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1.
J Pediatr Gastroenterol Nutr ; 71(5): 604-611, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33093366

RESUMO

OBJECTIVE: In England, 27,500 children are referred annually to hospital with constipation. An objective measure of whole gut transit time (WGTT) could aid management. The current standard WGTT assessment, the x-ray radiopaque marker (ROM) test, gives poor definition of colonic anatomy and the radiation dose required is undesirable in children. Our objective was to develop an alternative magnetic resonance imaging (MRI) WGTT measure to the x-ray ROM test and to demonstrate its initial feasibility in paediatric constipation. METHODS: With the Nottingham Young Person's Advisory Group we developed a small (8 × 4 mm), inert polypropylene capsule shell filled with MRI-visible fat emulsion. The capsule can be imaged using MRI fat and water in-phase and out-of-phase imaging. Sixteen patients with constipation and 19 healthy participants aged 7 to 18 years old were recruited. Following a common ROM protocol, the participants swallowed 24 mini-capsules each day for 3 days and were imaged on days 4 and 7 using MRI. The number of successful studies (feasibility) and WGTT were assessed. Participants' EuroQoL Visual Analogue Scale were also collected and compared between the day before the taking the first set of mini-capsules to the day after the last MRI study day. RESULTS: The mini-capsules were imaged successfully in the colon of all participants. The WGTT was 78 ±â€Š35 hours (mean ±â€Šstandard deviation) for patients, and 36 ±â€Š16 hours, P < 0.0001 for healthy controls. Carrying out the procedures did not change the EuroQoL Visual Analogue Scale scores before and after the procedures. CONCLUSIONS: Magnetic Resonance Imaging in Paediatric Constipation was a first-in-child feasibility study of a new medical device to measure WGTT in paediatric constipation using MRI. The study showed that the new method is feasible and is well tolerated.


Assuntos
Constipação Intestinal , Trânsito Gastrointestinal , Adolescente , Criança , Colo/diagnóstico por imagem , Constipação Intestinal/diagnóstico por imagem , Inglaterra , Estudos de Viabilidade , Humanos , Imageamento por Ressonância Magnética
3.
Diagnostics (Basel) ; 10(3)2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-32235742

RESUMO

Measurement of gastric emptying is of clinical value for a range of conditions. Gamma scintigraphy (GS) has an established role, but the use of magnetic resonance imaging (MRI) has recently increased. Previous comparison studies between MRI and GS showed good correlation, but were performed on separate study days. In this study, the modalities were alternated rapidly allowing direct comparison with no intra-individual variability confounds. Twelve healthy participants consumed 400 g of Technetium-99m (99mTc)-labelled soup test meal (204 kcal) and were imaged at intervals for 150 min, alternating between MRI and GS. The time to empty half of the stomach contents (T1/2) and retention rate (RR) were calculated and data correlated. The average T1/2 was similar for MRI (44 ± 6 min) and GS (35 ± 4 min) with a moderate but significant difference between the two modalities (p < 0.004). The individual T1/2 values were measured, and MRI and GS showed a good positive correlation (r = 0.95, p < 0.0001), as well as all the RRs at each time point up to 120 min. Gastric emptying was measured for the first time by MRI and GS on the same day. This may help with translating the use of this simple meal, known to elicit reliable, physiological, and pathological gastrointestinal motor, peptide, and appetite responses.

