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Paul D Acton

Publications and source records attributed to Paul D Acton.

At least 19 recordsLinked to original sources
PubMed2006

Analytical derivation of the point spread function for pinhole collimators.

The point spread function (PSF) of a pinhole collimator plays an important role in determining the resolution and characterizing the sensitivity of the accepted photons from a given point in the image space. The focus of this paper is to derive an analytical expression for the PSF of two different types of focusing pinhole collimators that are based on (1) right-circular double cones and (2) oblique-circular double cones. Conventionally, focusing pinhole collimators used in multi-pinhole SPECT were designed using right-circular double cones, as they were easier to fabricate. In this work, a novel focusing collimator consisting of oblique-circular double cones was designed and its properties were studied in detail with respect to right-circular double-cone based collimators. The main advantage of determining the PSF is the fact that they can be used to accurately model the PSF during the reconstruction, thereby improving the resolution of the reconstructed image. The PSF of the focusing collimators based on oblique-circular cones were found to be almost shift invariant for low and medium energy photons (below 200 keV). This property is very advantageous as algorithms such as slice-by-slice reconstruction can be used for resolution recovery thereby drastically reducing the reconstruction time. However, the PSF of focusing oblique-circular double cones (FOCDC) for higher energy photons were found to be asymmetric and hence need to be modelled more accurately during the reconstruction. On the other hand, the PSF for the right-circular cone based collimators were found to be asymmetric for all energy levels. However, due to the smaller acceptance angle used, the number of penetration photons was found to be far less than that observed for oblique-circular cones. This results in a smaller PSF making right-circular cone based collimators preferable for high-resolution small animal imaging, especially where very small pinhole diameters are used. The analytically derived PSF for both collimators were validated using a ray-tracing based Monte Carlo approach and found to agree well with a mean square error of less than 1%.

Algorithms↗
PubMed2006

Artificial neural network classifier for the diagnosis of Parkinson's disease using [99mTc]TRODAT-1 and SPECT.

Imaging the dopaminergic neurotransmitter system with positron emission tomography (PET) or single photon emission tomography (SPECT) is a powerful tool for the diagnosis of Parkinson's disease (PD). Previous studies have indicated that human observers have a diagnostic accuracy similar to conventional ROI analysis of SPECT imaging data. Consequently, it has been hypothesized that an artificial neural network (ANN), which can mimic the pattern recognition skills of human observers, may provide similar results. A set of patients with PD, and normal healthy control subjects, were studied using the dopamine transporter tracer [(99m)Tc]TRODAT-1 and SPECT. The sample was comprised of 81 patients (mean age +/- SD: 63.4 +/- 10.4 years; age range: 39.0-84.2 years) and 94 healthy controls (mean age +/- SD: 61.8 +/- 11.0 years; age range: 40.9-83.3 years). The images were processed to extract the striatum and the striatal pixel values were used as inputs to a three-layer ANN. The same set of data was used to both train and test the ANN, in a 'leave one out' procedure. The diagnostic accuracy of the ANN was higher than any previous analysis method applied to the same data (94.4% total accuracy, 97.5% specificity and 91.4% sensitivity). However, it should be stressed that, as with all applications of an ANN, it was difficult to interpret precisely what triggers in the images were being detected by the network.

Adult↗
PubMed2006

Simplified quantification of small animal [18F]FDG PET studies using a standard arterial input function.

PURPOSE: Arterial input function (AIF) measurement for quantification of small animal PET studies is technically challenging and limited by the small blood volume of small laboratory animals. The present study investigated the use of a standard arterial input function (SAIF) to simplify the experimental procedure. METHODS: Twelve [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET studies accompanied by serial arterial blood sampling were acquired in seven male Sprague-Dawley rats under isoflurane anaesthesia without (every rat) and with additional (five rats) vibrissae stimulation. A leave-one-out procedure was employed to validate the use of a SAIF with individual scaling by one (1S) or two (2S) arterial blood samples. RESULTS: Automatic slow bolus infusion of [(18)F]FDG resulted in highly similar AIF in all rats. The average differences of the area under the curve of the measured AIF and the individually scaled SAIF were 0.11+/-4.26% and 0.04+/-2.61% for the 1S (6-min sample) and the 2S (4-min/43-min samples) approach, respectively. The average differences between the cerebral metabolic rates of glucose (CMR(glc)) calculated using the measured AIF and the scaled SAIF were 1.31+/-5.45% and 1.30+/-3.84% for the 1S and the 2S approach, respectively. CONCLUSION: The use of a SAIF scaled by one or (preferably) two arterial blood samples can serve as a valid substitute for individual AIF measurements to quantify [(18)F]FDG PET studies in rats. The SAIF approach minimises the loss of blood and should be ideally suited for longitudinal quantitative small animal [(18)F]FDG PET studies.

