptor type 1 (sCR1), a potent inhibitor of complement activation, has been shown to protect brain cells against cerebral ischemic/reperfusion (CI/R) injury due to its decay-accelerating activity for C3/C5 convertase and co-factor activity for C3b/C4b degradation. However, the effect of short consensus repeats (SCRs) 15-18, one of active domains of sCR1 with high C3b/C4b degradability, has not been demonstrated. Here, we investigated the protective effect of recombinant SCR(15-18) protein in middle cerebral artery occlusion (MCAO)-induced focal CI/R injury. Recombinant SCR(15-18) protein was successfully expressed in Escherichia coli and refolded to its optimal bioactivity. Seventy-five Sprague-Dawley rats were randomly assigned into three groups: sham-operated group, CI/R group, and SCR(15-18)+CI/R group pretreated with 20 mg/kg SCR(15-18) protein. After 2 hours of MCAO and subsequent 24 hours of reperfusion, rats were evaluated for neurological deficits and cerebral infarction. Polymorphonuclear leukocyte accumulation, C3b deposition, and morphological changes in cerebral tissue were also estimated. SCR(15-18) pretreatment induced a 20% reduction of infarct size and an improvement of neurological function with 22·2% decrease of neurological deficit scores. Inhibition of cerebral neutrophils infiltration by SCR(15-18) was indicated from the reduction of myeloperoxidase activity in SCR(15-18)+CI/R rats. Decreased C3b deposition and improved morphological changes were also found in cerebral tissue of SCR(15-18)-treated rats. Our studies suggest a definitive moderately protective effect of SCR(15-18) against CI/R damage and provide preclinical experimental evidence supporting the possibility of using it as a small anti-complement therapeutic agent for CI/R injury therapy.

l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease

DEFF Research Database (Denmark)

Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

2017-01-01

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l......-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible...... cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease....

Motivational Disturbances and Effects of L-dopa Administration in Neurofibromatosis-1 Model Mice

Science.gov (United States)

Wozniak, David F.; Diggs-Andrews, Kelly A.; Conyers, Sara; Yuede, Carla M.; Dearborn, Joshua T.; Brown, Jacquelyn A.; Tokuda, Kazuhiro; Izumi, Yukitoshi; Zorumski, Charles F.; Gutmann, David H.

2013-01-01

Children with neurofibromatosis type 1 (NF1) frequently have cognitive and behavioral deficits. Some of these deficits have been successfully modeled in Nf1 genetically-engineered mice that develop optic gliomas (Nf1 OPG mice). In the current study, we show that abnormal motivational influences affect the behavior of Nf1 OPG mice, particularly with regard to their response to novel environmental stimuli. For example, Nf1 OPG mice made fewer spontaneous alternations in a Y-maze and fewer arm entries relative to WT controls. However, analysis of normalized alternation data demonstrated that these differences were not due to a spatial working memory deficit. Other reported behavioral results (e.g., open-field test, below) suggest that differential responses to novelty and/or other motivational influences may be more important determinants of these kinds of behavior than simple differences in locomotor activity/spontaneous movements. Importantly, normal long-term depression was observed in hippocampal slices from Nf1 OPG mice. Results from elevated plus maze testing showed that differences in exploratory activity between Nf1 OPG and WT control mice may be dependent on the environmental context (e.g., threatening or non-threatening) under which exploration is being measured. Nf1 OPG mice also exhibited decreased exploratory hole poking in a novel holeboard and showed abnormal olfactory preferences, although L-dopa (50 mg/kg) administration resolved the abnormal olfactory preference behaviors. Nf1 OPG mice displayed an attenuated response to a novel open field in terms of decreased ambulatory activity and rearing but only during the first 10 min of the session. Importantly, Nf1 OPG mice demonstrated investigative rearing deficits with regard to a novel hanging object suspended on one side of the field which were not rescued by L-dopa administration. Collectively, our results provide new data important for evaluating therapeutic treatments aimed at ameliorating NF1

Motivational disturbances and effects of L-dopa administration in neurofibromatosis-1 model mice.

Directory of Open Access Journals (Sweden)