4.
Mol Metab ; 31: 45-54, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31918921

RESUMO

OBJECTIVE: Fibroblast growth factor 21 (FGF21) has been shown to rapidly lower body weight in the Siberian hamster, a preclinical model of adiposity. This induced negative energy balance mediated by FGF21 is associated with both lowered caloric intake and increased energy expenditure. Previous research demonstrated that adipose tissue (AT) is one of the primary sites of FGF21 action and may be responsible for its ability to increase the whole-body metabolic rate. The present study sought to determine the relative importance of white (subcutaneous AT [sWAT] and visceral AT [vWAT]), and brown (interscapular brown AT [iBAT]) in governing FGF21-mediated metabolic improvements using the tissue-specific uptake of glucose and lipids as a proxy for metabolic activity. METHODS: We used positron emission tomography-computed tomography (PET-CT) imaging in combination with both glucose (18F-fluorodeoxyglucose) and lipid (18F-4-thiapalmitate) tracers to assess the effect of FGF21 on the tissue-specific uptake of these metabolites and compared responses to a control group pair-fed to match the food intake of the FGF21-treated group. In vivo imaging was combined with ex vivo tissue-specific functional, biochemical, and molecular analyses of the nutrient uptake and signaling pathways. RESULTS: Consistent with previous findings, FGF21 reduced body weight via reduced caloric intake and increased energy expenditure in the Siberian hamster. PET-CT studies demonstrated that FGF21 increased the uptake of glucose in BAT and WAT independently of reduced food intake and body weight as demonstrated by imaging of the pair-fed group. Furthermore, FGF21 increased glucose uptake in the primary adipocytes, confirming that these in vivo effects may be due to a direct action of FGF21 at the level of the adipocytes. Mechanistically, the effects of FGF21 are associated with activation of the ERK signaling pathway and upregulation of GLUT4 protein content in all fat depots. In response to treatment with FGF21, we observed an increase in the markers of lipolysis and lipogenesis in both the subcutaneous and visceral WAT depots. In contrast, FGF21 was only able to directly increase the uptake of lipid into BAT. CONCLUSIONS: These data identify brown and white fat depots as primary peripheral sites of action of FGF21 in promoting glucose uptake and also indicate that FGF21 selectively stimulates lipid uptake in brown fat, which may fuel thermogenesis.


Assuntos
Tecido Adiposo/metabolismo , Metabolismo Energético , Fatores de Crescimento de Fibroblastos/metabolismo , Tecido Adiposo/diagnóstico por imagem , Animais , Cricetinae , Masculino , Phodopus , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
5.
Pharmaceutics ; 11(6)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181662

RESUMO

Nasal delivery of large peptides such as parathyroid 1-34 (PTH 1-34) can benefit from a permeation enhancer to promote absorption across the nasal mucosa into the bloodstream. Previously, we have published an encouraging bioavailability (78%), relative to subcutaneous injection in a small animal preclinical model, for a liquid nasal spray formulation containing the permeation enhancer polyethylene glycol (15)-hydroxystearate (Solutol® HS15). We report here the plasma pharmacokinetics of PTH 1-34 in healthy human volunteers receiving the liquid nasal spray formulation containing Solutol® HS15. For comparison, data for a commercially manufactured teriparatide formulation delivered via subcutaneous injection pen are also presented. Tc-99m-DTPA gamma scintigraphy monitored the deposition of the nasal spray in the nasal cavity and clearance via the inferior meatus and nasopharynx. The 50% clearance time was 17.8 min (minimum 10.9, maximum 74.3 min). For PTH 1-34, mean plasma Cmax of 5 pg/mL and 253 pg/mL were obtained for the nasal spray and subcutaneous injection respectively; relative bioavailability of the nasal spray was ≤1%. Subsequently, we investigated the pharmacokinetics of the liquid nasal spray formulation as well as a dry powder nasal formulation also containing Solutol® HS15 in a crossover study in an established ovine model. In this preclinical model, the relative bioavailability of liquid and powder nasal formulations was 1.4% and 1.0% respectively. The absolute bioavailability of subcutaneously administered PTH 1-34 (mean 77%, range 55-108%) in sheep was in agreement with published human data for teriparatide (up to 95%). These findings have important implications in the search for alternative routes of administration of peptides for the treatment of osteoporosis, and in terms of improving translation from animal models to humans.

