scholarly journals Reference Region Approaches in PET: a Comparative Study on Multiple Radioligands

2013 ◽  
Vol 33 (6) ◽  
pp. 888-897 ◽  
Author(s):  
Francesca Zanderigo ◽  
R Todd Ogden ◽  
Ramin V Parsey
Keyword(s):  
Rate Constant ◽  
Transfer Rate ◽  
Arterial Input Function ◽  
Likelihood Estimation ◽  
Input Function ◽  
Graphical Analysis ◽  
Binding Potential ◽  
Reference Region ◽  
Data Set ◽  
Transfer Rate Constant

Reference region (RR) approaches (RRAs) for positron emission tomography (PET) brain studies aim to obtain full quantification without arterial input function (IF) sampling, an invasive and costly procedure. Although they need a reliable RR and are only able to estimate the nondisplaceable binding potential (BPND), RRAs are widely used. If quantitatively reliable, then RRAs can greatly benefit PET investigations, but their suitability can vary widely from radioligand to radioligand. This study compares estimates of BPND both using IF data and several common RRAs on an extensive data set for each of several radioligands. In addition, two new methods, likelihood estimation in graphical analysis with RR and a bootstrapping algorithm for estimating precision, are presented here for the first time. Although many factors contribute to the performance of each RRA, our results suggest that the kinetics in the RR have a role. In particular, RRAs tend to be good when (1) the RR distribution volume is high; (2) the transfer rate constant from plasma to free compartment in the RR is high; and (3) the transfer rate constant from free to plasma compartment in the RR is low.

scholarly journals Regional Heterogeneity of 5-HT1A Receptors in Human Cerebellum as Assessed by Positron Emission Tomography

2005 ◽  
Vol 25 (7) ◽  
pp. 785-793 ◽  
Author(s):  
Ramin V Parsey ◽  
Victoria Arango ◽  
Doreen M Olvet ◽  
Maria A Oquendo ◽  
Ronald L Van Heertum ◽  
...  
Keyword(s):  
White Matter ◽  
Arterial Input Function ◽  
Input Function ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Reference Region ◽  
Nonspecific Binding ◽  
Cerebellar White Matter ◽  
Way 100635

Two measures used in brain imaging are binding potential (BP) and the specific to nonspecific equilibrium partition coefficient ( V3“). V3” determined using the 5-HT1A ligand [11C]WAY-100635 is sensitive to changes in the free and nonspecific binding of the ligand in the reference region ( V2). Healthy female volunteers have higher 5-HT1A BP but not V3“ compared with men, because V2 is higher in women. While there could be several explanations for this observation, we hypothesized that women have more 5-HT1A receptors in the cerebellum. We explore the cerebellum to define a subregion that more accurately represents the free and nonspecific binding, potentially allowing the use of V3”. A quantitative autoradiogram in human brain using [3H]WAY-100635 identified a cerebellar subregion devoid of 5-HT1A receptors. In vivo 5-HT1A receptors were evaluated using [11C]WAY-100635 in 12 healthy women and 13 healthy men. Each subject had a metabolite-corrected arterial input function. The autoradiogram demonstrates the lowest concentration of 5-HT1A receptors in the cerebellar white matter (CW) and highest concentration in the cerebellar vermis (CV). The CW volume of distribution ( VT) is lower than CV. Cerebellar white matter is adequately modeled by a one-tissue compartmental model, while a two-tissue model is necessary to model CV or the total cerebellum (CT). Women have a higher CW VT compared with men, suggesting a difference in V2. Use of CW improves identifiability and time stability of BP in cortical regions. Cerebellar white matter might be a better reference region for use in future 5-HT1A studies using [11C]WAY-100635. With CW as a reference region, V3“ cannot be used to detect differences in 5-HT1A receptors between men and women, suggesting the need for arterial input functions to determine BP.

scholarly journals Synthesis and preclinical evaluation of [11C]MTP38 as a novel PET ligand for phosphodiesterase 7 in the brain

