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1.  Assessment of receptor occupancy-over-time of two dopamine transporter inhibitors by [11C]CIT and target controlled infusion 
Eriksson, Olof | Långström, Bengt | Josephsson, Ray
Upsala Journal of Medical Sciences  2011;116(2):100-106.
Introduction
Occupancy-over-time was determined for two dopamine transporter (DAT) inhibitors through modeling of their ability to displace the PET ligand [11C]CIT. The tracer was held at a pseudo steady state in a reference tissue by target controlled infusion.
Methods
Rhesus monkeys (n = 5) were given [11C]CIT and studied with a PET scanner. Tracer uptake in the reference tissue cerebellum was held at a pseudo steady state by use of target controlled infusion. The pharmacokinetics/pharmacodynamics(PK/PD) of [11C]CIT was assessed through the simplified reference tissue model (SRTM). Bupropion (n = 2) and GBR-12909 (n = 2) receptor occupancies were estimated through modeling of their effects on [11C]CIT displacement.
Results
There was a high uptake of [11C]CIT in striatum, which contains a high DAT density. The reference tissue cerebellum had a comparatively low uptake. The modeling of [11C]CIT PK/PD properties in striatum showed high binding potential (BP = 5.34 ± 0.78). Both DAT inhibitors caused immediate displacement of [11C]CIT after administration. The occupancy-over-time was modeled as a mono-exponential function, describing initial maximal occupancy (Occ0) and rate of ligand–receptor dissociation (koff). GBR-12909 showed irreversible binding (koff = 0) after an initial occupancy of 76.1%. Bupropion had a higher initial occupancy (84.5%) followed by a release half-life of 33 minutes (koff = 0.021).
Conclusions
The proposed model can be used for assessment of in-vivo occupancy-over-time of DAT ligands by use of target controlled infusion of [11C]CIT. The concept of assessing drug–receptor interactions by studying perturbations of a PET tracer from a pseudo steady state can be transferred to other CNS systems.
doi:10.3109/03009734.2011.563878
PMCID: PMC3078538  PMID: 21443419
CCIP; [11C]CIT; DAT inhibitor; SRTM; TCI
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2.  External quantification of myocardial perfusion by exponential infusion of positron-emitting radionuclides. 
Hack, S N | Eichling, J O | Bergmann, S R | Welch, M J | Sobel, B E
Journal of Clinical Investigation  1980;66(5):918-927.
A technique was developed and evaluated using the exponential infusion of positron-emitting diffusible tracers to quantitate myocardial perfusion. The approach employs a parameter that rapidly reaches a constant value as a function of tracer delivery rate, isotope decay constant, and the monotonically increasing tissue radioactivity. Isolated rabbit hearts with controlled flow were used to evaluate the approach, because tracer kinetics in such preparations mimic those in vivo. Accordingly, exponential infusions of H2 15O and [11C]butanol were administered to 25 isolated rabbit hearts perfused with Krebs-Henseleit solution (KH) alone or KH enriched with erythrocytes (KH-RBC, hematocrit = 40). With flow varied from 1.2 to 5 ml/g per min in eight KH hearts infused with H2 15O, actual and estimated flow correlated closely (r = 0.95, n = 52 determinations). For the KH-RBC hearts, flow was varied from 0.3 to 1.5 ml/g per min. Actual and estimated flow correlated significantly for both the 14 KH-RBC hearts infused with H2 15O (r = 0.90, n = 89 determinations) and the 3 KH-RBC hearts infused with [11C]butanol (r = 0.93, n = 13 determinations). In addition, the required exponentially increasing arterial tracer concentrations were shown to be attainable in vivo in dogs and rhesus monkeys after intravenous exponential administrations of tracer. The results suggest that the approach developed employing exponential tracer infusion permits accurate measurement of myocardial perfusion and that it should prove useful in the noninvasive measurement of regional myocardial perfusion in vivo by positron emission tomography.
PMCID: PMC371526  PMID: 6968756
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3.  An Internet-Based “Kinetic Imaging System” (KIS) for MicroPET 
Huang, Sung-Cheng | Truong, David | Wu, Hsiao-Ming | Chatziioannou, Arion F. | Shao, Weber | Wu, Anna M. | Phelps, Michael E.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging  2005;7(5):330-341.
Many considerations, involving understanding and selection of multiple experimental parameters, are required to perform MicroPET studies properly. The large number of these parameters/variables and their complicated interdependence make their optimal choice nontrivial. We have a developed kinetic imaging system (KIS), an integrated software system, to assist the planning, design, and data analysis of MicroPET studies. The system serves multiple functions–education, virtual experimentation, experimental design, and image analysis of simulated/experimental data–and consists of four main functional modules–“Dictionary,” “Virtual Experimentation,” “Image Analysis,” and “Model Fitting.” The “Dictionary” module provides didactic information on tracer kinetics, pharmacokinetic, MicroPET imaging, and relevant biological/pharmacological information. The “Virtual Experimentation” module allows users to examine via computer simulations the effect of biochemical/pharmacokinetic parameters on tissue tracer kinetics. It generates dynamic MicroPET images based on the user's assignment of kinetics or kinetic parameters to different tissue organs in a 3-D digital mouse phantom. Experimental parameters can be adjusted to investigate the design options of a MicroPET experiment. The “Image Analysis” module is a full-fledged image display/manipulation program. The “Model Fitting” module provides model-fitting capability for measured/simulated tissue kinetics. The system can be run either through the Web or as a stand-alone process. With KIS, radiotracer characteristics, administration method, dose level, imaging sequence, and image resolution-to-noise tradeoff can be evaluated using virtual experimentation. KIS is designed for biology/pharmaceutical scientists to make learning and applying tracer kinetics fun and easy.
doi:10.1007/s11307-005-0014-3
PMCID: PMC3009470  PMID: 16132473
Tracer kinetics; MicroPET; Virtual experimentation; Molecular imaging
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4.  Propagation of Blood Function Errors to the Estimates of Kinetic Parameters with Dynamic PET 
Cheng, Yafang | Yetik, İmam Şamil
International Journal of Biomedical Imaging  2010;2011:234679.