Algorithms↗
PubMed2006

Quantitative imaging of myocardial infarct in rats with high resolution pinhole SPECT.

Small animal imaging of cardiovascular disease using single photon emission tomography (SPECT) can be used to provide quantitative measurements of myocardial infarct. The purpose of this study was to demonstrate the accuracy of pinhole SPECT imaging with [99mTc]sestamibi for estimation of infarct size in a rat model of coronary artery disease. Nine rats had their left anterior descending artery ligated to induce a region of myocardial infarct. These animals were injected with 37 MBq [99mTc]sestamibi, and, 1 h later, scanned on a pinhole SPECT system for 30 min. The defect size measured with SPECT, which was dependent on a threshold applied to the short axis circumferential profiles, was compared against the gold standard triphenyltetrazolium chloride (TTC) staining. The size of the perfusion deficit measured using [99mTc]sestamibi SPECT compared very favorably with the TTC staining result, for threshold values in the range 50-70%. The optimum threshold was approximately 70%, giving an excellent correlation (R2=0.89, p<0.001). Estimation of infarct size by [99mTc] sestamibi SPECT yielded an excellent agreement with TTC staining. In conclusion, measurement of myocardial infarct with SPECT can be used to study the rat heart in vivo, and provides a quantitative measure of myocardial viability.

Animals↗
PubMed2006

Comparison of region-of-interest analysis and human observers in the diagnosis of Parkinson's disease using [99mTc]TRODAT-1 and SPECT.

This study determined the relative accuracy of diagnosis of Parkinson's disease (PD) using SPECT imaging data, comparing a semi-quantitative region-of-interest (ROI) approach and human observers. A set of patients with PD and normal healthy control subjects were studied using the dopamine transporter tracer [(99m)Tc]TRODAT-1 and SPECT. The sample comprised 81 patients (mean age +/- SD, 63.4 +/- 10.4 years; age range, 39.0-84.2 years) and 94 healthy controls (mean age +/- SD, 61.8 +/- 11.0 years; age range, 40.9-83.3 years). A standardized template containing six ROIs was transposed onto subregions of the brain, and the ratio of striatal to background ROI values was used as a semi-quantitative outcome measure. All images were used in a human observer study, with four experienced investigators. The data from the observer and ROI studies were analysed using a receiver operating characteristic (ROC) analysis, where the area under the ROC curve (AUC) indicated the diagnostic accuracy. ROI analysis and human observers gave similar diagnostic performance (mean observer AUC = 0.89, best ROI AUC = 0.90). This suggested that the human observers are visually acquiring similar information from the images that are contained in the semi-quantitative striatal uptake.

Adult↗
PubMed2005

Optimal number of pinholes in multi-pinhole SPECT for mouse brain imaging--a simulation study.

This study simulates a multi-pinhole single-photon emission computed tomography (SPECT) system using the Monte Carlo method, and investigates different multi-pinhole designs for quantitative mouse brain imaging. Prior approaches investigating multi-pinhole SPECT were not often optimal, as the number and geometrical arrangement of pinholes were usually chosen empirically. The present study seeks to optimize the number of pinholes for a given pinhole arrangement, and also for the specific application of quantitative neuroreceptor binding in the mouse brain. An analytical Monte Carlo simulation based method was used to generate the projection data for various count levels. A three-dimensional ordered-subsets expectation-maximization algorithm was developed and used to reconstruct the images, incorporating a realistic pinhole model for resolution recovery and noise reduction. Although artefacts arising from overlapping projections could be a major problem in multi-pinhole reconstruction, the cold-rod phantom study showed minimal loss of spatial resolution in multi-pinhole systems, compared to a single-pinhole system with the same pinhole diameter. A quantitative study of neuroreceptor binding sites using a mouse brain phantom and low activity (37 MBq) showed that the multi-pinhole system outperformed the single-pinhole system by maintaining the mean and lowering the variance in the measured uptake ratio. Multi-pinhole collimation can be used to reduce the injected dose and thereby reduce the radiation exposure to the animal. Results also suggest that the nine-pinhole configuration shown in this paper is a good choice for mouse brain imaging.

Algorithms↗
PubMed2005

SPECT imaging of herpes simplex virus type1 thymidine kinase gene expression by [(123)I]FIAU(1).