6.
Br J Radiol ; 92(1098): 20190020, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30864832

RESUMO

OBJECTIVE: To examine the imaging capability of a novel small field of view hybrid gamma camera (HGC) using 125I seeds prior to surgical use. METHODS: The imaging performance of the camera system was assessed quantitatively and qualitatively at different source depths, source to collimator distances (SCD), activity levels, acquisition times and source separations, utilising bespoke phantoms. RESULTS: The system sensitivity and spatial resolution of the HGC for 125I were 0.41 cps/MBq (at SCD 48 mm) and 1.53 ± 0.23 mm (at SCD 10 mm) respectively. The camera was able to detect the 125I seed at a SCD of 63 mm (with no scattering material in place) in images recorded within a 1-min acquisition time. The detection of the seeds beneath scattering material (simulating deep-seated tumours) was limited to depths of less than 20 mm beneath the skin surface with a SCD of 63 mm and seed activity of 2.43 MBq. Subjective assessments of the hybrid images acquired showed the capability of the HGC for localising the 125I seeds. CONCLUSION: This preliminary ex vivo study demonstrates that the HGC is capable of detecting 125I seeds and could be a useful tool in radioactive seed localisation with the added benefit of providing hybrid optical γ images for guiding breast conserving surgery. ADVANCES IN KNOWLEDGE: The SFOV HGC could provide high resolution fused optical-gamma images of 125I radioactive seeds indicating the potential use in intraoperative surgical procedure such as RSL.


Assuntos
Câmaras gama/normas , Radioisótopos do Iodo/análise , Desenho de Equipamento , Humanos , Imagens de Fantasmas , Sensibilidade e Especificidade
8.
Nucl Med Commun ; 40(1): 73-78, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30371605

RESUMO

BACKGROUND: Radical chemoradiotherapy is the primary treatment for head and neck cancers in many hospitals. Tumour hypoxia causes radiotherapy resistance and is an indicator of poor prognosis for patients. Identifying hypoxia to select patients for intensified or hypoxia-modified treatment regimens is therefore of high clinical importance. PATIENTS AND METHODS: We evaluated hypoxia in a group of patients with newly diagnosed squamous cell head and neck cancer using the hypoxia-selective radiotracer [F]HX4. Patients underwent a single [F]HX4 PET/computed tomography scan prior to beginning chemoradiotherapy. RESULTS: Three out of eight patients recruited were scanned with [F]HX4. Two out of three had pretreatment [F]FDG PET/computed tomography scans available for review. [F]HX4 tumour uptake varied between patients, with tumour to mediastinal ratios ranging from 1 to 3.5. CONCLUSION: The spectrum of [F]HX4 uptake in this small series of patients exemplifies the difference in oxygenation profiles between histologically similar tumours. Performing an additional PET scan with [F]HX4 prior to chemoradiotherapy treatment was logistically challenging in a routine setting, and therefore validation of its clinical impact should be the focus of future studies [EudraCT number 2013-003563-58].


Assuntos
Nitroimidazóis , Tomografia por Emissão de Pósitrons , Planejamento da Radioterapia Assistida por Computador , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Triazóis , Hipóxia Tumoral , Idoso , Quimiorradioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
10.
Int J Pharm ; 535(1-2): 113-119, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29038066

RESUMO

Osteoporosis treatment with PTH 1-34 injections significantly reduces the incidence of bone fracture. Potential further reductions in fracture rate should be observed through nasal spray delivery to address the poor compliance associated with patient dislike of repeated PTH 1-34 subcutaneous injections. In vitro human osteoblast-like Saos-2 cell intracellular cAMP levels were used to define PTH 1-34 nasal spray formulation bioactivity. The chemically synthesised PTH 1-34 had an EC50 of 0.76nM. Absorption enhancers polyethylene glycol (15)-hydroxystearate (Solutol® HS15), poloxamer 407, chitosan or sodium hyaluronate did not diminish the bioactivity of PTH 1-34 within an in vitro cell culture model (p >0.05). We also demonstrated the effectiveness of the transmucosal absorption enhancer Solutol® HS15 in a nasal spray formulation using a preclinical pharmacokinetic model. In Sprague-Dawley rats without the absorption enhancer the uptake of PTH 1-34 into the blood via intranasal delivery produced a Cmax of 2.1±0.5ng/ml compared to 13.7±1.6ng/ml with Solutol® HS15 enhancer (p=0.016) and a Cmax14.8±8ng/ml in subcutaneous injections. Together these data illustrate that the nasal spray formulation bioactivity in vitro is not affected by the nasal spray absorption enhancers investigated, and the Solutol® HS15 nasal spray formulation had an equivalent pharmacokinetic profile to subcutaneous injection in the rat model. The Solutol® HS15 formulation therefore demonstrated potential as a PTH 1-34 nasal spray formulation for the treatment of osteoporosis.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Osteoblastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Teriparatida/administração & dosagem , Adjuvantes Farmacêuticos/química , Administração Intranasal , Animais , Disponibilidade Biológica , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/farmacocinética , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Humanos , Masculino , Absorção Nasal , Osteoblastos/metabolismo , Polietilenoglicóis/química , Ratos Sprague-Dawley , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Ácidos Esteáricos/química , Teriparatida/química , Teriparatida/farmacocinética
11.
Endocrinology ; 158(10): 3090-3096, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28938451

