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Enzyme inhibition of dopamine metabolism alters 6-[18 F]FDOPA uptake in orthotopic pancreatic adenocarcinoma
Johanna Tuomela, Sarita Forsback, Laura Haavisto, Tero Vahlberg, Tove J Gr nroos, Olof Solin and Merja Haaparanta-Solin
EJNMMI Research , 2013, DOI: 10.1186/2191-219X-3-18
Abstract: Combined use of [18F]FDG and [18F]FDOPA is suitable for imaging pancreatic tumours. Unequal pancreatic uptake after the employed enzyme inhibitors is due to the blockade of metabolism and therefore increased availability of [18F]FDOPA metabolites, in which uptake differs from that of [18F]FDOPA. Pretreatment with COMT + MAO-A inhibitors improved the differentiation of pancreas from the surrounding tissue and healthy pancreas from tumour. Similar advantage was not achieved using carbidopa.
In vivo characterization of a novel norepinephrine transporter PET tracer [18F]NS12137 in adult and immature Sprague-Dawley rats
Anna K. Kirjavainen,Dan Peters,Francisco R. López-Picón,Jatta S. Takkinen,Merja Haaparanta-Solin,Olof Solin,Sarita Forsback
- , 2019, DOI: 10.7150/thno.29740
Abstract:
Long-Term Monoacylglycerol Lipase Inhibitor Treatment Decelerates Pathological Changes in APP/PS1-21 Mice, but Behavioral Improvements Require Early-Stage Treatment Onset—Short Report  [PDF]
Rea Pihlaja, Noora Lindgren, Annamari Torittu, Anniina Snellman, Merja Haaparanta-Solin, Juha O. Rinne
World Journal of Neuroscience (WJNS) , 2018, DOI: 10.4236/wjns.2018.82014
Abstract: The arachidonic acid (AA) pathway produces several essential proinflammatory eicosanoids. However, in many neurodegenerative diseases, e.g. Alzheimer’s disease (AD), this pathway is chronically hyperactivated. In brain, primarily monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to AA, which is further metabolized to generate many proinflammatory eicosanoids. MAGL inhibition, simultaneously reducing the level of eicosanoids and increasing those of neuroprotective endocannabinoids, has proved efficacious in some AD models, reducing neurotoxic β-amyloid (Aβ) levels and improving memory functions. Here, a MAGL inhibitor, JZL184 was chronically administered (16 mg/kg, i.p., 3 x/wk for 5 mo) for 1 - 1.5 mo and 7 - 8 mo old transgenic (TG) and wild-type (WT) APP/PS1-21 mice modelling cerebral amyloidosis. According to immunohistochemistry, JZL184 significantly increased the expression levels of cannabinoid receptor 1 in older WT and younger TG and WT mice, decreased cannabinoid receptor 2 and oligomeric Aβ in older and younger TG mice and decreased microglia-specific marker Iba1 in younger TG mice, compared to TG mice treated with vehicle only. However, in the Morris Water Maze test, spatial memory functions improved significantly only in younger TG and WT mice, compared to vehicle-treated littermates. These tentative results suggest that chronic, rather long-term MAGL inhibition can decelerate pathological changes in TG APP/PS1-21 mice but it improves memory functions only when administered at an early stage of the pathology
[18F]CFT synthesis and binding to monoamine transporters in rats
Sarita Forsback, P？ivi Marjam？ki, Olli Eskola, J？rgen Bergman, Johanna Rokka, Tove Gr？nroos, Merja Haaparanta, Olof Solin
EJNMMI Research , 2012, DOI: 10.1186/2191-219x-2-3
Abstract: [18F]CFT was synthesized by electrophilic fluorination of a stannylated precursor by using post-target-produced [18F]F2 as a fluorinating agent. The ex vivo 18F-activity biodistribution of [18F]CFT in the brain of rats was studied by autoradiography. The binding of [18F]CFT to the monoamine transporters was studied using in vivo blocking experiments with dopamine transporter [DAT], norepinephrine transporter [NET], or serotonin transporter [SERT] inhibitors. In vivo animal positron emission tomography was used as a comparative method to determine tracer kinetics. Human radiation dose was assessed using OLINDA software.The radiochemical yield of [18F]CFT from the initial [18F]F-, decay corrected to the end of bombardment, was 3.2 ± 1.0%. The specific activity [SA] was 14.5 ± 3.4 GBq/μmol, decay corrected to the end of synthesis. Radiochemical purity exceeded 99%. DAT-specific binding was found in the striatum, locus coeruleus, and pancreas. NET-specific binding was found in the locus coeruleus. SERT-specific binding was not found in any of the studied organs. Effective dose equivalent [EDE] estimated for the standard human model was 12.8 μSv/MBq. Effective dose [ED] was 9.17 μSv/MBq.Post-target-produced high-SA [18F]F2 was used to incorporate18F directly into the phenyl ring of [18F]CFT. The final product had high radiochemical and chemical purities and a high SA for DAT and NET studies in vivo. In periphery, [18F]CFT showed a specific uptake in the pancreas. EDE and ED corresponded well with other18F-radioligands.Dopamine transporters [DAT] are proteins located in the dopaminergic nerve terminals; they regulate the synaptic concentration of dopamine in the brain. Changes in the density and function of DAT in the brain are involved in many neurodegenerative and neuropsychiatric disorders, such as Parkinson's disease and schizophrenia. These changes can be imaged using positron emission tomography [PET].Many radioligands, including [11C]CFT [1] and several [18F]F-labe
Extraordinary Phenomena in Semiconductor-Metal Hybrid Nanostructures Based on Bilinear Conformal Mapping
S. A. Solin
Physics , 2006,
Abstract: We have shown that bilinear conformal mapping can be used to transform 4-lead internally shunted EMR semiconductor-metal hybrid structures to galvanomagnetically equivalent externally shunted 4 lead structures. The latter are compatible with the fabrication of nanoscale EMR devices while the former are not. Mapped rectangular EMR van der Pauw plate exhibit very large EMR values in both macroscopic and nanoscopic form. We have also shown that the mapping procedure applied in the case of EMR will also be applicable to other generalized EXX structures.
