Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 344
Filter
1.
Neuroimage Clin ; 42: 103616, 2024.
Article in English | MEDLINE | ID: mdl-38763039

ABSTRACT

PURPOSE: The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. MATERIALS AND METHODS: Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. RESULTS: Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808-0.861), SUVmean (r = 0.794-0.851) and TBR (r = 0.643-0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. CONCLUSION: [18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.


Subject(s)
Brain Neoplasms , Choline , Glioma , Humans , Glioma/diagnostic imaging , Glioma/metabolism , Middle Aged , Male , Female , Choline/analogs & derivatives , Choline/metabolism , Choline/pharmacokinetics , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/metabolism , Adult , Aged , Positron-Emission Tomography/methods , Kinetics , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals/pharmacokinetics , Prospective Studies , Neoplasm Grading
2.
Biosci Biotechnol Biochem ; 88(6): 648-655, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38490741

ABSTRACT

Lysophosphatidylcholine (LPC) is present in various foods and contains a choline moiety such as in glycerophosphocholine (GPC). However, the potential of LPC as a choline source remains unclear. This study investigated the single-dose pharmacokinetics of 480 mg soy-derived LPC in 12 healthy men compared with that of either soy oil with the same lipid amount (placebo) or GPC with the same choline amount. Both LPC and GPC supplementation increased plasma choline, serum phospholipid, and serum triglyceride concentrations, but neither of them significantly elevated plasma trimethylamine N-oxide concentration. In addition, although the intake of LPC slightly increased plasma LPC16:0, LPC18:2, and total LPC concentrations, their concentrations remained within physiological ranges. No adverse events were attributed to the LPC supplementation. To the best of our knowledge, this study is the first to compare LPC and GPC pharmacokinetics in humans and shows that LPC can be a source of choline.


Subject(s)
Choline , Glycerylphosphorylcholine , Glycine max , Lysophosphatidylcholines , Humans , Male , Lysophosphatidylcholines/blood , Glycerylphosphorylcholine/pharmacokinetics , Glycerylphosphorylcholine/blood , Choline/pharmacokinetics , Choline/blood , Adult , Glycine max/chemistry , Dietary Supplements , Young Adult , Triglycerides/blood , Methylamines/blood , Methylamines/pharmacokinetics
3.
AJR Am J Roentgenol ; 217(5): 1206-1216, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34009000

ABSTRACT

BACKGROUND. COVID-19 vaccination may trigger reactive lymphadenopathy, confounding imaging interpretation. There has been limited systematic analysis of PET findings after COVID-19 vaccination. OBJECTIVE. The purpose of this study was to evaluate the frequency and characteristics of abnormal FDG and 11C-choline uptake on PET performed after COVID-19 vaccination. METHODS. This retrospective study included 67 patients (43 men and 24 women; mean [± SD] age, 75.6 ± 9.2 years) who underwent PET examination between December 14, 2020, and March 10, 2021, after COVID-19 vaccination and who had undergone prevaccination PET examination without visible axillary node uptake. A total of 52 patients received the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech; hereafter referred to as the Pfizer-BioNTech vaccine), and 15 received the SARS-CoV-2 mRNA-1273 vaccine (Moderna; hereafter referred to as the Moderna vaccine). Sixty-six of the patients underwent PET/CT, and one underwent PET/MRI. Fifty-four PET examinations used FDG, and 13 used 11C-choline. PET was performed a median of 13 and 10 days after vaccination for patients who had received one (n = 44) and two (n = 23) vaccine doses, respectively. Two nuclear medicine physicians independently reviewed images and were blinded to injection laterality and the number of days since vaccination. Lymph node or deltoid SUVmax greater than the blood pool SUVmax was considered positive. Interreader agreement was assessed, and the measurements made by the more experienced physician were used for subsequent analysis. RESULTS. Positive axillary lymph node uptake was observed in 10.4% (7/67) of patients (7.4% [4/54] of FDG examinations and 23.1% [3/13] of 11C-choline examinations); of the patients with positive axillary lymph nodes, four had received the Pfizer vaccine, and three had received the Moderna vaccine. Injection laterality was documented for five of seven patients with positive axillary lymph nodes and was ipsilateral to the positive node in all five patients. PET was performed within 24 days of vaccination for all patients with a positive node. One patient showed extraaxillary lymph node uptake (ipsilateral supraclavicular uptake on FDG PET). Ipsilateral deltoid uptake was present in 14.5% (8/55) of patients with documented injection laterality, including 42.9% (3/7) of patients with positive axillary lymph nodes. Interreader agreement for SUV measurements (expressed as intraclass correlation coefficients) ranged from 0.600 to 0.988. CONCLUSION. Increased axillary lymph node or ipsilateral deltoid uptake is occasionally observed on FDG or 11C-choline PET performed after COVID-19 vaccination with the Pfizer-BioNTech or Moderna vaccine. CLINICAL IMPACT. Interpreting physicians should recognize characteristics of abnormal uptake on PET after COVID-19 vaccination to guide optimal follow-up management and reduce unnecessary biopsies.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Deltoid Muscle/diagnostic imaging , Lymphadenopathy/diagnostic imaging , Lymphadenopathy/etiology , Magnetic Resonance Imaging , Positron Emission Tomography Computed Tomography , 2019-nCoV Vaccine mRNA-1273 , Aged , Axilla/diagnostic imaging , BNT162 Vaccine , Carbon Radioisotopes/pharmacokinetics , Choline/pharmacokinetics , Female , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Male , Radiopharmaceuticals/pharmacokinetics , Retrospective Studies , SARS-CoV-2
4.
Health Phys ; 120(1): 80-85, 2021 01.
Article in English | MEDLINE | ID: mdl-32826522