RESUMO

The increased prevalence of obesity and its cardiometabolic implications demonstrates the imperative to identify novel therapeutic targets able to effect meaningful metabolic changes in this population. Antibody-mediated targeting of fibroblast growth factor receptor 1c isoform (FGFR1c) has been shown to ameliorate hyperglycemia and protect from diet- and genetically-induced obesity in rodents and nonhuman primates. However, it is currently unknown which tissue(s) contribute to this glucose-lowering effect. Thus, to elucidate this effect, we treated euglycemic mice with H7, a monoclonal antibody that selectively targets FGFR1c, and used whole-body positron emission computed tomography with a glucose tracer (18F-fluorodeoxyglucose). Treatment with H7 increased basal glucose uptake in white adipose tissue (WAT), brown adipose tissue (BAT), the brain, and liver but reduced it in the quadriceps muscles. Consequentially, blood glucose was significantly reduced in response to treatment. Under insulin-stimulated conditions, the effects of H7 were maintained in WAT, BAT, liver, and muscle. Treatment with H7 decreased triglyceride (TG) content and increased adipose TG lipase content in white adipose tissue, while increasing activation of acetyl coenzyme A carboxylase, suggesting futile cycling of TGs, albeit favoring net hydrolysis. We demonstrated, in vitro, this is a direct effect of treatment in adipose tissue, as basal cellular respiration and glucose uptake were increased in response to treatment. Taken together, these data suggest that antibody-mediated targeting of FGFR1c exerts its powerful glucose-lowering efficacy primarily due to increased glucose uptake in adipose tissue.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Anticorpos Monoclonais/administração & dosagem , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Acetil-CoA Carboxilase/metabolismo , Animais , Anticorpos Monoclonais/uso terapêutico , Glicemia/análise , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ativação Enzimática/efeitos dos fármacos , Glucose/metabolismo , Insulina/farmacologia , Lipase/análise , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Isoformas de Proteínas , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/imunologia , Triglicerídeos/metabolismo
12.
Nucl Med Commun ; 38(9): 729-736, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28704342

RESUMO

INTRODUCTION: Hybrid imaging has proven to be a major innovation in nuclear medicine, allowing the fusion of functional information with anatomical detail. In the past, the use of hybrid imaging such as PET-CT, PET-MRI and SPECT-CT has been of great clinical benefit; however, these scanners are relatively large and bulky. We have developed and investigated the clinical application of a compact small field of view hybrid gamma camera (HGC) that is suitable for small-organ imaging at the patient bedside. PATIENTS AND METHODS: The HGC - consisting of a CsI(Tl) scintillation crystal coupled to an electron-multiplying charge-coupled device and an optical camera - was used in this study. Eligible patients attending the nuclear medicine clinic at Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK, were invited to take part in this study. Following the standard injection of either a Tc-labelled or I-labelled radiopharmaceutical, images of the patient were acquired using the HGC and presented in a fused optical-gamma display. RESULTS: There were 24 patients enrolled in the study (age range between 30 and 83 years, mean: 58.6 years), images of 18 of whom were successfully acquired. These included patients who were undergoing bone, thyroid, lacrimal drainage, DaTscan and lymphatic imaging. In general, the small field of view system was well suited to small-organ imaging. The uptake could be clearly seen in relation to the patient surface anatomy and showed particular promise for lymphatic, thyroid and lacrimal drainage studies. CONCLUSION: This pilot study has demonstrated the first clinical results of hybrid optical-gamma imaging in patients. The use of this system has raised new possibilities for small-organ imaging, in which the localization of radiopharmaceutical uptake can be presented in an anatomical context using optical imaging. The compact nature of the hybrid system offers the potential for bedside investigations and intraoperative use.