Dynamic PET, in contrast to static PET, can identify temporal variations in the radiotracer concentration. Mathematical modeling of the tissue of interest in dynamic PET can be simplified using compartment models as a linear system where the time activity curve of a specific tissue is the convolution of the tracer concentration in the plasma and the impulse response of the tissue containing kinetic parameters. Since the arterial sampling of blood to acquire the value of tracer concentration is invasive, blind methods to estimate both blood input function and kinetic parameters have recently drawn attention. Several methods have been developed, but the effect of accuracy of the estimated blood function on the estimation of the kinetic parameters is not studied. In this paper, we present a method to compute the error in the kinetic parameter estimates caused by the error in the blood input function. Computer simulations show that analytical expressions we derive are sufficiently close to results obtained from numerical methods. Our findings are important to observe the effect of the blood function on kinetic parameter estimation, but also useful to evaluate various blind methods and observe the dependence of kinetic parameter estimates to certain parts of the blood function.
doi:10.1155/2011/234679
PMCID: PMC2993041  PMID: 21127711
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5.  Comparison of radiolabeled isatin analogs for imaging apoptosis with positron emission tomography 
Chen, Delphine L. | Zhou, Dong | Chu, Wenhua | Herrbrich, Phillip E. | Jones, Lynne A. | Rothfuss, Justin M | Engle, Jacquelyn T. | Geraci, Marco | Welch, Michael J. | Mach, Robert H.
Nuclear medicine and biology  2009;36(6):651-658.
Introduction
Caspase-3 is one of the executioner caspases activated as a result of apoptosis. Radiolabeled isatins bind to caspase-3 with high affinity and are potential tracers for use with positron emission tomography to image apoptosis. We compared the ability of 2 novel radiolabeled isatins, [18F]WC-IV-3 and [11C]WC-98, to detect caspase-3 activation in a rat model of cycloheximide-induced liver injury.
Methods
Male Sprague-Dawley rats were treated with cycloheximide and then imaged with microPET 3 hours later with [18F]WC-IV-3 and [11C]WC-98. Biodistribution studies were also performed simultaneously, with caspase-3 activation verified by fluorometric enzyme assay and Western blots.
Results
MicroPET imaging studies demonstrated similar behavior of both tracers but with a lower maximum peak with [11C]WC-98 than with [18F]WC-IV-3. Biodistribution studies demonstrated increased uptake of both tracers in the liver and spleen, but this was statistically significant only in the liver with both compounds. The level of [18F]WC-IV-3 uptake appeared to correlate roughly with rates of caspase-3 activation by the enzyme assay, but the magnitude of difference between treated and control groups was lower than that observed in previously published data with [18F]WC-II-89, another radiolabeled isatin analog. Activation was also confirmed in the liver and spleen but not in fat by Western blot.
Conclusion
[18F]WC-IV-3 uptake appears to correlate with increased caspase-3 enzyme activity, but the dynamic range of uptake of these 2 tracers appears to be less than that seen with [18F]WC-II-89. Studies are ongoing to verify these results in other animal models of apoptosis.
doi:10.1016/j.nucmedbio.2009.03.008
PMCID: PMC2741397  PMID: 19647171
apoptosis; caspase-3; positron emission tomography; radiolabeled isatins; liver injury
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6.  [18F]Ciprofloxacin, a New Positron Emission Tomography Tracer for Noninvasive Assessment of the Tissue Distribution and Pharmacokinetics of Ciprofloxacin in Humans 
Brunner, Martin | Langer, Oliver | Dobrozemsky, Georg | Müller, Ulrich | Zeitlinger, Markus | Mitterhauser, Markus | Wadsak, Wolfgang | Dudczak, Robert | Kletter, Kurt | Müller, Markus
Antimicrobial Agents and Chemotherapy  2004;48(10):3850-3857.
The biodistribution and pharmacokinetics of the fluorine-18-labeled fluoroquinolone antibiotic [18F]ciprofloxacin in tissue were studied noninvasively in humans by means of positron emission tomography (PET). Special attention was paid to characterizing the distribution of [18F]ciprofloxacin to select target tissues. Healthy volunteers (n = 12) were orally pretreated for 5 days with therapeutic doses of unlabeled ciprofloxacin. On day 6, subjects received a tracer dose (mean injected amount, 700 ± 55 MBq, which contained about 0.6 mg of unlabeled ciprofloxacin) of [18F]ciprofloxacin as an intravenous bolus. Thereafter, PET imaging and venous blood sampling were initiated. Time-radioactivity curves were measured for liver, kidney, lung, heart, spleen, skeletal muscle, and brain tissues for up to 6 h after radiotracer administration. The first application of [18F]ciprofloxacin in humans has demonstrated the safety and utility of the newly developed radiotracer for pharmacokinetic PET imaging of the tissue ciprofloxacin distribution. Two different tissue compartments of radiotracer distribution could be identified. The first compartment including the kidney, heart, and spleen, from which the radiotracer was washed out relatively quickly (half-lives [t1/2s], 68, 57, and 106 min, respectively). The second compartment comprised liver, muscle, and lung tissue, which displayed prolonged radiotracer retention (t1/2, >130 min). The highest concentrations of radioactivity were measured in the liver and kidney, the main organs of excretion (standardized uptake values [SUVs], 4.9 ± 1.0 and 9.9 ± 4.4, respectively). The brain radioactivity concentrations were very low (<1 kBq · g−1) and could therefore not be quantified. Transformation of SUVs into absolute concentrations (in micrograms per milliliter) allowed us to relate the concentrations at the target site to the susceptibilities of bacterial pathogens. In this way, the frequent use of ciprofloxacin for the treatment of a variety of infections could be corroborated.
doi:10.1128/AAC.48.10.3850-3857.2004
PMCID: PMC521875  PMID: 15388445
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7.  Positron Emission Tomography Imaging of Regional Pulmonary Perfusion and Ventilation 
Musch, Guido | Venegas, Jose G.
