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1.
Auton Neurosci ; 237: 102910, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34801829

RESUMEN

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder. We report a 59-year-old man who presented with progressive encephalomyelitis causing diplopia, bulbar palsy, severe dysautonomia, followed by stiffness and myoclonic cluster. Laboratory tests showed mild pleocytosis, with markedly elevated plasma levels of norepinephrine, epinephrine, and arginine vasopressin. Glycine-receptor antibodies were identified in both serum and CSF. Despite a poor response to methylprednisolone, immunoglobulins, and plasma exchange, α-blocker stabilized dysautonomia. Dysautonomia is presumed to be due to antibody-mediated disinhibited sympathetic hyperactivity; however, this case suggests that concomitant use of α-blocker with immunotherapy may ameliorate dysautonomia.


Asunto(s)
Encefalomielitis , Mioclonía , Disautonomías Primarias , Encefalomielitis/complicaciones , Encefalomielitis/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Rigidez Muscular , Mioclonía/tratamiento farmacológico , Receptores de Glicina
2.
Toxins (Basel) ; 11(6)2019 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-31234410

RESUMEN

Cyanobacteria have been shown to produce a number of bioactive compounds, including toxins. Some bioactive compounds obtained from a marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) have been recognized as drug leads; one of these compounds is aplysiatoxin. We have isolated various aplysiatoxin derivatives from a M. producens sample obtained from the Okinawan coastal area. The frozen sample was extracted with organic solvents. The ethyl acetate layer was obtained from the crude extracts via liquid-liquid partitioning, then separated by HPLC using a reversed-phase column. Finally, 1.1 mg of the compound was isolated. The chemical structure of the isolated compound was elucidated with spectroscopic methods, using HR-MS and 1D and 2D NMR techniques, and was revealed to be oscillatoxin I, a new member of the aplysiatoxin family. Oscillatoxin I showed cytotoxicity against the L1210 mouse lymphoma cell line and diatom growth-inhibition activity against the marine diatom Nitzschia amabilis.


Asunto(s)
Toxinas Bacterianas/aislamiento & purificación , Cianobacterias , Toxinas de Lyngbya/aislamiento & purificación , Animales , Toxinas Bacterianas/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diatomeas/efectos de los fármacos , Diatomeas/crecimiento & desarrollo , Toxinas de Lyngbya/toxicidad , Ratones
3.
Kyobu Geka ; 69(7): 545-7, 2016 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-27365069

RESUMEN

A 58-year-old female presented to our hospital with recurrence of chest pain. She had undergone coronary intervention using biolimus-eluting-stent for total occlusion of the left anterior descending artery(LAD) 3 years before. Since then in-stent restenosis had repeated 4 times in 3 years. In the interim, another everolimus-eluting-stent had been placed on the same lesion. The contact metal allergic patch test revealed the existence of allergic response to nickel and cobalt which were the structural components of these stents. She underwent off-pump coronary artery bypass grafting, and these stents were removed. The invasions of macrophages and eosinophils around the stent-s were pathologically proven. One year after surgery she is doing well without angina or allergic symptom. These observations suggested the allergic reaction of the coronary artery against the stents.


Asunto(s)
Cobalto/efectos adversos , Cobalto/inmunología , Puente de Arteria Coronaria Off-Pump , Reestenosis Coronaria/etiología , Reestenosis Coronaria/terapia , Stents Liberadores de Fármacos/efectos adversos , Hipersensibilidad/etiología , Infarto del Miocardio/terapia , Níquel/efectos adversos , Níquel/inmunología , Reestenosis Coronaria/inmunología , Remoción de Dispositivos , Eosinófilos/inmunología , Eosinófilos/patología , Femenino , Humanos , Hipersensibilidad/inmunología , Macrófagos/inmunología , Macrófagos/patología , Persona de Mediana Edad , Insuficiencia del Tratamiento , Resultado del Tratamiento
4.
Biochem Biophys Res Commun ; 454(1): 7-11, 2014 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-25301551

RESUMEN

We herein examined the biological effects of cells treated with (18)F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of (18)F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with two types of (18)F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF). FDG efficiently accumulated in cells, whereas HF did not. To examine the induction of DNA double strand breaks (DSB), we measured the number of foci for 53BP1 that formed at the site of DNA DSB. The results revealed that although radioactivity levels were the same, the induction of 53BP1 foci was stronger in cells treated with (18)F-FDG than in those treated with (18)F-HF. The clonogenic survival of cells was significantly lower with (18)F-FDG than with (18)F-HF. We concluded that the efficient accumulation of (18)F in cells led to stronger biological effects due to more severe cellular lethality via the induction of DNA DSB.