Design and Properties of a scanning EMR probe Microscope
S. A. Solin
Physics , 2006,
Abstract: The design, fabrication, and predicted performance of a new type of magnetic scanning probe microscope based on the newly discovered phenomenon of extraordinary magnetoresistance (EMR) is described. It is shown that the new probe should advance the state of the art of both sensitivity and spatial resolution by an order of magnitude or more.
Monitoring near-Earth-object discoveries for imminent impactors
Mikael Granvik,Otto Solin
- , 2018, DOI: 10.1051/0004-6361/201832747
Abstract: Aims. We present an automated system called NEORANGER that regularly computes asteroid-Earth impact probabilities for objects on the Minor Planet Center’s (MPC) Near-Earth-Object Confirmation Page (NEOCP) and sends out alerts of imminent impactors to registered users. In addition to potential Earth-impacting objects, NEORANGER also monitors for other types of interesting objects such as Earth’s natural temporarily-captured satellites.Methods. The system monitors the NEOCP for objects with new data and solves, for each object, the orbital inverse problem, which results in a sample of orbits that describes the, typically highly-nonlinear, orbital-element probability density function (PDF). The PDF is propagated forward in time for seven days and the impact probability is computed as the weighted fraction of the sample orbits that impact the Earth.Results. The system correctly predicts the then-imminent impacts of 2008 TC3 and 2014 AA based on the first data sets available. Using the same code and configuration we find that the impact probabilities for objects typically on the NEOCP, based on eight weeks of continuous operations, are always less than one in ten million, whereas simulated and real Earth-impacting asteroids always have an impact probability greater than 10% based on the first two tracklets available
Hilbert Space Methods for Reduced-Rank Gaussian Process Regression
Arno Solin,Simo S？rkk？
Statistics , 2014,
Abstract: This paper proposes a novel scheme for reduced-rank Gaussian process regression. The method is based on an approximate series expansion of the covariance function in terms of an eigenfunction expansion of the Laplace operator in a compact subset of $\mathbb{R}^d$. On this approximate eigenbasis the eigenvalues of the covariance function can be expressed as simple functions of the spectral density of the Gaussian process, which allows the GP inference to be solved under a computational cost scaling as $\mathcal{O}(nm^2)$ (initial) and $\mathcal{O}(m^3)$ (hyperparameter learning) with $m$ basis functions and $n$ data points. The approach also allows for rigorous error analysis with Hilbert space theory, and we show that the approximation becomes exact when the size of the compact subset and the number of eigenfunctions go to infinity. The expansion generalizes to Hilbert spaces with an inner product which is defined as an integral over a specified input density. The method is compared to previously proposed methods theoretically and through empirical tests with simulated and real data.
Infinite-dimensional Bayesian filtering for detection of quasi-periodic phenomena in spatio-temporal data
Arno Solin,Simo S？rkk？
Statistics , 2013, DOI: 10.1103/PhysRevE.88.052909
Abstract: This paper introduces a spatio-temporal resonator model and an inference method for detection and estimation of nearly periodic temporal phenomena in spatio-temporal data. The model is derived as a spatial extension of a stochastic harmonic resonator model, which can be formulated in terms of a stochastic differential equation (SDE). The spatial structure is included by introducing linear operators, which affect both the oscillations and damping, and by choosing the appropriate spatial covariance structure of the driving time-white noise process. With the choice of the linear operators as partial differential operators, the resonator model becomes a stochastic partial differential equation (SPDE), which is compatible with infinite-dimensional Kalman filtering. The resulting infinite-dimensional Kalman filtering problem allows for a computationally efficient solution as the computational cost scales linearly with measurements in the temporal dimension. This framework is applied to weather prediction and to physiological noise elimination in fMRI brain data.
Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts
Johanna Tuomela, Tove J Gr？nroos, Maija P Valta, Jouko Sandholm, Aleksi Schrey, Jani Sepp？nen, P？ivi Marjam？ki, Sarita Forsback, Ilpo Kinnunen, Olof Solin, Heikki Minn, Pirkko L H？rk？nen
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-596
Abstract: Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([18F]FDG) and hypoxia ([18F]EF5), and intratumoral polarographic measurements of pO2.Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO2 measurements, [18F]EF5 and [18F]FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls.FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts.Hypoxia is a common feature of prostate tumours [1]. A low oxygen concentration is known to make tumour cells resistant to radiation therapy and chemotherapy [2]. Furthermore, there is evidence that hypoxia may lead to increasingly malignant behaviour of tumour cells [3,4]. Hypoxia leads to disruption of microenvironmental homeostasis in tumours, where metabolic changes, involving diffusion gradients of oxygen and glucose, develop at microregional level [5]. A common feature of invasive cancers is altered glucose metabolism, including both aerobic and anaerobic glycolysis [6]. Conversion of glucose to lactic acid in the presence of oxygen is known as aerobic glycolysis or the "Warburg effect". The molecular mechanisms leading to upregulated glycolysis in tum
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