Proceedings of the American Thoracic Society  2005;2(6):522-527.
Positron emission tomography (PET) imaging is a noninvasive, quantitative method to assess pulmonary perfusion and ventilation in vivo. The core of this article focuses on the use of [13N]nitrogen (13N2) and PET to assess regional gas exchange. Regional perfusion and shunt can be measured with the 13N2–saline bolus infusion technique. A bolus of 13N2, dissolved in saline solution, is injected intravenously at the start of a brief apnea, while the tracer kinetics in the lung is measured by a sequence of PET frames. Because of its low solubility in blood, virtually all 13N2 delivered to aerated lung regions diffuses into the alveolar airspace, where it accumulates in proportion to regional perfusion during the apnea. In contrast, lung regions that are perfused but are not aerated and do not exchange gas (i.e., “shunting” units) do not retain 13N2 during apnea and the tracer concentration drops after the initial peak. Accurate estimates of regional perfusion and regional shunt can be derived by applying a mathematical model to the pulmonary kinetics of a 13N2–saline bolus. When breathing is resumed, specific alveolar ventilation can be calculated from the tracer washout rate, because 13N2 is eliminated almost exclusively by ventilation. Because of the rapid elimination of the tracer, 13N2 infusion scans can be followed by 13N2 inhalation scans that allow determination of regional gas fraction. This article describes insights into the pathophysiology of acute lung injury, pulmonary embolism, and asthma that have been gained by PET imaging of regional gas exchange.
doi:10.1513/pats.200508-088DS
PMCID: PMC2713340  PMID: 16352758
adult respiratory distress syndrome; asthma; emission-computed tomography; nitrogen isotopes; pulmonary embolism; pulmonary gas exchange
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8.  Utility of 3’-[18F]fluoro-3’-deoxythymidine as a PET tracer to monitor response to gene therapy in a xenograft model of head and neck carcinoma 
Mason, Neale S | Lopresti, Brian J | Ruszkiewicz, James | Dong, Xinxin | Joyce, Sonali | Leef, George | Sen, Malabika | Wahed, Abdus S | Mathis, Chester A | Grandis, Jennifer R | Thomas, Sufi M
American Journal of Nuclear Medicine and Molecular Imaging  2013;3(1):16-31.
Noninvasive imaging methodologies are needed to assess treatment responses to novel molecular targeting approaches for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Computer tomography and magnetic resonance imaging do not effectively distinguish tumors from fibrotic tissue commonly associated with SCCHN tumors. Positron emission tomography (PET) offers functional non-invasive imaging of tumors. We determined the uptake of the PET tracers 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 3’-[18F]Fluoro-3’-deoxythymidine ([18F]FLT) in several SCCHN xenograft models. In addition, we evaluated the utility of [18F]FLT microPET imaging in monitoring treatment response to an EGFR antisense approach targeted therapy that has shown safety and efficacy in a phase I trial. Two of the 3 SCCHN xenograft models tested demonstrated no appreciable uptake or retention of [18F]FDG, but consistent accumulation of [18F]FLT. The third tumor xenograft SCCHN model (Cal33) demonstrated variable uptake of both tracers. SCCHN xenografts (1483) treated with EGFR antisense gene therapy decreased tumor volumes in 4/6 mice. Reduced uptake of [18F]FLT was observed in tumors that responded to epidermal growth factor antisense (EGFRAS) gene therapy compared to non-responding tumors or tumors treated with control sense plasmid DNA. These findings indicate that [18F]FLT PET imaging may be useful in monitoring SCCHN response to molecular targeted therapies, while [18F]FDG uptake in SCCHN xenografts may not be reflective of the level of metabolic activity characteristic of human SCCHN tumors.
PMCID: PMC3545366  PMID: 23342298
Squamous cell carcinoma of the head and neck (SCCHN); positron emission tomography (PET); 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG); 3’-[18F]Fluoro-3’-deoxythymidine ([18F]FLT); epidermal growth factor receptor (EGFR); volume of interest (VOI); standardize uptake values (SUV); region of interest (ROI)
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9.  Nonlinear Model for Capillary-Tissue Oxygen Transport and Metabolism 
Li, Zheng | Yipintsoi, Tada | Bassingthwaighte, James B.
Annals of biomedical engineering  1997;25(4):604-619.