Asunto(s)
Radioisótopos de Flúor/efectos adversos , Radioisótopos de Flúor/farmacocinética , Fluorodesoxiglucosa F18/efectos adversos , Fluorodesoxiglucosa F18/farmacocinética , Tomografía de Emisión de Positrones/efectos adversos , Radiofármacos/efectos adversos , Radiofármacos/farmacocinética , Animales , Células CHO , Supervivencia Celular/efectos de la radiación , Ensayo de Unidades Formadoras de Colonias , Cricetinae , Cricetulus , Roturas del ADN de Doble Cadena , Relación Dosis-Respuesta en la Radiación , Líquido Intracelular/metabolismo , Pruebas de Micronúcleos
5.
Ann Nucl Med ; 28(6): 586-92, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24610680

RESUMEN

OBJECTIVE: We developed a bubble point test kit and investigated the bubble point test of a 0.22-µm membrane filter used for the sterilizing filtration of [(18)F]FDG, [(11)C]MET and [(11)C]PIB. The bubble point test of the Millex-GS vented filter was often difficult due to air leakage from the vented portion of this filter. Therefore, to close the vented portion of this filter simply and reliably, we investigated the use of various materials. METHODS: The bubble point test of the Millex-GS vented filter was performed by closing the vented portion of this filter with various materials, such as vinyl tape, plastic paraffin film (parafilm), urethane elastomer adhesive mat and polyethylene foam cushion tape. Gradually, the plunger inside a syringe filled with air was pushed down to increase the pressure on the pressure gauge and the bubble point test kit. Simultaneously, the pressure when a continuous stream of air bubbles that appeared out of the 0.22-µm membrane filter was measured as the product-wetted bubble point value. Then, the plunger inside a syringe filled with 10 mL of water was pushed down to wash the 0.22-µm membrane filter. As in the case in the above-mentioned method of measuring the product-wetted bubble point, the water-wetted bubble point value was measured. RESULTS: The use of the polyethylene foam cushion tape and a double clip could easily and reliably prevent air leakage from the vented portion of the Millex-GS vented filter. In the bubble point test of [(18)F]FDG, [(11)C]MET and [(11)C]PIB, the product-wetted bubble point values were 382.7 ± 6.9 kPa, 385.4 ± 6.2 kPa and 351.6 ± 7.6 kPa, respectively. The bubble point ratio was used to determine the minimum product-wetted bubble point value. All results of the product-wetted bubble point test were beyond the minimum product-wetted bubble point value (334.4 kPa ([(18)F]FDG), 334.4 kPa ([(11)C]MET) and 310.3 kPa ([(11)C]PIB)). Then, the water-wetted bubble point values were 396.5 ± 8.3 kPa, 395.8 ± 8.3 kPa and 390.3 ± 7.6 kPa, respectively. All results of the water-wetted bubble point test were beyond the filter manufacturer's minimum bubble point specification (344.8 kPa). CONCLUSIONS: The bubble point test technique using the bubble point test kit was practical for routine quality control tests of PET radiopharmaceuticals.


Asunto(s)
Filtración/instrumentación , Tomografía de Emisión de Positrones/instrumentación , Radiofármacos/química , Esterilización/instrumentación , Aire , Compuestos de Anilina , Benzotiazoles/química , Radioisótopos de Carbono/química , Filtración/métodos , Fluorodesoxiglucosa F18/química , Humanos , Ensayo de Materiales , Metionina/química , Tomografía de Emisión de Positrones/métodos , Presión , Control de Calidad , Dosis de Radiación , Esterilización/métodos , Jeringas , Tiazoles , Agua/química
6.
Nucl Med Biol ; 41(1): 17-23, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24183615