ABSTRACT

Gallium-68 (Ga)-PSMA and F-Choline are two radionuclides that have already shown high potential for the detection of prostate cancer. The comparison between these two radionuclides has several advantages in radiation protection. The aim of this prospective study was to identify which of these two radionuclides can help in predicting the equivalent dose using the maximum standard uptake value (SUVmax) of normal organs, the kidneys. Two groups of 40 patients (total n = 80) who underwent PET/CT using Ga or F for diagnosis of prostate cancer between April 2018 and December 2018 at the American University of Beirut Medical Center were included. First, the dose rates were measured after 1 h of radionuclide uptake at 1 m distance with background of 0.015 µSv h. Then, SUVmax for kidneys were determined from images obtained with PET/CT 1 h after injection of both radionuclides. The ratios of the equivalent doses to the SUVmax for kidneys were compared for both Ga-PSMA and F-Choline. There is a positive moderate relationship between the SUVmax for kidneys and the Ga dose rate after 1 h of injection at 1 m distance from the abdomen (p-value = 0.023 < 0.05). This relationship is statistically significant. However, there is a very low negative relationship between the SUVmax kidney and F dose rate after 1 h of injection at 1 m distance from the abdomen (p-value = 0.93 > 0.05). This relationship is not statistically significant. This leads to the suggestion that we can predict the equivalent dose due to Ga by indicating the SUVmax from the PET/CT images.


Subject(s)
Choline/analogs & derivatives , Fluorine Radioisotopes/pharmacokinetics , Gallium Isotopes/pharmacokinetics , Gallium Radioisotopes/pharmacokinetics , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Radiopharmaceuticals/pharmacokinetics , Choline/pharmacokinetics , Diagnostic Reference Levels , Humans , Kidney/diagnostic imaging , Kidney/radiation effects , Ligands , Male , Prospective Studies , Radiation Dosage , Radiation Protection , Therapeutic Equivalency
5.
J Med Chem ; 63(24): 15960-15978, 2020 12 24.
Article in English | MEDLINE | ID: mdl-33271015

ABSTRACT

We present a novel series of radioiodinated tracers and potential theranostics for diseases accompanied by pathological function of proteins involved in choline transport. Unlike choline analogues labeled with 11C or 18F that are currently used in the clinic, the iodinated compounds described herein are applicable in positron emission tomography, single-photon emission computed tomography, and potentially in therapy, depending on the iodine isotope selection. Moreover, favorable half-lives of iodine isotopes result in much less challenging synthesis by isotope exchange reaction. Six of the described compounds were nanomolar ligands, and the best compound possessed an affinity 100-fold greater than that of choline. Biodistribution data of 125I-labeled ligands in human prostate carcinoma bearing (PC-3) mice revealed two compounds with a biodistribution profile superior to that of [18F]fluorocholine.