Oxygen consumption in small tissue regions cannot be measured directly, but assessment of oxygen transport and metabolism at the regional level is possible with imaging techniques using tracer 15O-oxygen for positron emission tomography. On the premise that mathematical modeling of tracer kinetics is the key to the interpretation of regional concentration-time curves, an axially-distributed capillary-tissue model was developed that accounts for oxygen convection in red blood cells and plasma, nonlinear binding to hemoglobin and myoglobin, transmembrane transport among red blood cells, plasma, interstitial fluid and parenchymal cells, axial dispersion, transformation to water in the tissue, and carriage of the reaction product into venous effluent. Computational speed was maximized to make the model useful for routine analysis of experimental data. The steady-state solution of a parent model for nontracer oxygen governs the solutions for parallel-linked models for tracer oxygen and tracer water. The set of models provides estimates of oxygen consumption, extraction, and venous pO2 by fitting model solutions to experimental tracer curves of the regional tissue content or venous outflow. The estimated myocardial oxygen consumption for the whole heart was in good agreement with that measured directly by the Fick method and was relatively insensitive to noise. General features incorporated in the model make it widely applicable to estimating oxygen consumption in other organs from data obtained by external detection methods such as positron emission tomography.
PMCID: PMC3589573  PMID: 9236974
Nonlinear modeling; Convection; Diffusion; Permeation; Binding; Metabolic reaction; Heart; Myocardial blood flow; Heterogeneity; PET
Related Articles
10.  Modelling and Detecting Tumour Oxygenation Levels 
Skeldon, Anne C. | Chaffey, Gary | Lloyd, David J. B. | Mohan, Vineet | Bradley, David A. | Nisbet, Andrew | Secomb, Timothy W.
PLoS ONE  2012;7(6):e38597.
Tumours that are low in oxygen (hypoxic) tend to be more aggressive and respond less well to treatment. Knowing the spatial distribution of oxygen within a tumour could therefore play an important role in treatment planning, enabling treatment to be targeted in such a way that higher doses of radiation are given to the more radioresistant tissue. Mapping the spatial distribution of oxygen in vivo is difficult. Radioactive tracers that are sensitive to different levels of oxygen are under development and in the early stages of clinical use. The concentration of these tracer chemicals can be detected via positron emission tomography resulting in a time dependent concentration profile known as a tissue activity curve (TAC). Pharmaco-kinetic models have then been used to deduce oxygen concentration from TACs. Some such models have included the fact that the spatial distribution of oxygen is often highly inhomogeneous and some have not. We show that the oxygen distribution has little impact on the form of a TAC; it is only the mean oxygen concentration that matters. This has significant consequences both in terms of the computational power needed, and in the amount of information that can be deduced from TACs.
doi:10.1371/journal.pone.0038597
PMCID: PMC3386285  PMID: 22761687
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11.  Nonparametric Residue Analysis of Dynamic PET Data With Application to Cerebral FDG Studies in Normals 
O'Sullivan, Finbarr | Muzi, Mark | Spence, Alexander M. | Mankoff, David M. | O'Sullivan, Janet N. | Fitzgerald, Niall | Newman, George C. | Krohn, Kenneth A.
Journal of the American Statistical Association  2009;104(486):556-571.
Kinetic analysis is used to extract metabolic information from dynamic positron emission tomography (PET) uptake data. The theory of indicator dilutions, developed in the seminal work of Meier and Zierler (1954), provides a probabilistic framework for representation of PET tracer uptake data in terms of a convolution between an arterial input function and a tissue residue. The residue is a scaled survival function associated with tracer residence in the tissue. Nonparametric inference for the residue, a deconvolution problem, provides a novel approach to kinetic analysis—critically one that is not reliant on specific compartmental modeling assumptions. A practical computational technique based on regularized cubic B-spline approximation of the residence time distribution is proposed. Nonparametric residue analysis allows formal statistical evaluation of specific parametric models to be considered. This analysis needs to properly account for the increased flexibility of the nonparametric estimator. The methodology is illustrated using data from a series of cerebral studies with PET and fluorodeoxyglucose (FDG) in normal subjects. Comparisons are made between key functionals of the residue, tracer flux, flow, etc., resulting from a parametric (the standard two-compartment of Phelps et al. 1979) and a nonparametric analysis. Strong statistical evidence against the compartment model is found. Primarily these differences relate to the representation of the early temporal structure of the tracer residence—largely a function of the vascular supply network. There are convincing physiological arguments against the representations implied by the compartmental approach but this is the first time that a rigorous statistical confirmation using PET data has been reported. The compartmental analysis produces suspect values for flow but, notably, the impact on the metabolic flux, though statistically significant, is limited to deviations on the order of 3%–4%. The general advantage of the nonparametric residue analysis is the ability to provide a valid kinetic quantitation in the context of studies where there may be heterogeneity or other uncertainty about the accuracy of a compartmental model approximation of the tissue residue.
doi:10.1198/jasa.2009.0021
PMCID: PMC2760850  PMID: 19830267
Deconvolution; Functional inference; Kinetic analysis; Regularization
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12.  Single-scan dual-tracer FLT+FDG PET tumor characterization 
Kadrmas, Dan J | Rust, Thomas C | Hoffman, John M
Physics in medicine and biology  2013;58(3):429-449.
Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems—both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10–60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), Knet, and K1 as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k2, k3) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging.
doi:10.1088/0031-9155/58/3/429
PMCID: PMC3553659  PMID: 23296314
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13.  Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study 
Bruijnen, Stefan TG | van der Weijden, Mignon AC | Klein, Joannes P | Hoekstra, Otto S | Boellaard, Ronald | van Denderen, J Christiaan | Dijkmans, Ben AC | Voskuyl, Alexandre E | van der Horst-Bruinsma, Irene E | van der Laken, Conny J
Arthritis Research & Therapy  2012;14(2):R71.
Introduction
Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [18F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference.
Methods
In a stepwise approach different PET tracers were investigated. First, whole body [18F]FDG and [11C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [18F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data.