RESUMEN

INTRODUCTION: [(11)C]ABP688 is a promising positron emission tomography (PET) ligand for imaging of metabotropic glutamate receptor subtype 5 (mGlu5 receptor). Of the two geometric isomers of ABP688, (E)-ABP688 has a greater affinity towards mGlu5 receptors than (Z)-ABP688. Therefore, a high ratio of E-isomer is required when using [(11)C]ABP688 as a PET probe for imaging and quantification of mGlu5 receptors. The aim of this study was to evaluate the effect (Z)-[(11)C]ABP688 on the synthesis of [(11)C]ABP688 to be used for binding (E)-[(11)C]ABP688 in the brain. METHODS: We synthesized and separated (E)- and (Z)-[(11)C]ABP688 by purification using an improved preparative high-performance liquid chromatography (HPLC) method equipped with a COSMOSIL Cholester column. We performed an in vitro binding assay in rat brain homogenates and PET studies of the rat brains using (E)- and (Z)-[(11)C]ABP688. RESULTS: (E)- and (Z)-[(11)C]ABP688 were successfully obtained with suitable radioactivity for application. In the in vitro assay, the Kd value of (E)-[(11)C]ABP688 (5.7 nmol/L) was higher than that of (Z)-[(11)C]ABP688 (140 nmol/L). In the PET study of the rat brain, high radioactivity after injection of (E)-[(11)C]ABP688 was observed in regions rich in mGlu5 receptors such as the striatum and hippocampus. In contrast, after injection of (Z)-[(11)C]ABP688, radioactivity did not accumulate in the brain. Furthermore, BPND in the striatum and hippocampus was highly correlated (R(2) = 0.99) with the percentage of (E)-[(11)C]ABP688 of the total radioactivity of (E)- and (Z)-[(11)C]ABP688 in the injection. CONCLUSION: We demonstrated that including (Z)-[(11)C]ABP688 in the [(11)C]ABP688 injection can decrease BPND in regions rich in mGlu5 receptors. Routine production of (E)-[(11)C]ABP688 will be helpful for imaging and quantification of mGlu5 receptors in clinical studies.


Asunto(s)
Oximas/química , Oximas/metabolismo , Piridinas/química , Piridinas/metabolismo , Receptor del Glutamato Metabotropico 5/metabolismo , Animales , Encéfalo/metabolismo , Radioisótopos de Carbono , Masculino , Oximas/sangre , Tomografía de Emisión de Positrones , Unión Proteica , Piridinas/sangre , Radioquímica , Ratas , Ratas Sprague-Dawley , Estereoisomerismo , Relación Estructura-Actividad
7.
J Labelled Comp Radiopharm ; 56(5): 295-300, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24285374

RESUMEN

We have developed an ethanol-free formulation method of [(18) F]florbetapir ([(1) (8) F]AV-45) using a commercially available automated JFE multi-purpose synthesizer. We have also evaluated the radiochemical stability in an ethanol-free solution of [(18) F]AV-45 under visible light irradiation and dark conditions by comparison with a conventional 10% ethanol solution of [(18) F]AV-45. [(18) F]AV-45 was obtained with a radiochemical yield of 55.1 ± 2.2% (decay-corrected to end of bombardment), specific activity of 591.6 ± 90.3 GBq/µmol and radiochemical purity of >99% within a total synthesis time of about 73 min. The radiochemical purity of [(18) F]AV-45 formulated by dissolving the ethanol-free solution was found to decrease as a function of the period of exposure to visible light. In contrast, the visible light photolysis could be suppressed by adding 10% ethanol to the formulation or by avoiding exposure to visible light. In the radiosynthesis of [(18) F]AV-45 formulated by dissolving the ethanol-free solution, [(18) F]AV-45 could be obtained with high radiochemical purity and high stability by avoiding exposure to visible light.


Asunto(s)
Compuestos de Anilina/síntesis química , Glicoles de Etileno/síntesis química , Marcaje Isotópico/métodos , Radiofármacos/síntesis química , Compuestos de Anilina/química , Glicoles de Etileno/química , Radiofármacos/química
8.
Circ Cardiovasc Interv ; 4(4): 349-54, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21813403

RESUMEN

BACKGROUND: Although stent fracture (SF) after sirolimus-eluting stent (SES) implantation has been recognized as one of the predisposing factors of in-stent restenosis, it remains uncertain whether SF can increase the risk of major adverse cardiac events (MACE), especially beyond 1 year after SES implantation. The aim of this study was to assess the impact of SF relative to non-SF on 4-year clinical outcomes after treatment with SES of comparable unselected lesions. METHODS AND RESULTS: A total of 874 lesions in 793 patients undergoing SES implantation and subsequent angiography 6 to 9 months after index procedure were analyzed. At 6- to 9-month angiographic follow-up, SF was identified in 70 of 874 lesions (8.0%). In-stent late loss was significantly higher in SF lesions versus non-SF lesions (0.42±0.59 mm versus 0.13±0.49 mm, P<0.001), resulting in a significantly higher in-stent restenosis rate (21.4% versus 4.1%, P<0.001). At 4 years, SF versus non-SF was associated with a significantly higher MACE rate (23.2% versus 12.6%, P=0.014), mainly driven by significantly higher target-lesion revascularization (18.8% versus 10.2%, P=0.029) rate. Adverse effects of SF on clinical outcomes occurred mostly within the first year (17.4% versus 6.6%, P=0.001), with similar MACE rate between 1 and 4 years (5.8% versus 5.9%, P=0.611). No significant differences between SF versus non-SF patients were observed in the cumulative frequency of very late stent thrombosis (2.9% versus 1.4%, P=0.281), death (0% versus 2.1%, P=0.252), or myocardial infarction (5.8% versus 2.9%, P=0.165). CONCLUSIONS: SF of SES was associated with higher MACE rate up to 1 year, mainly driven by higher target-lesion revascularization, whereas no significant association was evident between years 1 and 4.