Assuntos
Câmaras gama , Aumento da Imagem/instrumentação , Cintilografia/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Miniaturização , Imagens de Fantasmas , Projetos Piloto , Cintilografia/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
EJNMMI Phys ; 4(1): 19, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28685477

RESUMO

BACKGROUND: A prototype anthropomorphic head and neck phantom has been designed to simulate the adult head and neck anatomy including some internal organs and tissues of interest, such as thyroid gland and sentinel lymph nodes (SLNs). The design of the head and neck phantom includes an inner jig holding the simulated SLNs and thyroid gland. The thyroid gland structure was manufactured using three-dimensional (3D) printing taking into consideration the morphology and shape of a healthy adult thyroid gland. RESULT: The head and neck phantom was employed to simulate a situation where there are four SLNs distributed at two different vertical levels and at two depths within the neck. Contrast to noise ratio (CNR) calculations were performed for the detected SLNs at an 80 mm distance between both pinhole collimators (0.5 and 1.0 mm diameters) and the surface of the head and neck phantom with a 100 s acquisition time. The recorded CNR values for the simulated SLNs are higher when the hybrid gamma camera (HGC) was fitted with the 1.0 mm diameter pinhole collimator. For instance, the recorded CNR values for the superficially simulated SLN (15 mm depth) containing 0.1 MBq of 99mTc using 0.5 and 1.0 mm diameter pinhole collimators are 6.48 and 16.42, respectively (~87% difference). Gamma and hybrid optical images were acquired using the HGC for the simulated thyroid gland. The count profiles through the middle of the simulated thyroid gland images provided by both pinhole collimators were obtained. The HGC could clearly differentiate the individual peaks of both thyroid lobes in the gamma image produced by the 0.5-mm pinhole collimator. In contrast, the recorded count profile for the acquired image using the 1.0-mm-diameter pinhole collimator showed broader peaks for both lobes, reflecting the degradation of the spatial resolution with increasing the diameter of the pinhole collimator. CONCLUSIONS: This anthropomorphic head and neck phantom provides a valuable tool for assessing the imaging ability of gamma cameras used for imaging the head and neck region. The standardisation of test phantoms for SFOV gamma systems will provide an opportunity to collect data across various medical centres. The phantom described is cost effective, reproducible, flexible and anatomically representative.

14.
Sci Rep ; 7(1): 4238, 2017 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-28652585

RESUMO

FGF21 exerts profound metabolic effects in Siberian hamsters exposed to long day (LD) photoperiods that increase appetite and adiposity, however these effects are attenuated in short day (SD) animals that display hypophagia and reduced adiposity. The aim of this study was to investigate whether the beneficial effects of a novel mimetic of FGF21 in the LD state are a consequence of increased adiposity or of the central photoperiodic state. This was achieved by investigating effects of FGF21 in aged hamsters, which is associated with reduced adiposity. In LD hamsters with increased adiposity, FGF21 lowered body weight as a result of both reduced daily food intake and increased caloric expenditure, driven by an increase in whole-body fat oxidation. However, in LD animals with reduced adiposity, the effect of FGF21 on body weight, caloric intake and fat oxidation were significantly attenuated or absent when compared to those with increased adiposity. These attenuated/absent effects were underpinned by the inability of FGF21 to increase the expression of key thermogenic genes in interscapular and visceral WAT. Our study demonstrates the efficacy of a novel FGF21 mimetic in hamsters, but reveals attenuated effects in the animal model where adiposity is reduced naturally independent of photoperiod.


Assuntos
Adiposidade/genética , Fatores de Crescimento de Fibroblastos/genética , Obesidade/genética , Phodopus/genética , Tecido Adiposo/fisiologia , Adiposidade/fisiologia , Animais , Peso Corporal , Ritmo Circadiano/genética , Cricetinae , Metabolismo Energético/genética , Humanos , Obesidade/fisiopatologia , Phodopus/fisiologia , Fotoperíodo , Estações do Ano
15.
Sensors (Basel) ; 17(3)2017 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-28282957