Results
No increased [18F]FDG and [11C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [18F]Fluoride PET-CT, [18F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [18F]FDG depicted only three lesions, with an uptake of five times lower compared to [18F]Fluoride, and again no [11C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [18F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [18F]Fluoride PET positive lesions.
Conclusions
Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [18F]Fluoride. In contrast to active RA, inflammation tracers [18F]FDG and [11C](R)PK11195 appeared to be less useful for AS imaging.
doi:10.1186/ar3792
PMCID: PMC3446444  PMID: 22471910
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14.  Tracer input for kinetic modelling of liver physiology determined without sampling portal venous blood in pigs 
Winterdahl, Michael | Keiding, Susanne | Sørensen, Michael | Mortensen, Frank Viborg | Alstrup, Aage Kristian Olsen | Munk, Ole Lajord
European Journal of Nuclear Medicine and Molecular Imaging  2010;38(2):263-270.
Purpose
Quantification of hepatic tracer kinetics by PET requires measurement of tracer input from the hepatic artery (HA) and portal vein (PV). We wished to develop a method for estimating dual tracer input without the necessity to sample PV blood.
Methods
Pigs weighing 40 kg were given bolus doses of C15O (CO), 2-[18F]fluoro-2-deoxy-D-glucose (FDG), [11C]-methylglucose (MG), 2-[18F]fluoro-2-deoxy-D-galactose (FDGal) or H215O (H2O). Tracer concentration 3-min time courses were measured in the femoral artery and PV by blood sampling. Blood flow was measured in the HA and PV using flow-meters. A model for transfer of tracer through the splanchnic circulation was used to estimate values of a tracer-specific model parameter β. Tracer-specific mean values of β were used to estimate tracer concentration time courses in the PV from the measured arterial concentration. A model-derived dual-input was calculated using the mean HA flow fraction (0.25) and validated by comparison of the use of the measured dual-input and a kinetic model with a fixed ”true” K1true, i.e. clearance of tracer from blood to liver cells.
Results
The rank order of the means of β was CO < FDG ≈ MG < FDGal < H2O, reflecting their different splanchnic mean transit times. Estimated K1est was not significantly different from “true” K1true.
Conclusion
The hepatic dual tracer input, which is of great importance for the assessment of processes such as transfer across the plasma-hepatocyte membrane or hepatic blood perfusion, can be well approximated in pigs without the necessity to sample PV blood and measure hepatic blood flow; only arterial blood sampling is needed.
doi:10.1007/s00259-010-1620-0
PMCID: PMC3021702  PMID: 20882283
Splanchnic circulation; Liver kinetics; Molecular imaging; Pharmacokinetics; PET; Portal model; Radioactive tracers
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15.  Tracer input for kinetic modelling of liver physiology determined without sampling portal venous blood in pigs 
Winterdahl, Michael | Keiding, Susanne | Sørensen, Michael | Mortensen, Frank Viborg | Alstrup, Aage Kristian Olsen | Munk, Ole Lajord
European journal of nuclear medicine and molecular imaging  2010;38(2):263-270.
Purpose
Quantification of hepatic tracer kinetics by PET requires measurement of tracer input from the hepatic artery (HA) and portal vein (PV). We wished to develop a method for estimating dual tracer input without the necessity to sample PV blood.
Methods
Pigs weighing 40 kg were given bolus doses of C15O (CO), 2-[18F]fluoro-2-deoxy-d-glucose (FDG), [11C]-methylglucose (MG), 2-[18F]fluoro-2-deoxy-d-galactose (FDGal) or H2 15O (H2O). Tracer concentration 3-min time courses were measured in the femoral artery and PV by blood sampling. Blood flow was measured in the HA and PV using flow-meters. A model for transfer of tracer through the splanchnic circulation was used to estimate values of a tracer-specific model parameter β. Tracer-specific mean values of β were used to estimate tracer concentration time courses in the PV from the measured arterial concentration. A model-derived dual-input was calculated using the mean HA flow fraction (0.25) and validated by comparison of the use of the measured dual-input and a kinetic model with a fixed “true” K1true, i.e. clearance of tracer from blood to liver cells.
Results
The rank order of the means of β was CO
Conclusion
The hepatic dual tracer input, which is of great importance for the assessment of processes such as transfer across the plasma-hepatocyte membrane or hepatic blood perfusion, can be well approximated in pigs without the necessity to sample PV blood and measure hepatic blood flow; only arterial blood sampling is needed.
doi:10.1007/s00259-010-1620-0
PMCID: PMC3021702  PMID: 20882283
Splanchnic circulation; Liver kinetics; Molecular imaging; Pharmacokinetics; PET; Portal model; Radioactive tracers
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Winant, Celeste D | Aparici, Carina Mari | Zelnik, Yuval R | Reutter, Bryan W | Sitek, Arkadiusz | Bacharach, Stephen L | Gullberg, Grant T
Physics in Medicine and Biology  2011;57(2):375-393.
Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic 94Tc-methoxyisobutylisonitrile (94Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K1 for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K1. For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from 94Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of 99mTc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal maximum-likelihood expectation-maximization (4D ML-EM) reconstructions gave more accurate reconstructions than did standard frame-by-frame static 3D ML-EM reconstructions. The SPECT/P results showed that 4D ML-EM reconstruction gave higher and more accurate estimates of K1 than did 3D ML-EM, yielding anywhere from a 44% underestimation to 24% overestimation for the three patients. The SPECT/D results showed that 4D ML-EM reconstruction gave an overestimation of 28% and 3D ML-EM gave an underestimation of 1% for K1. For the patient study the 4D ML-EM reconstruction provided continuous images as a function of time of the concentration in both ventricular cavities and myocardium during the 2 min infusion. It is demonstrated that a 2 min infusion with a two-headed SPECT system rotating 180° every 54 s can produce measurements of blood pool and myocardial TACs, though the SPECT simulation studies showed that one must sample at least every 30 s to capture a 1 min infusion input function.
doi:10.1088/0031-9155/57/2/375
PMCID: PMC3325151  PMID: 22170801
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Razifar, Pasha | Hennings, Joakim | Monazzam, Azita | Hellman, Per | Långström, Bengt | Sundin, Anders
BMC Medical Imaging  2009;9:6.