Subject(s)
Choline/analogs & derivatives , Fluorine Radioisotopes/pharmacokinetics , Iodine Radioisotopes/pharmacokinetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Radioactive Tracers , Radiopharmaceuticals/pharmacokinetics , Animals , Apoptosis , Cell Proliferation , Choline/pharmacokinetics , Humans , Male , Mice , Mice, SCID , Positron-Emission Tomography , Prostatic Neoplasms/diagnostic imaging , Tissue Distribution , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
6.
Nutrients ; 12(8)2020 Aug 05.
Article in English | MEDLINE | ID: mdl-32764281

ABSTRACT

Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.


Subject(s)
Cardiovascular Diseases/metabolism , Choline/metabolism , Gastrointestinal Microbiome , Methylamines/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Renal Insufficiency, Chronic/metabolism , Animals , Biological Availability , Choline/genetics , Choline/pharmacokinetics , Diet/methods , Dysbiosis/metabolism , Genotype , Humans , Inflammatory Bowel Diseases/metabolism , Liver/metabolism
8.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 39(2): 84-91, mar.-abr. 2020. ilus, tab
Article in Spanish | IBECS | ID: ibc-196348

ABSTRACT

OBJETIVO: Determinar las razones de los diferentes patrones de captación suprarrenal de la colina radiomarcada en pacientes con cáncer de próstata o renal sometidos a una tomografía por emisión de positrones/tomografía computarizada con 18F-Fluoroetilcolina (18F-Colina). MÉTODOS: Se analizaron 49 estudios de tomografía por emisión de positrones/tomografía computarizada con colina radiomarcada (96 glándulas suprarrenales), determinándose su morfología, el patrón de captación y el valor de captación máximo estandarizado. Se registraron, evaluaron o contabilizaron otros 15 parámetros más, se calcularon los índices de parámetros escogidos y se comprobó su correlación con la captación de las glándulas suprarrenales. RESULTADOS: Las glándulas suprarrenales presentaron un amplio abanico de intensidades de captación de la colina radiomarcada (rango: 2-7,9), así como diferentes patrones de captación (difuso, focal o mixto). La captación máxima en la glándula suprarrenal derecha (4,3+/-1,2) se correlacionó positivamente con el grosor del parénquima en su punto de captación máxima (5,3mm +/-1,5; p = 0,000). La captación máxima en las glándulas derecha e izquierda, así como la captación suprarrenal media se correlacionaron con la captación máxima en la hipófisis (p = 0,000, p = 0,000 y p=0001, respectivamente), así como con la captación máxima en hígado (p = 0,008, p = 0,000 y p = 0,011, respectivamente). En el grupo estudiado no hubo correlación significativa entre los valores de captación estandarizada de las glándulas suprarrenales y el tratamiento hormonal ni con la edad de los pacientes. CONCLUSIONES: La variabilidad de la captación del radiotrazador de la colina en las glándulas suprarrenales depende probablemente del metabolismo corporal global y de la función hipofisaria expresada a través de correlaciones estadísticamente significativas con la captación hepática e hipofisaria. En la tomografía por emisión de positrones de las glándulas suprarrenales normales, debe evaluarse con precaución aquellos patrones de captación predominantemente focales o mixtos con áreas de captación focal, con el fin de evitar errores diagnósticos


PURPOSE: To find reasons of different radioactive choline adrenal uptake in prostate or renal cancer patients who underwent 18F-fluoroethylcholine positron emission tomography/computed tomography. METHODS: Forty-nine positron emission tomography/computed tomography studies with radioactive choline (96 adrenal glands) were analysed with respect to the adrenal glands shape, uptake pattern and maximum standardised uptake value. Fifteen other parameters were recorded, assessed or counted, ratios of chosen parameters were calculated, and checked for correlation with adrenal glands uptake. RESULTS: Adrenal glands presented a wide range of radioactive choline uptake intensities (range 2-7.9) and different uptake patterns (diffuse, focal or mixed). Maximum uptake in the right (4.3+/-1.2) adrenal gland positively correlated with the thickness of the parenchyma at the point of maximal uptake (5.3mm+/-1.5) (p = 0.000). Maximum uptake in the right and left adrenal gland, as well as mean adrenal gland uptake, correlated with maximum uptake in the pituitary gland (p = 0.000, p = 0.000 and p = 0.001, respectively) and with maximum uptake in liver (p = 0.008, p = 0.000 and p = 0.011, respectively). Neither hormonal treatment nor patients' age significantly correlated with standardised uptake values of adrenal glands in the studied group. CONCLUSIONS: The variability of radiocholine uptake in adrenal glands depends probably on overall body metabolism and hypophyseal function expressed by statistically significant correlation with liver and pituitary gland uptake. Predominant focal or mixed with focal areas uptake patterns on positron emission tomography in normal in computed tomography adrenal glands should be assessed with caution to avoid a diagnostic mistake


