63 research outputs found
Renal Cortical Glucose Uptake Is Decreased in Insulin Resistance and Correlates Inversely With Serum Free-fatty Acids
No full textContext: Studies on human renal metabolism are scanty. Nowadays, functional imaging allows the characterization of renal metabolism in a noninvasive manner. We have recently demonstrated that fluorodeoxyglucose F18 (18F FDG) positron emission tomography can be used to analyze renal glucose uptake (GU) rates, and that the renal cortex is an insulin-sensitive tissue. Objective: To confirm that renal GU is decreased in people with obesity and to test whether circulating metabolites are related to renal GU. Design, Setting and Participants: Eighteen people with obesity and 18 nonobese controls were studied with [18F]FDG positron emission tomography during insulin clamp. Renal scans were obtained ∼60 minutes after [18F]FDG injection. Renal GU was measured using fractional uptake rate and after correcting for residual intratubular [18F]FDG. Circulating metabolites were measured using high-throughput proton nuclear magnetic resonance metabolomics. Results: Cortical GU was higher in healthy nonobese controls compared with people with obesity (4.7 [3.4-5.6] vs 3.1 [2.2-4.3], P = .004, respectively), and it associated positively with the degree of insulin sensitivity (M value) (r = 0.42, P = .01). Moreover, cortical GU was inversely associated with circulating β-OH-butyrate (r = -0.58, P = .009), acetoacetate (r = -0.48, P = .008), citrate (r = −0.44, P = .01), and free fatty acids (r = −0.68, P < .0001), even when accounting for the M value. On the contrary, medullary GU was not associated with any clinical parameters. Conclusion: These data confirm differences in renal cortical GU between people with obesity and healthy nonobese controls. Moreover, the negative correlations between renal cortex GU and free fatty acids, ketone bodies, and citrate are suggestive of substrate competition in the renal cortex
64Cu- and 68Ga-labelled [Nle(14),Lys(40)(Ahx-NODAGA)NH2]-exendin-4 for pancreatic beta cell imaging in rats.
No full textPURPOSE
Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle(14),Lys(40)(Ahx-NODAGA-(64)Cu)NH2]-exendin-4 ([(64)Cu]NODAGA-exendin-4) and [Nle(14),Lys(40)(Ahx-NODAGA-(68)Ga)NH2]-exendin-4 ([(68)Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents.
PROCEDURES
The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated.
RESULTS
We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [(64)Cu]NODAGA-exendin-4 and [(68)Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively.
CONCLUSION
[(64)Cu]NODAGA-exendin-4 might be more effective for labelling islets than [(68)Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [(68)Ga]NODAGA-exendin-4 compared to [(64)Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [(64)Cu]NODAGA-exendin-4 as a clinical tracer
Radiosynthesis of the norepinephrine transporter tracer [F-18]NS12137 via copper-mediated F-18-labelling
No full text[F-18]NS12137 (exo-3-[(6-[F-18]fluoro-2-pyridyl)oxy]8-azabicyclo[3.2.1]octane) is a highly selective norepinephrine transporter (NET) tracer. NETs are responsible for the reuptake of norepinephrine and dopamine and are linked to several neurodegenerative and neuropsychiatric disorders. The aim of this study was to develop a copper-mediated F-18-fluorination method for the production of [F-18]NS12137 with straightforward synthesis conditions and high radiochemical yield and molar activity. [F-18]NS12137 was produced in two steps. Radiofluorination of [F-18]NS12137 was performed via a copper-mediated pathway starting with a stannane precursor and using [F-18]F- as the source of the fluorine-18 isotope. Deprotection was performed via acid hydrolysis. The radiofluorination reaction was nearly quantitative as was the deprotection based on HPLC analysis. The radiochemical yield of the synthesis was 15.1 +/- 0.5%. Molar activity of [F-18]NS12137 was up to 300 GBq/mu mol. The synthesis procedure is straightforward and can easily be automated and adapted for clinical production
Interconversion energy barrier of [Cu((S)-p-NH2-Bn-NOTA)]− complex conformers studied by ion pair chromatography
No full textObservation of ferromagnetic ordering in conjugated polymers exhibiting OMAR effect