Background
In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality.
Methods
In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0–45 minutes after the tracer injection, was used to study the tracer pharmacokinetics.
Results
Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15–45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining "hot spot" regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from "50% cut-off" ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment.
Conclusion
In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET measurements, for instance in therapy monitoring as well as for delineation of the tumour in radiation therapy planning.
doi:10.1186/1471-2342-9-6
PMCID: PMC2680831  PMID: 19386097
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Wang, Z. Jane | Szabo, Zsolt | Lei, Peng | Varga, József | Liu, K. J. Ray
IEEE transactions on signal processing : a publication of the IEEE Signal Processing Society  2008;53(9):3473-3487.
The positron emission tomography (PET) imaging technique enables the measurement of receptor distribution or neurotransmitter release in the living brain and the changes of the distribution with time and thus allows quantification of binding sites as well as the affinity of a radioligand. However, quantification of receptor binding studies obtained with PET is complicated by tissue heterogeneity in the sampling image elements (i.e., voxels, pixels). This effect is caused by a limited spatial resolution of the PET scanner. Spatial heterogeneity is often essential in understanding the underlying receptor binding process. Tracer kinetic modeling also often requires an intrusive collection of arterial blood samples. In this paper, we propose a likelihood-based framework in the voxel domain for quantitative imaging with or without the blood sampling of the input function. Radioligand kinetic parameters are estimated together with the input function. The parameters are initialized by a subspace-based algorithm and further refined by an iterative likelihood-based estimation procedure. The performance of the proposed scheme is examined by simulations. The results show that the proposed scheme provides reliable estimation of factor time-activity curves (TACs) and the underlying parametric images. A good match is noted between the result of the proposed approach and that of the Logan plot. Real brain PET data are also examined, and good performance is observed in determining the TACs and the underlying factor images.
doi:10.1109/TSP.2005.853149
PMCID: PMC2185066  PMID: 18769527
Brain receptor study; compartmental model; distribution volume; dynamic imaging; likelihood; PET; tracer kinetic modeling; voxel-domain quantitative imaging
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Rudnicki, P | Mikolajczyk, K | Grodzki, M | Burger, C
Journal of Medical Internet Research  1999;1(suppl1):e77.
Introduction
Kinetic modeling is the method of choice for assessing the behaviour of new PET (Positron Emission Tomography) tracers. For suitable tracers, kinetic models allow to derive unique functional information from the acquired PET data, for instance the absolute perfusion or the density of specific receptors in brain tissue. However, the processing steps required are sophisticated. As there has no comprehensive modeling software been available in the past, kinetic models could only be developed and applied by a limited number of sites. This paper presents such a software package called PMOD. Being developed with Internet technologies it can easily be distributed and may thus help consolidate more widespread use of kinetic modeling.
Methods
Aiming at maximal portability, the entire software was programmed in Java 2. An interface was defined such that new models can easily and seamlessly be added by a sort of plug-in programming. It is general enough to cope with virtually all models published so far. Innovative models may therefore directly be implemented in PMOD, or they may easily be incorporated even by external researchers. The supported features include weighted least squares fitting, parameter coupling among models, Monte Carlo simulations for assessing parameter identifiability, and batch processing for scheduling a sequence of time-consuming trials. The software can be configured as a local JAVA application, but can also be installed on an Internet server and be run from any Java2-enabled WWW-browser.
Results
The modeling software currently supports 19 different models ranging from simple tissue ratio methods to complex multi-injection protocols with two input curves plus metabolite correction. It has been tested on different platforms such as HP-UX, Sun Solaris, Linux, and Windows. At present it has been adopted by 7 sites which run the software on PC/NT. Experiences on this platform demonstrate:
The Java Virtual Machine runs with high reliability.
Despite just-in-time compilation there still exists a significant performance penalty for Java applications, especially with respect to memory management.
The kinetic modeling environment in its present form is used on a daily basis at several sites for scientific studies and even for some types of clinical studies.
Discussion
Earlier kinetic modeling programs were typically based on high-level languages such as Matlab or IDL and tailored to the need of individual sites. Every attempt to port them to a different environment was a major undertaking. This is in contrast to the present modeling software which runs on any platform as an application and supports easy data input.
Acknowledgement:
This work was supported by the Swiss National Science Foundation, Project 7PLPJ048289.
doi:10.2196/jmir.1.suppl1.e77
PMCID: PMC1761818
Medical Informatics Applications; PET; Kinetic Modeling; Java
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Sørensen, Michael | Mikkelsen, Kasper Sandager | Frisch, Kim | Bass, Ludvik | Bibby, Bo Martin | Keiding, Susanne
Journal of nuclear medicine : official publication, Society of Nuclear Medicine  2011;52(10):1566-1572.
Accurate quantification of regional liver function is needed, and PET of specific hepatic metabolic pathways offers a unique method for this purpose. Here, we quantify hepatic galactose elimination in humans using PET and the galactose analog 2-18F-fluoro-2-deoxy-d-galactose (18F-FDGal) as the PET tracer.