Subject(s)
Humans , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Adrenal Glands/diagnostic imaging , Choline/analogs & derivatives , Fluorine Radioisotopes/pharmacokinetics , Tomography, X-Ray Computed , Adrenal Glands/anatomy & histology , Adrenal Glands/metabolism , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/metabolism , Choline/pharmacokinetics , Liver/diagnostic imaging , Liver/metabolism , Positron-Emission Tomography , Tomography, X-Ray Computed/methods , Retrospective Studies
9.
Article in English, Spanish | MEDLINE | ID: mdl-32192907

ABSTRACT

AIM: To standardize acquisition protocols for 18F-Choline PET/CT to prevent from urine interference, to determine the best time point for the whole-body study, and to assess whether "dual point" acquisition allows for differentiating malignant vs. benign lesions. METHODS: One hundred consecutive patients with prostate cancer were prospectively studied. Immediately after 18F-Choline injection, a pelvis study was acquired, and a whole-body was subsequently obtained 1 and 2 hours p.i. Mean SUVmax was obtained in regions and for every sequential imaging. Mean analysis (χ2) and SUV percentage change (2/1 hours; 1 hours/0 min) were obtained. Metabolic pattern dynamics were assessed: accumulative vs. clearance. Patient follow-up after therapy and directed classification whenever ethically possible were performed. RESULTS: Fifty-three prostate foci, without disturbing urinary activity was ever found on early images. Accumulative pattern in 42, with percentage increase was: 0 min/1 hour: +16.7% (χ20.94); 1/2 hours: +10,0% (χ2 0.83). Clearance pattern in 11, with percentage decrease: 0 min/1 hour: -21.4% (χ20.91): -7.7% (χ20.85), corresponding in 7 to initial staging and in 4 post-radiotherapy biochemical recurrence. Every infradiaphragmatic uptake (n: 24) showed accumulative pattern, with percentage increase of +9.1% (χ20.97), all of them depicted on early imaging. As for 12 supradiaphragmantic uptake, 8 of them showed clearance pattern with percentage decrease: -13.0% (χ20.95). Accumulative pattern showed in 4 of them with percentage increase +13.0% (χ2 0.96), thus being assessed as invasive/malignant. Every bone uptake (n: 18) showed accumulative pattern, with percentage increase: +17.1% (χ20.95), all of them depicted on 1 hour imaging. CONCLUSIONS: As for prostate assessment is concerned, dual point at 0 min/1 hour proved to be the best procedure. As for supradiaphragmatic lymph-nodes detection, dual point with 1/2 hours performed best. As for infradiaphragmatic and bone involvement, as well as for inconclusive findings, the 2 hour imaging increased our diagnostic confidence.


Subject(s)
Adenocarcinoma/diagnostic imaging , Choline/analogs & derivatives , Fluorine Radioisotopes , Positron Emission Tomography Computed Tomography/standards , Prostatic Neoplasms/diagnostic imaging , Radiopharmaceuticals , Aged , Aged, 80 and over , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/secondary , Choline/pharmacokinetics , Choline/urine , Diagnosis, Differential , Fluorine Radioisotopes/pharmacokinetics , Fluorine Radioisotopes/urine , Humans , Lymphatic Metastasis/diagnostic imaging , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Pelvis/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Prospective Studies , Prostatic Diseases/diagnostic imaging , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/urine , Time Factors , Whole Body Imaging
10.
Article in English, Spanish | MEDLINE | ID: mdl-32014467