RESUMO

The development of low profile gamma-ray detectors has encouraged the production of small field of view (SFOV) hand-held imaging devices for use at the patient bedside and in operating theatres. Early development of these SFOV cameras was focussed on a single modality-gamma ray imaging. Recently, a hybrid system-gamma plus optical imaging-has been developed. This combination of optical and gamma cameras enables high spatial resolution multi-modal imaging, giving a superimposed scintigraphic and optical image. Hybrid imaging offers new possibilities for assisting clinicians and surgeons in localising the site of uptake in procedures such as sentinel node detection. The hybrid camera concept can be extended to a multimodal detector design which can offer stereoscopic images, depth estimation of gamma-emitting sources, and simultaneous gamma and fluorescence imaging. Recent improvements to the hybrid camera have been used to produce dual-modality images in both laboratory simulations and in the clinic. Hybrid imaging of a patient who underwent thyroid scintigraphy is reported. In addition, we present data which shows that the hybrid camera concept can be extended to estimate the position and depth of radionuclide distribution within an object and also report the first combined gamma and Near-Infrared (NIR) fluorescence images.


Assuntos
Câmaras gama , Raios gama , Imagem Óptica , Cintilografia
16.
J Med Chem ; 59(20): 9422-9430, 2016 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-27690460

RESUMO

There is currently no ideal radiotracer for imaging of protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Others are radiolabeled with the short-half-life positron emitter carbon-11, which is rather impractical for many PET centers. Based on the puromycin (6) structural manifold, a series of 10 novel derivatives of 6 was prepared via Williamson ether synthesis from a common intermediate. A bioluminescence assay was employed to study their inhibitory action on protein synthesis, which identified the fluoroethyl analogue 7b as a lead compound. The fluorine-18 analogue was prepared via nucleophilic substitution of the corresponding tosylate precursor in a modest radiochemical yield of 2 ± 0.6% with excellent radiochemical purity (>99%) and showed complete stability over 3 h at ambient temperature.


Assuntos
Proteínas de Bactérias/análise , Proteínas de Bactérias/biossíntese , Tomografia por Emissão de Pósitrons/métodos , Biossíntese de Proteínas , Puromicina/análogos & derivados , Puromicina/análise , Relação Dose-Resposta a Droga , Marcação por Isótopo , Medições Luminescentes , Estrutura Molecular , Puromicina/síntese química , Puromicina/química , Radioisótopos/química , Staphylococcus aureus/metabolismo , Relação Estrutura-Atividade
17.
Br J Radiol ; 89(1066): 20160435, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27537079

RESUMO

OBJECTIVE: The hybrid gamma camera (HGC) has been developed to enhance the localization of radiopharmaceutical uptake in targeted tissues during surgical procedures such as sentinel lymph node (SLN) biopsy. To assess the capability of the HGC, a lymph node contrast (LNC) phantom was constructed to simulate medical scenarios of varying radioactivity concentrations and SLN size. METHODS: The phantom was constructed using two clear acrylic glass plates. The SLNs were simulated by circular wells of diameters ranging from 10 to 2.5 mm (16 wells in total) in 1 plate. The second plate contains four larger rectangular wells to simulate tissue background activity surrounding the SLNs. The activity used to simulate each SLN ranged between 4 and 0.025 MBq. The activity concentration ratio between the background and the activity injected in the SLNs was 1 : 10. The LNC phantom was placed at different depths of scattering material ranging between 5 and 40 mm. The collimator-to-source distance was 120 mm. Image acquisition times ranged from 60 to 240 s. RESULTS: Contrast-to-noise ratio analysis and full-width-at-half-maximum (FWHM) measurements of the simulated SLNs were carried out for the images obtained. Over the range of activities used, the HGC detected between 87.5 and 100% of the SLNs through 20 mm of scattering material and 75-93.75% of the SLNs through 40 mm of scattering material. The FWHM of the detected SLNs ranged between 11.93 and 14.70 mm. CONCLUSION: The HGC is capable of detecting low accumulation of activity in small SLNs, indicating its usefulness as an intraoperative imaging system during surgical SLN procedures. ADVANCES IN KNOWLEDGE: This study investigates the capability of a novel small-field-of-view (SFOV) HGC to detect low activity uptake in small SLNs. The phantom and procedure described are inexpensive and could be easily replicated and applied to any SFOV camera, to provide a comparison between systems with clinically relevant results.