Methods
Eight healthy human subjects underwent 18F-FDGal PET/CT of the liver with and without a simultaneous infusion of galactose. Hepatic systemic clearance of 18F-FDGal was determined from linear representation of the PET data. Hepatic galactose removal kinetics were determined using measurements of hepatic blood flow and arterial and liver vein galactose concentrations at increasing galactose infusions. The hepatic removal kinetics of 18F-FDGal and galactose and the lumped constant (LC) were determined.
Results
The mean hepatic systemic clearance of 18F-FDGal was significantly higher in the absence than in the presence of galactose (0.274 ± 0.001 vs. 0.019 ± 0.001 L blood/min/L liver tissue; P < 0.01), showing competitive substrate inhibition of galactokinase. The LC was 0.13 ± 0.01, and the 18F-FDGal PET with galactose infusion provided an accurate measure of the local maximum removal rate of galactose (Vmax) in liver tissue compared with the Vmax estimated from arterio-liver venous (A-V) differences (1.41 ± 0.24 vs. 1.76 ± 0.08 mmol/min/L liver tissue; P = 0.60). The first-order hepatic systemic clearance of 18F-FDGal was enzyme-determined and can thus be used as an indirect estimate of galactokinase capacity without the need for galactose infusion or knowledge of the LC.
Conclusion
18F-FDGal PET/CT provides an accurate in vivo measurement of human galactose metabolism, which enables the quantification of regional hepatic metabolic function.
doi:10.2967/jnumed.111.092924
PMCID: PMC3407686  PMID: 21875925
hepatic metabolic function; galactose metabolism; Michaelis–Menten kinetics; molecular imaging; nuclear hepatology
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Wang, Guobao | Qi, Jinyi
IEEE transactions on medical imaging  2009;28(4):608-620.
Quantification of tracer kinetics using dynamic positron emission tomography (PET) provides important information for understanding the physiological and biochemical processes in humans and animals. A common procedure is to reconstruct a sequence of dynamic images first, and then apply kinetic analysis to the time activity curve of a region of interest derived from the reconstructed images. Obviously, the choice of image reconstruction method and its parameters affect the accuracy of the time activity curve and hence the estimated kinetic parameters. This paper analyzes the effects of penalized likelihood image reconstruction on tracer kinetic parameter estimation. Approximate theoretical expressions are derived to study the bias, variance, and ensemble mean squared error of the estimated kinetic parameters. Computer simulations show that these formulae predict correctly the changes of these statistics as functions of the regularization parameter. It is found that the choice of the regularization parameter has a significant impact on kinetic parameter estimation, indicating proper selection of image reconstruction parameters is important for dynamic PET. A practical method has been developed to use the theoretical formulae to guide the selection of the regularization parameter in dynamic PET image reconstruction.
doi:10.1109/TMI.2008.2008971
PMCID: PMC2792209  PMID: 19211345
Image reconstruction; penalized maximum likelihood; tracer kinetic modeling; noise analysis
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Peng, Fangyu | Lutsenko, Svetlana | Sun, Xiankai | Muzik, Otto
Molecular Imaging and Biology  2012;14(1):70-78.
Purpose
This study aims to determine feasibility and utility of copper-64(II) chloride (64CuCl2) as a tracer for positron emission tomography (PET) of copper metabolism imbalance in human Wilson’s disease (WD).
Procedures
Atp7b−/− mice, a mouse model of human WD, were injected with 64CuCl2 intravenously and subjected to PET scanning using a hybrid PET-CT (computerized tomography) scanner, with the wild-type C57BL mice as a normal control. Quantitative PET analysis was performed to determine biodistribution of 64Cu radioactivity and radiation dosimetry estimates of 64Cu were calculated for PET of copper metabolism in humans.
Results
Dynamic PET analysis revealed increased accumulation and markedly reduced clearance of 64Cu from the liver of the Atp7b−/− mice, compared to hepatic uptake and clearance of 64Cu in the wild-type C57BL mice. Kinetics of copper clearance and retention was also altered for kidneys, heart, and lungs in the Atp7b−/− mice. Based on biodistribution of 64Cu in wild-type C57BL mice, radiation dosimetry estimates of 64Cu in normal human subjects were obtained, showing an effective dose (ED) of 32.2 μ (micro)Sv/MBq (weighted dose over 22 organs) and the small intestine as the critical organ for radiation dose (61 μGy/MBq for males and 69 μGy/MBq for females). Radiation dosimetry estimates for the patients with WD, based on biodistribution of 64Cu in the Atp7b−/− mice, showed a similar ED of 32.8 μ (micro)Sv/MBq (p= 0.53), with the liver as the critical organ for radiation dose (120 μSv/MBq for male and 161 μSv/MBq for female).
Conclusions
Quantitative PET analysis demonstrates abnormal copper metabolism in the mouse model of WD with improved time–resolution. Human radiation dosimetry estimates obtained in this preclinical study encourage direct radiation dosimetry of 64CuCl2 in human subjects. The results suggest feasibility of utilizing 64CuCl2 as a tracer for noninvasive assessment of copper metabolism in WD with PET.
doi:10.1007/s11307-011-0476-4
PMCID: PMC3157550  PMID: 21327972
Copper metabolism; Wilson’s disease; ATP7B copper transporter; Positron emission tomography; Copper-64 (II) chloride; Radiation dosimetry
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Paul, A.K. | Lobarinas, E. | Simmons, R. | Wack, D. | Luisi, John C. | Spernyak, J. | Mazurchuk, R | Abdel-Nabi, H. | Salvi, R.
NeuroImage  2008;44(2):312-318.