Asunto(s)
Implantación de Prótesis Vascular , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/etiología , Complicaciones Posoperatorias , Falla de Prótesis/efectos adversos , Anciano , Stents Liberadores de Fármacos/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sirolimus/administración & dosificación , Resultado del Tratamiento
9.
Appl Radiat Isot ; 69(7): 1007-13, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21420304

RESUMEN

The aim of this study was to develop an efficient fully automated synthesis method to achieve a high radiochemical yield of [(18)F]FAZA with a small amount of precursor. A small cartridge containing 25mg of the QMA resin was prepared and evaluated to obtain [(18)F]F(-) in a small quantity of base (K(2)CO(3)), which might allow the use of a small amount of precursor. The labeling and hydrolyzing conditions for [(18)F]FAZA synthesis were also investigated manually. No-carrier-added [(18)F]F(-) was trapped on the small QMA cartridge and eluted with a mixture of Krytofix 222 (2.26 mg, 6.0 µmol) and K(2)CO(3) (0.69 mg, 5.0 µmol) in 70% MeCN (0.4 mL). The automated synthesis of [(18)F]FAZA was optimally performed with a modified NIRS original synthesis system for clinical use, by labeling 2.5mg (5.2 µmol) of the precursor in DMSO (0.4 mL) at 120°C for 10 min, and then by hydrolyzing the (18)F-labeled intermediate with 0.1M NaOH (0.5 mL) at room temperature for 3 min. Using the above condition, the [(18)F]FAZA injection was obtained with a high radiochemical yield of 52.4±5.3% (decay-corrected, n=8) within 50.5±1.5 min.


Asunto(s)
Automatización , Hipoxia de la Célula , Radioisótopos de Flúor , Neoplasias/diagnóstico , Nitroimidazoles , Humanos
10.
EuroIntervention ; 6(3): 388-93, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20884419

RESUMEN

AIMS: To evaluate the frequency, predictors and prognostic significance of elevation in cardiac troponin I (cTnI) after coronary angiography (CAG). METHODS AND RESULTS: A series of 296 consecutive patients with normal pre-procedural cTnI levels and undergoing elective CAG at our centre were prospectively analysed. Positive cTnI elevation was defined as >0.06 ng/ml. Positive cTnI elevation was observed in 44 patients (14.8%), but CK-MB was elevated in only four patients (1.3%) after the procedure. The risk of cTnI elevation was independently associated with left ventricular hypertrophy (odds ratio [OR] 5.52; 95% confidence interval [CI], 2.54 to 12.02; P<0.001), inexperienced operator (OR 10.83; 95% CI, 2.47 to 47.43; P=0.002) and the amount of contrast agent (OR 1.12; 95% CI, 1.03 to 1.23; P=0.009 for each 10 ml increase), whereas it was not associated with the severity of coronary artery disease. At one year, however, postprocedural elevation of cTnI was not associated with an increased risk of death (2.3% vs. 0.8%, P=0.384) or myocardial infarction (2.3% vs. 2.0%, P=0.623). CONCLUSIONS: A minor elevation of cTnI is observed commonly after CAG, which might be associated with left ventricular hypertrophy, operator's experience and the amount of contrast used; however, it does not influence 1-year events rates.