ABSTRACT

PURPOSE: To find reasons of different radioactive choline adrenal uptake in prostate or renal cancer patients who underwent 18F-fluoroethylcholine positron emission tomography/computed tomography. METHODS: Forty-nine positron emission tomography/computed tomography studies with radioactive choline (96 adrenal glands) were analysed with respect to the adrenal glands shape, uptake pattern and maximum standardised uptake value. Fifteen other parameters were recorded, assessed or counted, ratios of chosen parameters were calculated, and checked for correlation with adrenal glands uptake. RESULTS: Adrenal glands presented a wide range of radioactive choline uptake intensities (range 2-7.9) and different uptake patterns (diffuse, focal or mixed). Maximum uptake in the right (4.3±1.2) adrenal gland positively correlated with the thickness of the parenchyma at the point of maximal uptake (5.3mm±1.5) (p=0.000). Maximum uptake in the right and left adrenal gland, as well as mean adrenal gland uptake, correlated with maximum uptake in the pituitary gland (p=0.000, p=0.000 and p=0.001, respectively) and with maximum uptake in liver (p=0.008, p=0.000 and p=0.011, respectively). Neither hormonal treatment nor patients' age significantly correlated with standardised uptake values of adrenal glands in the studied group. CONCLUSIONS: The variability of radiocholine uptake in adrenal glands depends probably on overall body metabolism and hypophyseal function expressed by statistically significant correlation with liver and pituitary gland uptake. Predominant focal or mixed with focal areas uptake patterns on positron emission tomography in normal in computed tomography adrenal glands should be assessed with caution to avoid a diagnostic mistake.


Subject(s)
Adrenal Glands/diagnostic imaging , Choline/analogs & derivatives , Fluorine Radioisotopes/pharmacokinetics , Positron Emission Tomography Computed Tomography , Adrenal Glands/anatomy & histology , Adrenal Glands/metabolism , Adult , Aged , Aged, 80 and over , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/metabolism , Choline/pharmacokinetics , Humans , Liver/diagnostic imaging , Liver/metabolism , Male , Middle Aged , Positron Emission Tomography Computed Tomography/methods , Retrospective Studies
11.
Parasitology ; 147(1): 58-64, 2020 01.
Article in English | MEDLINE | ID: mdl-31556865

ABSTRACT

It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage against Plasmodium yoelii BY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes, P < 0.05) and other control groups (P ⩽ 0.05) at the doses of 4.4, 8.8, 17.6 µmol (kg·d)-1, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P < 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.


Subject(s)
Artemisinins/chemistry , Choline/chemistry , Liposomes/pharmacology , Liposomes/pharmacokinetics , Plasmodium yoelii/drug effects , Animals , Antimalarials/pharmacokinetics , Antimalarials/pharmacology , Antimalarials/therapeutic use , Artemisinins/pharmacokinetics , Artemisinins/pharmacology , Artemisinins/therapeutic use , Choline/pharmacokinetics , Choline/pharmacology , Choline/therapeutic use , Liposomes/chemistry , Liposomes/therapeutic use , Malaria/drug therapy , Mice , Mice, Inbred ICR , Rats , Rats, Sprague-Dawley
12.
Clin Physiol Funct Imaging ; 40(2): 106-113, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31794112

ABSTRACT

AIM: To validate a deep-learning (DL) algorithm for automated quantification of prostate cancer on positron emission tomography/computed tomography (PET/CT) and explore the potential of PET/CT measurements as prognostic biomarkers. MATERIAL AND METHODS: Training of the DL-algorithm regarding prostate volume was performed on manually segmented CT images in 100 patients. Validation of the DL-algorithm was carried out in 45 patients with biopsy-proven hormone-naïve prostate cancer. The automated measurements of prostate volume were compared with manual measurements made independently by two observers. PET/CT measurements of tumour burden based on volume and SUV of abnormal voxels were calculated automatically. Voxels in the co-registered 18 F-choline PET images above a standardized uptake value (SUV) of 2·65, and corresponding to the prostate as defined by the automated segmentation in the CT images, were defined as abnormal. Validation of abnormal voxels was performed by manual segmentation of radiotracer uptake. Agreement between algorithm and observers regarding prostate volume was analysed by Sørensen-Dice index (SDI). Associations between automatically based PET/CT biomarkers and age, prostate-specific antigen (PSA), Gleason score as well as overall survival were evaluated by a univariate Cox regression model. RESULTS: The SDI between the automated and the manual volume segmentations was 0·78 and 0·79, respectively. Automated PET/CT measures reflecting total lesion uptake and the relation between volume of abnormal voxels and total prostate volume were significantly associated with overall survival (P = 0·02), whereas age, PSA, and Gleason score were not. CONCLUSION: Automated PET/CT biomarkers showed good agreement to manual measurements and were significantly associated with overall survival.