David F Wozniak

Full Text Available Children with neurofibromatosis type 1 (NF1 frequently have cognitive and behavioral deficits. Some of these deficits have been successfully modeled in Nf1 genetically-engineered mice that develop optic gliomas (Nf1 OPG mice. In the current study, we show that abnormal motivational influences affect the behavior of Nf1 OPG mice, particularly with regard to their response to novel environmental stimuli. For example, Nf1 OPG mice made fewer spontaneous alternations in a Y-maze and fewer arm entries relative to WT controls. However, analysis of normalized alternation data demonstrated that these differences were not due to a spatial working memory deficit. Other reported behavioral results (e.g., open-field test, below suggest that differential responses to novelty and/or other motivational influences may be more important determinants of these kinds of behavior than simple differences in locomotor activity/spontaneous movements. Importantly, normal long-term depression was observed in hippocampal slices from Nf1 OPG mice. Results from elevated plus maze testing showed that differences in exploratory activity between Nf1 OPG and WT control mice may be dependent on the environmental context (e.g., threatening or non-threatening under which exploration is being measured. Nf1 OPG mice also exhibited decreased exploratory hole poking in a novel holeboard and showed abnormal olfactory preferences, although L-dopa (50 mg/kg administration resolved the abnormal olfactory preference behaviors. Nf1 OPG mice displayed an attenuated response to a novel open field in terms of decreased ambulatory activity and rearing but only during the first 10 min of the session. Importantly, Nf1 OPG mice demonstrated investigative rearing deficits with regard to a novel hanging object suspended on one side of the field which were not rescued by L-dopa administration. Collectively, our results provide new data important for evaluating therapeutic treatments aimed at

PET/CT comparing 68Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

International Nuclear Information System (INIS)

Janssen, Ingo; Chen, Clara C.; Millo, Corina M.; Herscovitch, Peter; Ling, Alexander; Taieb, David; Lin, Frank I.; Adams, Karen T.; Wolf, Katherine I.; Pacak, Karel; Fojo, Antonio T.; Buchmann, Inga; Kebebew, Electron

2016-01-01

Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). 68 Ga-DOTA(0)-Tyr(3)-octreotate ( 68 Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of 68 Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. This prospective study included 22 patients (15 men, 7 women; aged 50.0 ± 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent 68 Ga-DOTATATE, 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) PET/CT scan and only 11 patients underwent an additional 18 F-fluorodopamine ( 18 F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. 68 Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). 18 F-FDG PET/CT, 18 F-FDOPA PET/CT, 18 F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p < 0.01), 74.8 % (CI 69.0 - 79.9 %; p < 0.01), 77.7 % (CI 71.5 - 82.8 %; p < 0.01), and 81.6 % (CI 77.8 - 84.8 %; p < 0.01), respectively. The results of this study demonstrate the superiority of 68 Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality. (orig.)

A Multi-tracer Dopaminergic PET Study of Young-Onset Parkinsonian Patients With and Without Parkin Gene Mutations

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, M.J. [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Thobois, St.; Broussolle, E. [University of Lyon, Hospices Civils de Lyon, Neurological Hospital, Lyon (France); Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A. [INSERM, Paris (France); Lohmann, E.; Agid, Y.; Brice, A. [Department of the Nervous System Disorders, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A. [UPMC University of Paris, Paris (France); Tezenas du Montcel, S. [Unit of de Biostatistics and Medical Information and Unit of Medical Research, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Tezenas du Montcel, S. [Modelisation in Clinical Research, UPMC University of Paris, Paris (France); Pelissolo, A. [Department of Psychiatry, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Dubois, B. [Centre de Reference sur la Maladie de Pick, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Mallet, L. [Behaviour, Emotion and Basal Ganglia, Center of Clinical Investigation, INSERM Avenir Group, Paris (France); Pollak, P. [Department of Clinical and Biological Neurosciences, University Hospital of Grenoble, Grenoble (France); Agid, Y. [Clinical Investigation Center, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Brice, A. [Department of Genetics and Cytogenetics, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Remy, Ph. [CEA, I2BM, MIRCEN, URA CEA-CNRS 2210, Orsay (France); Remy, Ph. [CHU Henri Mondor, AP-HP and Faculte de Medecine Paris 12, Creteil (France)

2009-07-01

The impact of parkin gene mutations on nigrostriatal dopaminergic degeneration is not well established. The purpose of this study was to characterize by PET using {sup 18}F-fluoro-L-3, 4- dihydroxyphenylalanine ({sup 18}F-fluoro-L-DOPA), {sup 11}C-PE2I, and {sup 11}C-raclopride the pattern of dopaminergic lesions in young-onset Parkinson disease (YOPD) patients with or without mutations of the parkin gene and to correlate the clinical and neuro-psychologic characteristics of these patients with PET results. Methods: A total of 35 YOPD patients were enrolled (16 with parkin mutation, 19 without). The uptake constant (K{sub i}) of {sup 18}F-fluoro- L-DOPA and the binding potential (BP) of {sup 11}C-PE2I (BPDAT) and of {sup 11}C-raclopride (BPD2) were calculated in the striatum. Comparisons were made between the 2 groups of YOPD and between controls and patients. For each radiotracer, parametric images were obtained, and statistical parametric mapping (SPM) analysis using a voxel-by-voxel statistical t test was performed. Correlations between the cognitive and motor status and PET results were analyzed. Results: In YOPD patients, {sup 18}F-fluoro-L-DOPA K{sub i} values were reduced to 68% (caudate) and 40% (putamen) of normal values (P {<=} 0.0001). This decrease was symmetric and comparable for non-parkin and parkin patients. No correlation was found between the K{sub i} values and cognitive or motor status. {sup 11}C-PE2I BPDAT values in YOPD patients were decreased to 56% (caudate) and 41% (putamen) of normal values (P {<=} 0.0001) and did not differ between the 2 YOPD populations. The mean {sup 11}C-raclopride BPD2 values were reduced to 72% (caudate) and 84% (putamen) of the normal values (P {<=} 0.02) and did not differ between non-parkin and parkin patients. SPM analyses showed in patients an additional decrease of {sup 11}C-raclopride in the frontal cortex and a decrease of {sup 18}F-fluoro-L-DOPA and {sup 11}C-PE2I uptake in the substantia nigra bilaterally

Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

Energy Technology Data Exchange (ETDEWEB)

Kienast, Thorsten; Rapp, Michael [Charite Campus Mitte, Department of Psychiatry and Psychotherapy of the Charite University Medical Center, Berlin (Germany); Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias [University of Mainz, Department of Nuclear Medicine, Mainz (Germany); Wrase, Jana; Heinz, Andreas [Charite Campus Mitte, Department of Psychiatry and Psychotherapy of the Charite University Medical Center, Berlin (Germany); Central Institute of Mental Health, Mannheim (Germany); Braus, Dieter F. [University of Hamburg, Neuroimage Nord, Department of Psychiatry, Hamburg (Germany); Smolka, Michael N.; Mann, Karl [Central Institute of Mental Health, Mannheim (Germany); Roesch, Frank [University of Mainz, Institute of Nuclear Chemistry, Mainz (Germany); Cumming, Paul [PET Center and Center for Functionally Integrative Neuroscience, Aarhus (Denmark); Gruender, Gerhard [Aachen University Medical Center, Department of Psychiatry of the RWTH, Mainz (Germany); Bartenstein, Peter [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany)

2008-06-15

Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [{sup 18}F]DOPA for measurements of dopamine synthesis capacity and [{sup 18}F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [{sup 18}F]DOPA net influx constant K{sub in}{sup app} /[{sup 18}F]DMFP-binding potential (BP{sub N}D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

Utilization of fluoro dopa in nuclear medicine method for determination of radiochemical purity: study of irradiation during the manipulation; Utilisation de la FDOPA dans un service de medecine nucleaire: mise au point d'une methode de controle de purete radiochimique, etude de poste sur l'irradiation de l'operateur lors de la manipulation

Energy Technology Data Exchange (ETDEWEB)

Bizien, V

2007-10-15

As a first step is a bibliographic reminder done on the use of two main fluorine molecules, FDG and F DOPA. The objective of the work then acted to develop a chromatographic method for determining the radiochemical purity of F DOPA response to the alteration of its stability after neutralization. Finally, the optimization of a technique of TLC will determine a period of stability in order to offset the risks that may delay examinations (breakdowns of cameras). The preparation of product requires handling, a study of post will then determine radiation doses on ends of members and on the whole-body when preparing the F DOPA. (N.C.)

L-dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer.

Science.gov (United States)

Koutalellis, Georgios; Stravodimos, Konstantinos; Avgeris, Margaritis; Mavridis, Konstantinos; Scorilas, Andreas; Lazaris, Andreas; Constantinides, Constantinos

2012-09-01

What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL. DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination

Synthesis and preliminary evaluation of 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl) guanine ([{sup 18}F]FHBG) in HSV1-tk gene transduced hepatoma cell

Energy Technology Data Exchange (ETDEWEB)

Moon, Byung Seok; Lee, Tae Sup [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Myoung Keun [Yonsei University, Wonju (Korea, Republic of)] (and others)

2006-08-15

The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl) guanine ([{sup 18}F]FHBG) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with K[{sup 18}F]/K2.2.2. in acetonitrile using N2-monomethoxytrityl-9-[4-(tosly)-3-monomethoxytritylmethylbutl] guanine as a precursor, followed by deprotection with 1 N HCI. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of [{sup 18}F]FHBG were performed, and was analyzed correlation between [{sup 18}F]FHBG uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor beating Balb/c-nude mouse model. [{sup 18}F]FHBG was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiochemical yield was about 20-25% (corrected for decay), radiochemical purity was > 95% and specific activity was around > 55.5 GBq/ {mu} mol. Specific accumulation of [{sup 18}F]FHBG was observed in HSV1-tk gene transduced MCA-tk cells but not MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked [{sup 18}F]FHBG was retained inside of cells. The uptake of [{sup 18}F]FHBG was showed a highly significant linear correlation (R{sup 2} = 0.995) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. [{sup 18}F]FHBG appears