Asunto(s)
Angiografía Coronaria/efectos adversos , Enfermedad Coronaria/diagnóstico por imagen , Creatina Quinasa/sangre , Miocardio/metabolismo , Troponina I/sangre , Biomarcadores/sangre , Enfermedad Coronaria/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
11.
Nucl Med Biol ; 37(1): 67-72, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20122670

RESUMEN

An ultrafast and efficient high-performance liquid chromatographic (LC) method was developed to purify positron emission tomography (PET) radiopharmaceuticals as well as for metabolite analysis of the plasma sample. Chromatographic separation was achieved on a short (60 mm length) semipreparative (10 mm I.D.) column packed with 2.5-mum particles using a mixture of acetonitrile and sodium phosphate buffer as the mobile phase at a flow rate of 8-10 ml/min. Under the optimum conditions, excellent separation of the target PET probe was obtained from chemical/radiochemical impurities or radioactive metabolites with a very short run time of 2 min. This characteristic enabled significant shortening of the purification and evaporation processes in the production of short-lived radiopharmaceuticals and highly sensitive radiometric analysis with good temporal resolution during the metabolism study.


Asunto(s)
Cromatografía Liquida/métodos , Radiofármacos/aislamiento & purificación , Radiofármacos/metabolismo , Radioisótopos de Carbono/química , Cromatografía de Fase Inversa , Humanos , Tomografía de Emisión de Positrones , Purinas/sangre , Purinas/química , Purinas/metabolismo , Radiofármacos/análisis , Factores de Tiempo
12.
Am Heart J ; 158(1): 92-8, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19540397

RESUMEN

BACKGROUND: The presence of chronic kidney disease (CKD) is associated with an increased risk of restenosis and major adverse cardiac events (MACEs) after coronary interventions, especially in patients on hemodialysis (HD). The aim of this study was to assess the impact of varying degrees of renal impairment on angiographic and 2-year clinical outcomes after treatment with sirolimus-eluting stents (SESs). METHODS: A total of 675 lesions of 593 patients treated with SES were analyzed. Patients were classified into 3 groups: 34 patients on HD; 337 patients with estimated glomerular filtration rate > or =60 mL min(-1) 1.73 m(-2) (non-CKD group); and 222 patients who had lower estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2) without HD dependency (CKD group). RESULTS: At angiographic follow-up (201 +/- 73 days), in-segment late loss was markedly higher in the HD group versus the non-CKD and CKD groups (0.68 +/- 1.06 vs 0.11 +/- 0.45 and 0.15 +/- 0.50 mm, respectively, P < .001), resulting in a significantly higher in-segment restenosis rate (40.0% vs 10.4% and 11.5%, respectively, P < .001). At 2 years, HD vs non-CKD and CKD was associated with a significantly higher MACE rate (35.3% vs 10.4% and 12.6%, respectively, P < .001), mainly driven by significantly higher mortality (11.8% vs 0.6% and 2.3%, respectively, P < .001) and target-lesion revascularization (23.5% vs 9.2% and 8.1%, respectively, P = .016) rates. Multivariable analysis revealed that HD was the independent predictor of 2-year MACE (hazard ratio 4.70, 95% CI 2.40-9.20, P < .001). CONCLUSIONS: Although angiographic and clinical outcomes after SES implantation were similarly favorable in non-HD-dependent CKD patients, regardless of renal function, in patients with end-stage CKD requiring HD, frequencies of restenosis and 2-year MACE were markedly higher than in non-HD-dependent patients.


Asunto(s)
Angioplastia Coronaria con Balón , Reestenosis Coronaria/etiología , Stents Liberadores de Fármacos , Fallo Renal Crónico/complicaciones , Infarto del Miocardio/terapia , Sirolimus/administración & dosificación , Anciano , Causas de Muerte , Comorbilidad , Angiografía Coronaria , Reestenosis Coronaria/mortalidad , Supervivencia sin Enfermedad , Análisis de Falla de Equipo , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Modelos de Riesgos Proporcionales , Diálisis Renal , Factores de Riesgo
13.
J Pharm Biomed Anal ; 50(2): 245-51, 2009 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-19442471

RESUMEN

An ultra-fast, sensitive and versatile radio-liquid chromatographic (LC) procedure was developed and validated for quality control (QC) tests of PET radiopharmaceuticals. For a wide variety of radio-probes, the usual LC conditions were used: (1) column: Waters XBridge RP(18) (50 mm x 3.0 mm ID, 2.5 microm), (2) mobile phase: a mixture of three modifiers (90% CH3CN, ammonium phosphate at pH 2.1 and pH 9.3), and (3) detection: UV absorption and NaI(Tl) scintillation. The introduction of a short column packed with small particles of 2.5 microm allowed excellent separation of target analytes within a very short run time of 1 min; only a 3% decline of radioactivity was observed during QC analysis of (11)C-labelled pharmaceuticals. Combining ammonium-phosphate buffer as the mobile-phase component and low-wavelength UV detection led to an improvement in the applicability and sensitivity. All 34 pharmaceuticals investigated could be successfully applied to determine the specific radioactivity, radiochemical and chemical purity with 10-times better sensitivity than traditional LC. We could analyze different pharmaceuticals in a short period since this system utilized a common column and mobile phase. The proposed procedure fulfils the requirements for routine QC tests in terms of rapidity, sensitivity, simplicity and applicability.