Subject(s)
Choline/pharmacokinetics , Fluorine Radioisotopes/pharmacokinetics , Image Interpretation, Computer-Assisted/methods , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Deep Learning , Humans , Male , Middle Aged , Prognosis , Prostate/diagnostic imaging , Prostate/metabolism , Reproducibility of Results , Survival Analysis , Young Adult
13.
Nutrients ; 11(10)2019 Oct 22.
Article in English | MEDLINE | ID: mdl-31652561

ABSTRACT

As an essential nutrient, the organic water-soluble compound choline is important for human health. Choline is required for numerous biological processes, including the synthesis of neurotransmitters, and it is an important prerequisite for structural integrity and the functioning of cells. A choline-rich diet provides crucial choline sources, yet additional choline dietary supplements might be needed to fully meet the body's requirements. Dependent on the structure of choline in different sources, absorption and metabolism may differ and strongly impact the bioavailability of circulating choline. This study in healthy volunteers aimed to compare the pharmacokinetics of free choline and of selected choline metabolites between the single dose intake of phosphatidylcholine, present in SuperbaBoostTM krill oil, and choline bitartrate salt. Results demonstrate that albeit free choline levels in plasma were comparable between both choline sources, peak choline concentration was reached significantly later upon intake of SuperbaBoostTM. Moreover, the occurrence of choline metabolites differed between the study products. Levels of the biologically important metabolites betaine and dimethylglycine (DMG) were higher, while levels of trimethylamine N-oxide (TMAO) were substantially lower upon intake of SuperbaBoostTM compared to choline bitartrate.


Subject(s)
Choline/metabolism , Choline/pharmacokinetics , Euphausiacea/chemistry , Phosphatidylcholines/metabolism , Phosphatidylcholines/pharmacokinetics , Adolescent , Adult , Aged , Animals , Biological Products , Choline/administration & dosage , Choline/blood , Cross-Over Studies , Female , Fish Oils/metabolism , Fish Oils/pharmacokinetics , Humans , Kinetics , Male , Middle Aged , Phosphatidylcholines/administration & dosage , Phosphatidylcholines/blood , Young Adult
15.
J Agric Food Chem ; 67(27): 7748-7754, 2019 Jul 10.
Article in English | MEDLINE | ID: mdl-31203621

ABSTRACT

Choline and its metabolites have diverse and important functions in many physiological processes, especially for anabolic metabolism in growth and reproduction. Besides endogenous biosynthesis and direct choline supplement, choline esters in the diet are another source of choline in the body. Phenolic choline esters are a group of unique dietary choline esters rich in the seeds of Brassicaceae plants, among which sinapine is a choline ester of sinapic acid abundant in rapeseed. In this study, 40 nursery pigs were fed with rapeseed-derived feed ingredients (RSF) or soybean meal for 3 weeks (20 pigs/diet). The metabolic fate of sinapine-derived choline in RSF was examined by comparing the distribution of choline and its metabolites in digesta, liver, and serum samples by liquid chromatography-mass spectrometry analysis. The results showed that choline was released from extensive hydrolysis of sinapine in the small intestine. However, sinapine-derived choline did not increase the levels of choline and its major metabolites, including betaine, phosphocholine, and glycerophosphocholine, in the liver and serum. Instead, RSF feeding increased trimethylamine (TMA), the microbial metabolite of choline, in the large intestine and further increased trimethylamine N-oxide (TMAO), the oxidation metabolite of TMA, in the liver and serum. Overall, these results suggested that sinapine-derived choline from rapeseed feeding had limited influences on the post-absorption choline pool as a result of its low bioavailability but may serve as a major source of TMAO through microbial metabolism in nursery pigs. Improving the bioavailability of sinapine-derived choline might have the potential to modify the nutritional values and functionalities of rapeseed meal in swine feeding.


Subject(s)
Brassica rapa/chemistry , Choline/analogs & derivatives , Choline/analysis , Diet/veterinary , Methylamines/blood , Sus scrofa/blood , Animal Feed/analysis , Animals , Biological Availability , Choline/blood , Choline/chemistry , Choline/metabolism , Choline/pharmacokinetics , Gastrointestinal Microbiome/physiology , Hydrolysis , Liver/chemistry , Male
17.
Cell Metab ; 29(6): 1350-1362.e7, 2019 06 04.
Article in English | MEDLINE | ID: mdl-30982734