2020 ◽  
Author(s):  
Naoyuki Obokata ◽  
Chie Seki ◽  
Takeshi Hirata ◽  
Jun Maeda ◽  
Hideki Ishii ◽  
...  
Keyword(s):  
Arterial Input Function ◽  
Inflammatory Diseases ◽  
Input Function ◽  
Binding Potential ◽  
Dependent Manner ◽  
Reference Tissue ◽  
Molar Activity ◽  
The Brain

AbstractPurposePhosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in-vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7.Methods[11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in-vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND.Results[11C]MTP38 was synthesized with radiochemical purity ≥ 99.4% and molar activity of 38.6 ± 12.6 GBq/μmol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In-vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated VT values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hill’s sigmoidal function.ConclusionWe have provided the first successful preclinical demonstration of in-vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.

Connecting charge transfer kinetics to device parameters of a narrow-bandgap polymer-based solar cell

2016 ◽  
Vol 18 (38) ◽  
pp. 26550-26561 ◽  
Author(s):  
Jongwoo Song ◽  
Younah Lee ◽  
Boa Jin ◽  
Jongdeok An ◽  
Hyunmin Park ◽  
...  
Keyword(s):  
Charge Transfer ◽  
Solar Cell ◽  
Kinetic Model ◽  
Rate Constant ◽  
Transfer Rate ◽  
Polymer Solar Cell ◽  
Transfer Rate Constant ◽  
Charge Transfer Rate ◽  
Narrow Bandgap

The spectroscopic charge transfer rate constant was compared with the PV properties of a polymer solar cell using a kinetic model.

scholarly journals Influence of the Potential on the Charge-Transfer Rate Constant of Photooxidation of Water over α-Fe2O3 and Ti-Doped α-Fe2O3

2013 ◽  
Vol 29 (09) ◽  
pp. 1954-1960
Author(s):  
SHANGGUAN Peng-Peng ◽  
◽  
TONG Shao-Ping ◽  
LI Hai-Li ◽  
LENG Wen-Hua ◽  
...  
Keyword(s):  
Charge Transfer ◽  
Rate Constant ◽  
Transfer Rate ◽  
Transfer Rate Constant ◽  
Charge Transfer Rate

scholarly journals Evaluation of Methods for Generating Parametric (R)-[11C]PK11195 Binding Images

2007 ◽  
Vol 27 (9) ◽  
pp. 1603-1615 ◽  
Author(s):  
Alie Schuitemaker ◽  
Bart NM van Berckel ◽  
Marc A Kropholler ◽  
Reina W Kloet ◽  
Cees Jonker ◽  
...  
Keyword(s):  
Basis Function ◽  
Arterial Input Function ◽  
Parametric Method ◽  
Compartmental Analysis ◽  
Accurate Method ◽  
Graphical Analysis ◽  
Binding Potential ◽  
Reference Tissue ◽  
Parametric Images ◽  
Arterial Blood

Activated microglia can be visualised using ( R)-[11C]PK11195 (1-[2-chlorophenyl]- N-methyl- N-[1-methyl-propyl]-3-isoquinoline carboxamide) and positron emission tomography (PET). In previous studies, various methods have been used to quantify ( R)-[11C]PK11195 binding. The purpose of this study was to determine which parametric method would be best suited for quantifying ( R)-[11C]PK11195 binding at the voxel level. Dynamic ( R)-[11C]PK11195 scans with arterial blood sampling were performed in 20 healthy and 9 Alzheimer's disease subjects. Parametric images of both volume of distribution ( Vd) and binding potential ( BP) were obtained using Logan graphical analysis with plasma input. In addition, BP images were generated using two versions of the basis function implementation of the simplified reference tissue model, two versions of Ichise linearisations, and Logan graphical analysis with reference tissue input. Results of the parametric methods were compared with results of full compartmental analysis using nonlinear regression. Simulations were performed to assess accuracy and precision of each method. It was concluded that Logan graphical analysis with arterial input function is an accurate method for generating parametric images of Vd. Basis function methods, one of the Ichise linearisations and Logan graphical analysis with reference tissue input provided reasonably accurate and precise estimates of BP. In pathological conditions with reduced flow rates or large variations in blood volume, the basis function method is preferred because it produces less bias and is more precise.

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