Asunto(s)
Tomografía de Emisión de Positrones , Control de Calidad , Radiofármacos/normas , Radiofármacos/análisis , Reproducibilidad de los Resultados
14.
J Chromatogr A ; 1216(18): 3933-40, 2009 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-19307000

RESUMEN

A rapid and efficient preparative high-performance liquid chromatographic procedure was established to purify short-lived positron emission tomography radio-probes. This method is based on hydrophilic interaction chromatography utilizing a semi-preparative silica column (10 mm I.D.) and a high volatile organic mobile phase (>90% acetonitrile). In nine different radiopharmaceuticals studied, six compounds could be separated from the unlabeled precursor with good resolution and faster elution than its precursor. These characteristics enabled significant shortening of the separation and evaporation processes in the manufacture of short-lived radiopharmaceuticals. Several (11)C-radiopharmaceuticals could be prepared within one half-life of carbon-11 (20.4 min), including radiosynthesis, purification and formulation steps with sufficient radiochemical/chemical purity and high levels of radioactivity/specific radioactivity.


Asunto(s)
Radioisótopos de Carbono/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Electrones , Tomografía de Emisión de Positrones/instrumentación , Radiofármacos/aislamiento & purificación , Radioisótopos de Carbono/química , Semivida , Radiofármacos/química
15.
Ann Nucl Med ; 19(7): 573-9, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16363622

RESUMEN

OBJECTIVE: Bone is one of the most common sites of metastasis in breast cancer patients. Although bone scintigraphy is widely used to detect metastatic breast cancer, the usefulness of 18FDG-PET for detecting bone metastasis has not been clearly evaluated. The purpose of this study was to compare the diagnostic accuracy of 18FDG-PET with bone scintigraphy in detecting bone metastasis in breast cancer patients. METHODS: Forty-four women aged 35 to 81 years (mean, 56 years) with breast cancer were examined in this study. Both 18FDG-PET and bone scintigraphy were performed for each patient with 0-69 day intervals (mean, 11.5 days). The results of each image interpretation were compared retrospectively. Whole-body bones were classified into 9 anatomical regions. Metastases were confirmed at 45/187 regions in 14 patients by bone biopsy or clinical follow-up including other imaging techniques for a period of at least 6 months afterwards. RESULTS: On a region basis, the sensitivity, specificity, and accuracy of 18FDG-PET were 84%, 99% and 95%, respectively. Although these results were comparable to those of bone scintigraphy, the combination of 18FDG-PET and bone scintigraphy improved the sensitivity (98%) and accuracy (97%) of detection. False negative lesions of bone scintigraphy were mostly bone marrow metastases and those of 18FDG-PET were mostly osteoblastic metastases. 18FDG-PET was superior to bone scintigraphy in the detection of osteolytic lesions (92% vs. 73%), but inferior in the detection of osteoblastic lesions (74% vs. 95%). CONCLUSIONS: This study shows that 18FDG-PET tends to be superior to bone scintigraphy in the detection of osteolytic lesions, but inferior in the detection of osteoblastic lesions. 18FDG-PET should play a complementary role in detecting bone metastasis with bone scintigraphy.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Neoplasias de la Mama/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/métodos , Medronato de Tecnecio Tc 99m/análogos & derivados , Imagen de Cuerpo Entero/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
16.
Ann Nucl Med ; 19(4): 267-75, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16097635

RESUMEN

OBJECTIVE: To clarify the relationship between D2 receptor binding and the cerebral metabolic rate for glucose (CMRGlu) in patients with parkinsonism, we simultaneously measured both of these factors, and then compared the results. METHODS: The subjects consisted of 24 patients: 9 with Parkinson's disease (PD), 3 with Juvenile Parkinson's disease (JPD), 9 with multiple system atrophy (MSA), and 3 with progressive supranuclear palsy (PSP). The striatal D2 receptor binding was measured by the C-11 raclopride transient equilibrium method. CMRGlu was investigated by the F-18 fluorodeoxyglucose autoradiographic method. RESULTS: The D2 receptor binding in both the caudate nucleus and putamen showed a positive correlation with the CMRGlu in the PD-JPD group, but the two parameters demonstrated no correlation in the MSA-PSP group. The left/right (L/R) ratio of D2 receptor binding in the putamen showed a positive correlation with that of CMRGlu in the MSA-PSP group, while the two demonsrated no correlation in the PD-JPD group. CONCLUSION: Our PET study showed striatal D2 receptor binding and the CMRGlu to be closely related in patients with parkinsonism, even though the results obtained using the L/R ratios tended to differ substantially from those obtained using absolute values. The reason for this difference is not clear, but this finding may reflect the pathophysiology of these disease entities.


Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Glucosa/metabolismo , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/metabolismo , Tomografía de Emisión de Positrones/métodos , Receptores de Dopamina D2/metabolismo , Adulto , Anciano , Antiparkinsonianos/uso terapéutico , Encéfalo/efectos de los fármacos , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Racloprida/farmacocinética , Radiofármacos/farmacocinética , Distribución Tisular/efectos de los fármacos
17.
Ann Nucl Med ; 19(1): 35-40, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15770971

RESUMEN

OBJECTIVE: The aim of this study is to clarify the period of extraosseous accumulation of (99m)Tc-hydroxymethylenediphosphonate (HMDP) to radiation nephropathy mimicking recurrent or remnant neuroblastoma in the pararenal region. METHODS: We reviewed five neuroblastoma and one ganglioneuroblastoma patients (2 boys and 4 girls aged 1-9 years) who underwent (99m)Tc-HMDP bone scintigraphies periodically before and after radiation therapy. RESULTS: Increased renal uptake coincident with the radiation port appeared in 5 of 6 patients from 0 to 3 months (mean 1.7 months), and persisted up to 7 months after the completion of radiotherapy. Renal uptake of (99m)Tc-HMDP was gradually decreased, and eventually became accumulation defects in 5 of 6 patients from 6 to 17 months (mean 8.9 months) after radiotherapy. CONCLUSION: When extraosseous accumulation is found after radiation therapy in neuroblastoma patients, radiation nephropathy would be a candidate in the differential diagnosis besides recurrent or remnant tumor.


Asunto(s)
Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/metabolismo , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/metabolismo , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/metabolismo , Medronato de Tecnecio Tc 99m/análogos & derivados , Medronato de Tecnecio Tc 99m/farmacocinética , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Niño , Preescolar , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Femenino , Humanos , Lactante , Riñón/diagnóstico por imagen , Riñón/lesiones , Riñón/metabolismo , Riñón/efectos de la radiación , Masculino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/metabolismo , Neuroblastoma/secundario , Traumatismos por Radiación/etiología , Cintigrafía , Radiofármacos/farmacocinética , Radioterapia/efectos adversos
18.
Nucl Med Commun ; 25(11): 1095-102, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15577587

RESUMEN

BACKGROUND: We evaluated the quantitative accuracy of the post-injection transmission-based segmented attenuation correction (SAC) technique and transmissionless calculated attenuation correction (CAC) technique in both 2D and 3D scanning for the brain, and compared the results with those obtained using the pre-injection transmission-based measured attenuation correction (MAC) technique, which is generally accepted as the 'gold standard'. METHODS: We examined [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) on both a cylindrical phantom and in 10 patients with epilepsy. The statistical analyses were performed using both the region of interest (ROI) method and statistical parametric mapping (SPM). RESULTS: In the ROI analysis, [18F] activity concentration values obtained by the SAC technique were well correlated with those obtained by the MAC technique (2D, R2=0.94; 3D, R2=0.98; P<0.001), although these values were underestimated over the entire brain. The CAC technique was also found to have significant correlation with the MAC technique (2D, R2=0.84; 3D, R2=0.86; P<0.001), but this technique showed apparent overestimation or underestimation in several parts of the brain. In the SPM analysis, there were no significant differences between the SAC and MAC technique, while those values obtained by the CAC technique were significantly lower in the parieto-occipital region and higher in the lower frontal region (P<0.001, uncorrected). CONCLUSION: The SAC technique was superior to the CAC technique in both 2D and 3D scanning, although we found that both the SAC and CAC techniques had some problems in quantitative evaluation. We considered that the SAC technique may yield adequate qualitative measurements of the [18F] activity concentration value after global normalization.