Assuntos
Câmaras gama , Linfonodo Sentinela/diagnóstico por imagem , Desenho de Equipamento , Humanos , Imagens de Fantasmas , Compostos Radiofarmacêuticos/farmacocinética , Biópsia de Linfonodo Sentinela
18.
Eur J Nucl Med Mol Imaging ; 43(7): 1360-75, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26780912

RESUMO

(18)F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. (18)F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of (18)F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited "quantification" to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of "true" quantification. A discussion is then presented on how semiquantitative information is currently used in clinical (18)F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and "personalized" quantification techniques.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estadiamento de Neoplasias , Resultado do Tratamento
19.
Curr Biol ; 25(22): 2997-3003, 2015 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-26549257

RESUMO

Hypothalamic tanycytes are considered to function as sensors of peripheral metabolism. To facilitate this role, they express a wide range of receptors, including fibroblast growth factor receptor 1 (FGFR1). Using a monoclonal antibody (IMC-H7) that selectively antagonizes the FGFR1c isoform, we investigated possible actions of FGFR1c in a natural animal model of adiposity, the Siberian hamster. Infusion of IMC-H7 into the third ventricle suppressed appetite and increased energy expenditure. Likewise, peripheral treatment with IMC-H7 decreased appetite and body weight and increased energy expenditure and fat oxidation. A greater reduction in body weight and caloric intake was observed in response to IMC-H7 during the long-day fat state as compared to the short-day lean state. This enhanced response to IMC-H7 was also observed in calorically restricted hamsters maintained in long days, suggesting that it is the central photoperiodic state rather than the peripheral adiposity that determines the response to FGFR1c antagonism. Hypothalamic thyroid hormone availability is controlled by deiodinase enzymes (DIO2 and DIO3) expressed in tanycytes and is the key regulator of seasonal cycles of energy balance. Therefore, we determined the effect of IMC-H7 on hypothalamic expression of these deiodinase enzymes. The reductions in food intake and body weight were always associated with decreased expression of DIO2 in the hypothalamic ependymal cell layer containing tanycytes. These data provide further support for the notion the tanycytes are an important component of the mechanism by which the hypothalamus integrates central and peripheral signals to regulate energy intake and expenditure.


Assuntos
Anticorpos Monoclonais/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Adiposidade/fisiologia , Animais , Anticorpos Monoclonais/imunologia , Ritmo Circadiano/fisiologia , Cricetinae , Hipotálamo/metabolismo , Masculino , Modelos Animais , Phodopus , Fotoperíodo , Isoformas de Proteínas/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/imunologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Magreza/metabolismo , Hormônios Tireóideos/metabolismo , Redução de Peso/efeitos dos fármacos
20.
Nucl Med Commun ; 36(11): 1134-42, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26352214

RESUMO

OBJECTIVE: To develop a method for the assessment of small field of view (SFOV) gamma cameras using a novel phantom designed to simulate the localization of sentinel nodes in the presence of a high-activity injection site. MATERIALS AND METHODS: The phantom consisted of a cube-shaped acrylic glass support frame. Sixteen acrylic glass plates and nine bars were stacked within the frame to allow a variable configuration of the simulated node depth and node-to-injection site separation. Syringes filled with Tc were used to simulate activity at the injection site and node. Scintigraphic imaging was carried out and the images were assessed subjectively and quantitatively through calculation of the contrast-to-noise ratio. The detection performance of an SFOV gamma camera was then compared with that of a large field of view gamma camera. RESULTS: The detectability studies showed that the SFOV gamma camera could detect low activity in nodes by visual examination of images and with contrast-to-noise ratios ranging from 3 to 62. In particular, the phantom showed the limits of node detection using an SFOV gamma camera over activity ratios less than 1 : 100 and at depths below 45 mm with 25 mm of node-to-injection site separation. Visual subjective assessment of images acquired under the same conditions showed that the SFOV gamma camera was superior to a large field of view camera for the detection of nodes at a node-to-injection site separation of 25 mm. CONCLUSION: A low-cost phantom has been designed and fabricated that provides a versatile method for the assessment of SFOV gamma cameras intended for sentinel node imaging.


Assuntos
Câmaras gama , Biópsia de Linfonodo Sentinela/instrumentação , Desenho de Equipamento , Imagens de Fantasmas , Razão Sinal-Ruído
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