ABSTRACT

Choline is a vitamin-like nutrient that is taken up via specific transporters and metabolized by choline kinase, which converts it to phosphocholine needed for de novo synthesis of phosphatidylcholine (PC), the main phospholipid of cellular membranes. We found that Toll-like receptor (TLR) activation enhances choline uptake by macrophages and microglia through induction of the choline transporter CTL1. Inhibition of CTL1 expression or choline phosphorylation attenuated NLRP3 inflammasome activation and IL-1ß and IL-18 production in stimulated macrophages. Mechanistically, reduced choline uptake altered mitochondrial lipid profile, attenuated mitochondrial ATP synthesis, and activated the energy sensor AMP-activated protein kinase (AMPK). By potentiating mitochondrial recruitment of DRP1, AMPK stimulates mitophagy, which contributes to termination of NLRP3 inflammasome activation. Correspondingly, choline kinase inhibitors ameliorated acute and chronic models of IL-1ß-dependent inflammation.


Subject(s)
Choline/metabolism , Choline/pharmacokinetics , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Macrophages/metabolism , Animals , Butanes/pharmacology , Cells, Cultured , Cryopyrin-Associated Periodic Syndromes/genetics , Cryopyrin-Associated Periodic Syndromes/metabolism , Cryopyrin-Associated Periodic Syndromes/pathology , Female , HEK293 Cells , Humans , Intestinal Absorption/drug effects , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Organic Cation Transport Proteins/genetics , Organic Cation Transport Proteins/metabolism , Pyridinium Compounds/pharmacology
18.
J Nucl Med ; 60(8): 1111-1117, 2019 08.
Article in English | MEDLINE | ID: mdl-30630941

ABSTRACT

PET is increasingly used for prostate cancer (PCa) diagnostics. Important PCa radiotracers include 68Ga-prostate-specific membrane antigen HBED-CC (68Ga-PSMA), 18F-DCFPyL, 18F-fluoromethylcholine (18F-FCH), and 18F-dihydrotestosterone (18F-FDHT). Knowledge on the variability of tracer uptake in healthy tissues is important for accurate PET interpretation, because malignancy is suspected only if the uptake of a lesion contrasts with its background. Therefore, the aim of this study was to quantify uptake variability of PCa tracers in healthy tissues and identify stable reference regions for PET interpretation. Methods: A total of 232 PCa PET/CT scans from multiple hospitals was analyzed, including 87 68Ga-PSMA scans, 50 18F-DCFPyL scans, 68 18F-FCH scans, and 27 18F-FDHT scans. Tracer uptake was assessed in the blood pool, lung, liver, bone marrow, and muscle using several SUVs (SUVmax, SUVmean, SUVpeak). Variability in uptake between patients was analyzed using the coefficient of variation (COV%). For all tracers, SUV reference ranges (95th percentiles) were calculated, which could be applicable as image-based quality control for future PET acquisitions. Results: For 68Ga-PSMA, the lowest uptake variability was observed in the blood pool (COV, 19.9%), which was significantly more stable than all other tissues (COV, 29.8%-35.2%; P = 0.001-0.024). For 18F-DCFPyL, the lowest variability was observed in the blood pool and liver (COV, 14.4% and 21.7%, respectively; P = 0.001-0.003). The least variable 18F-FCH uptake was observed in the liver, blood pool, and bone marrow (COV, 16.8%-24.2%; P = 0.001-0.012). For 18F-FDHT, low uptake variability was observed in all tissues, except the lung (COV, 14.6%-23.6%; P = 0.001-0.040). The different SUV types had limited effect on variability (COVs within 3 percentage points). Conclusion: In this multicenter analysis, healthy tissues with limited uptake variability were identified, which may serve as reference regions for PCa PET interpretation. These reference regions include the blood pool for 68Ga-PSMA and 18F-DCFPyL and the liver for 18F-FCH and 18F-FDHT. Healthy tissue SUV reference ranges are presented and applicable as image-based quality control.