Although much is known about the perceptual characteristics of tinnitus, its neural origins remain poorly understood. We investigated the pattern of neural activation in central auditory structures using positron emission tomography (PET) imaging in a rat model of salicylate-induced tinnitus. Awake rats were injected with the metabolic tracer, fluorine-18 fluorodeoxyglucose (FDG), once in a quiet state (baseline) and once during salicylate-induced tinnitus. Tinnitus was verified using a behavioral technique. Brain imaging was performed using a high-resolution microPET scanner. Rats underwent magnetic resonance imaging (MRI) and reconstructed MRI and microPET images were fused to identify brain structures. FDG activity in brain regions of interest were quantified and compared. MicroPET imaging showed that FDG activity in the frontal pole was stable between baseline and tinnitus conditions, suggesting it was metabolically inert during tinnitus. Inferior colliculi (p=0.03) and temporal cortices (p=0.003) showed significantly increased FDG activity during tinnitus relative to baseline; activity in the colliculi and temporal cortices increased by 17% ± 21% and 29% ± 20%, respectively. FDG activity in the thalami also increased during tinnitus, but the increase did not reach statistical significance (p=0.07). Our results show increased metabolic activity consistent with neuronal activation in inferior colliculi and auditory cortices of rats during salicylate-induced tinnitus. These results are the first to show that microPET imaging can be used to identify central auditory structures involved in tinnitus and suggest that microPET imaging might be used to evaluate the therapeutic potential of drugs to treat tinnitus.
doi:10.1016/j.neuroimage.2008.09.02
PMCID: PMC2613016  PMID: 18948211
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Simoncic, Urban | Jeraj, Robert
Journal of Cerebral Blood Flow & Metabolism  2010;31(2):750-756.
Compartmental modeling and spectral analysis are often used for tracer kinetic modeling in positron emission tomography (PET). The concentrations in kinetic equations are usually considered to be instantaneous, whereas PET data are inherently integrated over time, which leads to uncertainties in the results. A new formalism for kinetic analysis that uses cumulative tracer concentrations and avoids approximating the image-derived input function and PET measurements with midframe instantanous values was developed. We assessed the improvements of the new formalism over the midframe approximation methods for three commonly used radiopharmaceuticals: [11C]raclopride, 2′-deoxy-2′-[18F]fluoro--glucose (FDG), and 3′-deoxy-3′-[18F]fluoro-thymidine (FLT). We found that improvements are case dependent and often not negligible. Improvements for determination of binding potential for [11C]raclopride ranged from 5% to 25%. Improvements in estimation accuracy of FDG and FLT microparameters ranged up to 25%. On the other hand, estimation of macroparameter Ki=K1k3/(k2+k3) for FDG or FLT did not show significant benefit with the new method; only modest improvement up to 2% was observed. Assessment of the benefits of using new method is far from being exhaustive, but possibly significant improvement was demonstrated. Therefore, we consider the proposed algorithm a necessary component of any kinetic analysis software.
doi:10.1038/jcbfm.2010.159
PMCID: PMC3049528  PMID: 20808319
compartmental models; kinetic analysis; positron emission tomography; raclopride; tracer kinetics
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Tantawy, Mohammed N. | Jones, Carrie K. | Baldwin, Ronald M. | Ansari, M. Sib | Conn, P. Jeffrey | Kessler, Robert M. | Peterson, Todd E.
Nuclear medicine and biology  2009;36(8):931-940.
[18F]fallypride PET studies can be used to estimate the non-displaceable binding potential (BPND) in vivo of dopamine D2/D3 receptor-rich regions of the brain. These studies often take considerable time, up to two or more hours, limiting the throughput. In this work, we investigated whether limited-duration scans performed subsequent to tracer administration yielded stable BPND estimates. In particular, we applied a modified version of the Logan plot method on the last 60 min of 120 min data and compared the results to those from analysis of the full data set.
Methods
Fourteen male Sprague-Dawley rats were injected with [18F]fallypride intravenously while under isoflurane anesthesia and dynamic data were acquired on the microPET Focus 220 for 120 min. The distribution volume ratio (DVR = BPND + 1) was calculated from a Logan plot using 120 min of data and from a modified version using only the last 60 min. Three of these rats were imaged again on a second day to test the reproducibility. A two-tissue compartment model also was used to fit the time activity curves (TACs) of the 120 min scans to estimate the parameters K1, k2, kon, k4, and Bmax. These parameters then were used to simulate similar TACs while changing kon to reflect changes in the dopaminergic system. The simulated TACs were used as a means for exploring the differences in DVR estimates between the last 60 min only and the full 120 min of simulated data.
Results
The average DVR from the full 120 min scans was 13.8 ± 0.9 whereas the average distribution volume ratio estimated from only the last 60 min of data (DVR′) was 16.3 ± 1.0. The distribution volume ratio estimates showed good reproducibility in the three rats (mean DVR = 13.8 ± 1.5 on Day 1 and DVR = 13.8 ± 0.9 on Day 2). The simulations showed that the relationship between DVR′ and DVR estimates follows a semi-linear form with varying kon.
Conclusion
Although the BPND estimates are slightly overestimated in a delayed scan mode (i.e. no initial radiotracer uptake measurements) compared to a full scan, this overestimation depends primarily on k3 (≈ kon × Bmax) and has been evaluated in this work for a wide range of kon values using simulated TACs. In particular, the sensitivity of DVR′ to changes in kon is similar to that of DVR. This method of delayed scans eliminates the necessity of imaging during the initial uptake of the radiotracer and, thus, can be used to increase the throughput of studies.
doi:10.1016/j.nucmedbio.2009.06.007
PMCID: PMC2771119  PMID: 19875049
18F-fallypride; dopamine receptors; graphical analysis; kinetic modeling; microPET
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