Asunto(s)
Algoritmos , Encéfalo/diagnóstico por imagen , Epilepsia/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Técnica de Sustracción , Adulto , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Fantasmas de Imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos/administración & dosificación , Reproducibilidad de los Resultados , Dispersión de Radiación , Sensibilidad y Especificidad
19.
Ann Nucl Med ; 18(2): 131-6, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15195760

RESUMEN

OBJECTIVE: The aim of this study was to investigate the lesion detectability of a gamma camera based coincidence detector system (c-PET system) in comparison to the dedicated PET system (d-PET system), and thereby clarify the feasibility of the clinical application of this system and also describe any factors influencing the lesion detectability of the c-PET system. METHODS: We examined 74 patients including 19 with malignant lymphoma, 16 with lung cancer, 9 with primary malignant bone tumor, 7 with esophageal cancer, 6 with malignant melanoma, 3 with hepatocellular carcinoma, 3 with primary unknown cancer, 2 with breast cancer, 2 with colon cancer, and 7 with others. d-PET images were obtained using ECAT EXACT HR+ at 60 min, followed by c-PET imaging using ECAM at 120 min after the injection of 185 MBq of FDG. Each image was reconstructed without any attenuation correction. In the image interpretation, the whole body was classified into 16 regions (5 superficial regions and 11 deep regions). The FDG accumulation of the lesions was evaluated by visual grading based on the consensus of three nuclear medicine physicians, and the findings were classified into three grades; (++), (+), and (-). The lesions were also classified into 3 groups according to their size: large group (> or =2 cm), middle group (1 < or = <2 cm) and small group (<1 cm). RESULTS: In 627 regions, the abnormal FDG uptake was detected in 109 regions by the d-PET system. Out of 109 regions, the c-PET system could detect the lesions in 91 regions and was false positive in 1 region. Therefore, the sensitivity, specificity, and accuracy of the c-PET system were 83.5%, 99.8% and 97.0%, respectively. Lesion detectability of the small group (54.5%) was significantly lower than that of the large group (97.9%) (p < 0.001) and that of the middle group (93.1%) (p < 0.001); however, the difference in lesion detectability between the large and middle groups was not significant. Neither the degree of FDG accumulation nor the location of the lesion markedly influenced the lesion detectability of the c-PET system. However, when we focused on the large and middle size lesions, the detectability of deep lesions tended to be lower than that of superficial lesions. CONCLUSION: In conclusion, the lesion detectability of the c-PET system was inferior to that of the d-PET system, especially in the case of small lesions. Further examination is required to assess the clinical usefulness of the c-PET system.


Asunto(s)
Análisis de Falla de Equipo/métodos , Fluorodesoxiglucosa F18 , Cámaras gamma , Tomografía de Emisión de Positrones/instrumentación , Tomografía de Emisión de Positrones/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos
20.
Acad Radiol ; 11(5): 489-97, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15147613

RESUMEN

RATIONALE AND OBJECTIVES: To evaluate the reliability of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) values obtained by deconvolution algorithm perfusion-weighted MR imaging (D-PWI), we compared these values with those obtained by first-moment algorithm perfusion-weighted MR imaging (F-PWI) and 15O-PET. SUBJECTS AND METHODS: Six healthy volunteers and eleven patients with chronic occlusive cerebrovascular disease were studied with both perfusion-weighted MR imaging and 15O-PET, and region-of-interest analyses were performed. Normalization factors for CBF and CBV values obtained by D-PWI were determined as the mean values of 15O-PET divided by those of D-PWI in healthy volunteers. Then these values were used in analyzing the data of the patients. RESULTS: The MTT value obtained by D-PWI was 6.1 +/- 0.5 seconds on the non-occluded side, 6.4 +/- 0.7 seconds on the minimally to moderately stenosed side, and 6.7 +/- 1.2 seconds on the severely stenosed to occluded side. These values were significantly correlated with those obtained by F-PWI (r = 0.83; P < .001), and with those obtained by 15O-PET (r = 0.78; P < .05). However, the CBF and CBV values obtained by D-PWI did not correlate with those obtained by 15O-PET. CONCLUSION: MTT values obtained by D-PWI were reliable parameters of cerebral hemodynamics, but the CBF and CBV values obtained by D-PWI were not always reliable.


Asunto(s)
Arteriopatías Oclusivas/fisiopatología , Trastornos Cerebrovasculares/fisiopatología , Angiografía por Resonancia Magnética , Adulto , Anciano , Arteriopatías Oclusivas/diagnóstico por imagen , Volumen Sanguíneo , Circulación Cerebrovascular , Trastornos Cerebrovasculares/diagnóstico por imagen , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioisótopos de Oxígeno , Reproducibilidad de los Resultados , Tomografía Computarizada de Emisión
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