Subject(s)
Antigens, Surface/analysis , Choline/analogs & derivatives , Dihydrotestosterone/pharmacokinetics , Gallium Radioisotopes/pharmacokinetics , Glutamate Carboxypeptidase II/analysis , Lysine/analogs & derivatives , Urea/analogs & derivatives , Aged , Choline/pharmacokinetics , Fluorine Radioisotopes/pharmacokinetics , Humans , Lysine/pharmacokinetics , Male , Middle Aged , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography , Quality Control , Reference Values , Reproducibility of Results , Tissue Distribution , Urea/pharmacokinetics
19.
Int. braz. j. urol ; 44(5): 900-905, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-975628

ABSTRACT

ABSTRACT Objectives: To test the ability of dynamic 11C-PET / CT to discriminate cancerous tissue from background tissue in patients with localized prostate cancer. Materials and Methods: Twenty-four consecutive patients with prostate cancer were prospectively evaluated with dynamic 11C-choline PET / CT prior to radical prostatectomy. The PET / CT scan was divided into 18 sequences of 5 seconds each, followed by 9 sequences of 60 seconds each. Whole-mount sections of harvested prostates served as reference standards. Volumes of interest were positioned on the dynamic PET / CT images and the following quantitative variables were calculated: perfusion coefficient (K1), washout constant (K2), area under the curve (AUC) at 175 and 630 seconds, and average and maximum standardized uptake values (SUVavg, and SUVmax). Wilcoxon signed-ranks test was used to compare benign and cancerous areas of the prostate. Results: Areas of cancerous tissue were characterized by higher SUVavg and SUVmax than areas of benign tissue (3.67 ± 2.7 vs. 2.08 ± 1.3 and 5.91 ± 4.4 vs. 3.71 ± 3.7, respectively, P < 0.001), in addition to a higher K1 (0.95 ± 0.58 vs. 0.43 ± 0.24, P < 0.001) and greater cumulative tracer uptake, represented by the AUC at 175 and 630 seconds (P <0.001). No associations were found between dynamic parameters and preoperative prostate specific antigen level or Gleason score. Conclusions: In this pilot study, 11C-choline PET / CT demonstrated increased tracer uptake with higher values of static and dynamic parameters in areas of prostate cancer compared to areas of benign tissue. Larger studies are warranted to validate these results and examine the potential applicability of 11C-choline dynamic PET / CT for the diagnosis of prostate cancer.


Subject(s)
Humans , Male , Prostatic Neoplasms/diagnostic imaging , Carbon Radioisotopes/pharmacokinetics , Choline/pharmacokinetics , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/pathology , Pilot Projects , Prospective Studies , Sensitivity and Specificity , Neoplasm Grading , Middle Aged
20.
Int Braz J Urol ; 44(5): 900-905, 2018.
Article in English | MEDLINE | ID: mdl-30088719

ABSTRACT

OBJECTIVES: To test the ability of dynamic 11C-PET / CT to discriminate cancerous tissue from background tissue in patients with localized prostate cancer. MATERIALS AND METHODS: Twenty-four consecutive patients with prostate cancer were prospectively evaluated with dynamic 11C-choline PET / CT prior to radical prostatectomy. The PET / CT scan was divided into 18 sequences of 5 seconds each, followed by 9 sequences of 60 seconds each. Whole-mount sections of harvested prostates served as reference standards. Volumes of interest were positioned on the dynamic PET / CT images and the following quantitative variables were calculated: perfusion coefficient (K1), washout constant (K2), area under the curve (AUC) at 175 and 630 seconds, and average and maximum standardized uptake values (SUVavg, and SUVmax). Wilcoxon signed-ranks test was used to compare benign and cancerous areas of the prostate. RESULTS: Areas of cancerous tissue were characterized by higher SUVavg and SUVmax than areas of benign tissue (3.67 ± 2.7 vs. 2.08 ± 1.3 and 5.91 ± 4.4 vs. 3.71 ± 3.7, respectively, P < 0.001), in addition to a higher K1 (0.95 ± 0.58 vs. 0.43 ± 0.24, P < 0.001) and greater cumulative tracer uptake, represented by the AUC at 175 and 630 seconds (P <0.001). No associations were found between dynamic parameters and preoperative prostate specific antigen level or Gleason score. CONCLUSIONS: In this pilot study, 11C-choline PET / CT demonstrated increased tracer uptake with higher values of static and dynamic parameters in areas of prostate cancer compared to areas of benign tissue. Larger studies are warranted to validate these results and examine the potential applicability of 11C-choline dynamic PET / CT for the diagnosis of prostate cancer.


Subject(s)
Carbon Radioisotopes/pharmacokinetics , Choline/pharmacokinetics , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Humans , Male , Middle Aged , Neoplasm Grading , Pilot Projects , Prospective Studies , Prostatic Neoplasms/pathology , Sensitivity and Specificity
SELECTION OF CITATIONS
SEARCH DETAIL
...