No full textWe report observation of ferromagnetic (FM) ordering in π-conjugated polymeric semiconductors, namely regio-regular poly (3-hexyl thiophene) (RRP3HT) and 1-(3-methoxycarbonyl)propyl-1-phenyl-[6,6]-methanofullerene (PCBM), in the temperature range of 5–300 K. Diodes made from these polymers exhibit sizable magnetoresistance (known commonly as OMAR). However, upon blending these two materials, the FM ordering is suppressed by a huge paramagnetic (PM) signal. In the diodes with RRP3HT:PCBM blend showing PM response, OMAR decreases substantially. Particle induced X-ray emission spectroscopy indicate presence of dilute magnetic impurities as residues from the synthesis process in the individual polymers. However the impurity signal is unable to explain the temperature dependence of magnetization in these materials and the observed paramagnetism of the RRP3HT:PCBM blend. We propose a hypothesis for the origin of the FM nature of these polymers based on ours and previously reported experimental observations and pointed out that the reported organic magnetoresistance might have a close correlation with the ferromagnetic interaction in these polymers
Erratum to: (64)Cu- and (68)Ga-Labelled [Nle (14),Lys (40)(Ahx-NODAGA)NH 2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats
No full textObesity risk is associated with brain glucose uptake and insulin resistance
No full textObjective: To investigate whether alterations in brain glucose uptake (BGU), insulin action in the brain-liver axis and whole-body insulin sensitivity occur in young adults in pre-obese state.Methods: Healthy males with either high risk (HR; n = 19) or low risk (LR; n = 22) for developing obesity were studied with [18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography during hyperinsulinemic-euglycemic clamp. Obesity risk was assessed according to BMI, physical activity and parental overweight/obesity and type 2 diabetes. Brain, skeletal muscle, brown adipose tissue (BAT), visceral adipose tissue (VAT) and abdominal and femoral s.c. adipose tissue (SAT) glucose uptake (GU) rates were measured. Endogenous glucose production (EGP) was calculated by subtracting the exogenous glucose infusion rate from the rate of disappearance of [18F]FDG. BGU was analyzed using statistical parametric mapping, and peripheral tissue activity was determined using Carimas Software imaging processing platform.Results: BGU was higher in the HR vs LR group and correlated inversely with whole-body insulin sensitivity (M value) in the HR group but not in the LR group. Insulin-suppressed EGP did not differ between the groups but correlated positively with BGU in the whole population, and the correlation was driven by the HR group. Skeletal muscle, BAT, VAT, abdominal and femoral SAT GU were lower in the HR group as compared to the LR group. Muscle GU correlated negatively with BGU in the HR group but not in the LR group.Conclusion: Increased BGU, alterations in insulin action in the brain-liver axis and decreased whole-body insulin sensitivity occur early in pre-obese state.</p
Solid-Supported Porphyrins Useful for the Synthesis of Conjugates with Oligomeric Biomolecules
No full textFlare on [18F]PSMA-1007 PET/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: possible marker of tumor aggressiveness in treatment-naïve metastatic prostate cancer patients
No full textPurpose Short-term androgen deprivation therapy (ADT) is known to increase heterogeneously prostate-specific membrane antigen (PSMA) expression. This phenomenon might indicate the potential of cancer lesions to respond to ADT. In this prospective study, we evaluated the flare on [F-18]PSMA-1007 PET/CT after ADT in metastatic prostate cancer (PCa). Given that aggressive PCa tends to display FDG uptake, we particularly investigated whether the changes in PSMA uptake might correlate with glucose metabolism.Methods Twenty-five men with newly diagnosed treatment-naive metastatic PCa were enrolled in this prospective registered clinical trial. All the patients underwent [F-18]PSMA-1007 PET/CT immediately before and 3-4 weeks after ADT initiation (degarelix). Before ADT, [F-18]FDG PET/CT was also performed. Standardized uptake values (SUV)max of primary and metastatic lesions were calculated in all PET scans. Serum PSA and testosterone blood samples were collected before the two PSMA PET scans. The changes in PSMA uptake after ADT were represented as Delta SUVmax.Results All the patients reached castration levels of testosterone at the time of the second [F-18]PSMA-1007 PET/CT. Overall, 57 prostate, 314 lymph nodes (LN), and 406 bone lesions were analyzed. After ADT, 104 (26%) bone, 33 (11%) LN, and 6 (11%) prostate lesions showed an increase (>= 20%) in PSMA uptake, with a median Delta SUVmax of + 50%, + 60%, and + 45%, respectively. Among the lesions detected at the baseline [F-18]PSMA-1007 PET/CT, 63% bone and 46% LN were FDG-positive. In these metastases, a negative correlation was observed between the PSMA Delta SUVmax and FDG SUVmax (p Conclusions A heterogeneous increase in PSMA uptake after ADT was detected, most evidently in bone metastases. We observed a negative correlation between the PSMA flare and the intensity of glucose uptake as well as the decrease of serum PSA, suggesting that lesions presenting with such flare might potentially be less aggressive.</p
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