scholarly journals Effects of Anesthesia and Species on the Uptake or Binding of Radioligands In Vivo in the Göttingen Minipig

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Aage K. O. Alstrup ◽  
Anne M. Landau ◽  
James E. Holden ◽  
Steen Jakobsen ◽  
Anna C. Schacht ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tracer Uptake ◽  
Adrenoceptor Antagonist ◽  
Positron Emission ◽  
Neuroscience Research ◽  
Initial Clearance ◽  
Alpha2 Adrenoceptor ◽  
Kinetics Of ◽  
Volumes Of Distribution

Progress in neuroscience research often involves animals, as no adequate alternatives exist to animal models of living systems. However, both the physiological characteristics of the species used and the effects of anesthesia raise questions of common concern. Here, we demonstrate the confounding influences of these effects on tracer binding in positron emission tomography (PET). We determined the effects of two routinely used anesthetics (isoflurane and propofol) on the binding of two tracers of monoamine function, [C11]SCH23390, a tracer of the dopamine D1 and D5 receptors, and the alpha2-adrenoceptor antagonist, [C11]yohimbine, in Göttingen minipigs. The kinetics of SCH23390 in the pigs differed from those of our earlier studies in primates. With two different graphical analyses of uptake of SCH23390, the initial clearance values of this tracer were higher with isoflurane than with propofol anesthesia, indicative of differences in blood flow, whereas no significant differences were observed for the volumes of distribution of yohimbine. The study underscores the importance of differences of anesthesia and species when the properties of radioligands are evaluated under different circumstances that may affect blood flow and tracer uptake. These differences must be considered in the choice of a particular animal species and mode of anesthesia for a particular application.

scholarly journals The Influence of Tissue Heterogeneity on Results of Fitting Nonlinear Model Equations to Regional Tracer Uptake Curves: With an Application to Compartmental Models Used in Positron Emission Tomography

1987 ◽  
Vol 7 (2) ◽  
pp. 214-229 ◽  
Author(s):  
K. Herholz ◽  
C. S. Patlak
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Glucose Metabolism ◽  
Capillary Permeability ◽  
Input Function ◽  
Tracer Uptake ◽  
Compartmental Models ◽  
Emission Tomography ◽  
Tissue Heterogeneity ◽  
Positron Emission

An analytical method based on Taylor expansions was developed to analyze errors caused by tissue heterogeneity in dynamic positron emission tomography (PET) measurements. Some general rules concerning the effect of parameter variances and covariances were derived. The method was further applied to various compartmental models currently used for measurement of blood flow, capillary permeability, glucose metabolism, and tracer binding. Blood flow and capillary permeability are shown to be generally underestimated in heterogenous tissue, the underestimation being more severe for slowly decaying, constant or increasing input functions rather than for bolus input, and increasing with measurement time. Typical errors caused by the heterogeneity due to insufficient separation between gray and white matter by a PET scanner with full width at half-maximum (FWHM)= 5 to 10 mm resolution range between–0.9 and–6% in dynamic CBF measurements with intravenous (i. v.) bolus injection of 15O-water or inhalation of 18F-fluoromethane and total measurement times of6 or 10 min, respectively. Binding or metabolic rates determined with tracers that are essentially trapped in tissue (e.g., FDG for measurement of cerebral glucose metabolism) are only slightly overestimated (0.5–3.0%) at typical measurement times and are essentially independent of the shape of the input function. The error increases considerably if tracer accumulation is very slow, however, or if short measurement times [<5/(k2 + k3)] are used. Some rate constants are also subject to larger errors.

scholarly journals A Simplified in vivo Autoradiographic Strategy for the Determination of Regional Cerebral Blood Flow by Positron Emission Tomography: Theoretical Considerations and Validation Studies in the Rat

1982 ◽  
Vol 2 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Myron D. Ginsberg ◽  
Alan H. Lockwood ◽  
Raul Busto ◽  
Ronald D. Finn ◽  
Cathy M. Butler ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
Animal Studies ◽  
Blood Flow Rate ◽  
Emission Tomography ◽  
Regional Cerebral Blood ◽  
Positron Emission

A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= z). Integrated cranial activity C̄ B is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that [Formula: see text] where each of the terms A x is a readily evaluated function of the blood flow rate constant k, the brain:blood partition coefficient for the tracer, the cranial activity integration limits T1 and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of C̄ B vs. k, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CBF in vivo = CBFclassical X 0.99 − 0.02 (units in ml g−1 min−1; correlation coefficient r = 0.966).

scholarly journals Noninvasive and Quantitative Monitoring of the Distributions and Kinetics of MicroRNA-Targeting Molecules in Vivo by Positron Emission Tomography

2019 ◽  
Vol 16 (4) ◽  
pp. 1507-1515 ◽  
Author(s):  
Jussi Mäkilä ◽  
Anu Kiviniemi ◽  
Tiina Saanijoki ◽  
Heidi Liljenbäck ◽  
Meeri Käkelä ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Positron Emission ◽  
Quantitative Monitoring ◽  
Kinetics Of

Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb

2013 ◽  
Vol 305 (2) ◽  
pp. H163-H172 ◽  
Author(s):  
Ilkka Heinonen ◽  
Maria Wendelin-Saarenhovi ◽  
Kimmo Kaskinoro ◽  
Juhani Knuuti ◽  
Mika Scheinin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Extraction ◽  
Adrenoceptor Antagonist ◽  
Leg Muscles ◽  
Exercise Condition ◽  
Positron Emission ◽  
Adrenoceptor Agonist ◽  
Neuronal Regulation ◽  
Human Limb

The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ∼40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min−1·100 g−1 in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min−1·100 g−1) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min−1·100 g−1). During exercise, NE reduced exercising muscle BF by ∼16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT ( P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.

Quantification of Cerebral A1 Adenosine Receptors in Humans using [18F]CPFPX and PET

2004 ◽  
Vol 24 (3) ◽  
pp. 323-333 ◽  
Author(s):  
Philipp T Meyer ◽  
Dirk Bier ◽  
Marcus H Holschbach ◽  
Christian Boy ◽  
Ray A Olsson ◽  
...  
Keyword(s):  
Compartment Model ◽  
Graphical Analysis ◽  
Attractive Alternative ◽  
The Novel ◽  
Tissue Compartment ◽  
Arterial Blood ◽  
Positron Emission ◽  
Pet Scanning ◽  
Kinetics Of

Adenosine is an important neuromodulator. Basic cerebral effects of adenosine are exerted by the A1 adenosine receptor (A1AR), which is accessible in vivo by the novel ligand [18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([18F]CPFPX) and positron emission tomography (PET). The present study investigates the applicability of kinetic models to describe the cerebral kinetics of [18F]CPFPX in order to quantify A1AR density in vivo. Six healthy volunteers underwent dynamic PET scanning and arterial blood sampling after bolus injection of [18F]CPFPX. For quantitative analysis, a standard two-tissue compartment model (2TCM) was compared with a one-tissue compartment model (1TCM) and Logan's graphical analysis (GA). The 2TCM described the cerebral kinetics of [18F]CPFPX significantly better than the 1TCM (in all regions and subjects examined). The estimated values of the regional total distribution volumes ( DVt) correlated strongly between the 2TCM and GA (linear regression r2 = 0.99, slope: 1.007). The DVt correlation between the 2TCM and the 1TCM was comparably high, but there was a significant bias towards lower DVt estimates given by the 1TCM (r2: 0.99, slope: 0.929). It is concluded that a 2TCM satisfactorily accounts for the cerebral kinetics of [18F]CPFPX. GA represents an attractive alternative method of analysis.

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