RATIONALE AND OBJECTIVES: Introduction of suicide genes, such as herpes simplex virus type1 thymidine kinase (HSV1-tk), in tumor cells has provided a useful method for tumor gene therapy. Several L-nucleosides, such as Lamivudine (3TC) and Clevudine (L-FMAU), have been successfully tested as high-potency antiviral agents. To investigate the potential differences between D- and L-isomers of nucleosides, [(125/123)I]-2'-fluoro-2'-deoxy-1beta-D/L-arabino-furanosy-5-iodo-uracil (D/L-FIAU) have been synthesized and evaluated as potential SPECT agents for imaging HSV1-tk gene expression. MATERIALS AND METHODS: [(125/123)I]D- and L-FIAU were prepared by iododestannylation of the respective tin precursors with (125/123)I-sodium iodide. In vitro cell uptake studies were performed by incubation of [(125)I]D- and L-FIAU in RG2 cells expressing HSV1-tk (RG2TK+). In vivo studies including biodistribution and SPECT were performed in RG2TK+ and RG2TK- tumor-bearing nude mice using [(123)I]D- and L-FIAU. RESULTS: Cell uptake and biodistribution studies indicated that [(125/123)I]L-FIAU did not show any high accumulation (sensitivity) or uptake ratios (selectivity) in HSV1-TK-positive (RG2TK+) tumors as compared to control tumors. In contrast, [(125/123)I]D-FIAU displayed both sensitivity and selectivity to RG2TK+ tumors. The selective in vivo accumulation of [(123)I]D-FIAU increased with time and the tumor uptake ratios (RG2TK+/RG2TK-) for 2, 4, and 24 hours averaged 6.2, 22.7, and 58.8, respectively. High-resolution SPECT of four nude tumor-bearing mice demonstrated a very high uptake of [(123)I]D-FIAU in the RG2TK+ tumor, while no significant tracer accumulation was observed in the RG2TK- tumor and other organs. CONCLUSION: The data suggest that only the D-isomer of [(123)I]FIAU is useful for imaging HSV1-tk gene expression in mice by high-resolution SPECT imaging.

Animals↗
PubMed2005

Evidence of myocardial hibernation in the septic heart.

OBJECTIVE: Myocardial hibernation is an adaptive response to ischemia and hypoxia. Hibernating cardiomyocytes are reversibly hypocontractile and demonstrate characteristic metabolic and ultrastructural changes. These include a switch in primary substrate utilization from fatty acids to glucose, up-regulation of the myocardial specific glucose transporters (GLUT1 and GLUT4), and glycogen deposition within and between cardiomyocytes. We hypothesized that myocardial hibernation may underlie sepsis-associated myocardial depression. DESIGN: Prospective observational study aimed at identifying the characteristic changes of hibernation in the septic heart. SETTING: University hospital-based laboratory. SUBJECTS: Forty-three C57Bl6 male mice. INTERVENTIONS: Mice underwent cecal ligation and double puncture, sham operation, or no operation and were evaluated 48 hrs after the procedure. MEASUREMENTS AND MAIN RESULTS: Using novel, clinically relevant technology such as magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography imaging, we found septic mice to have diminished cardiac performance, increased myocardial glucose uptake, increased steady-state levels of myocardial GLUT4, and increased deposits of glycogen, recapitulating the changes during hibernation. Importantly, these changes occurred in the setting of preserved arterial oxygen tension and myocardial perfusion. CONCLUSIONS: Sepsis-associated cardiac dysfunction may reflect hibernation. Furthermore, such down-regulation of cellular function may underlie sepsis-induced dysfunction in other organ systems.

Animals↗
PubMed2005

In vivo detection of stem cells grafted in infarcted rat myocardium.

UNLABELLED: The evaluation of stem cell-mediated cardiomyoplasty by noninvasive in vivo imaging is critical for its clinical application. We hypothesized that dual-tracer small-animal SPECT would allow simultaneous imaging of (99m)Tc-sestamibi to assess myocardial perfusion and of (111)In-labeled stem cells to delineate stem cell engraftment. METHODS: Three to 4 million rat embryonic cardiomyoblasts (H9c2 cells) were labeled with 11.1-14.8 MBq (0.3-0.4 mCi) of (111)In-oxyquinoline and then injected into the border zones of infarcted myocardium of rats. (111)In images were acquired with a SPECT scanner 2, 24, 48, 72, and 96 h after the stem cells were injected into the infarcted myocardium. To visualize the perfusion deficit in the infarcted myocardium, we injected 74 MBq (2 mCi) of (99m)Tc-sestamibi (Cardiolite) intravenously 48 h after grafting. Dual-isotope pinhole SPECT was used to image (99m)Tc-sestamibi uptake simultaneously with (111)In to delineate retention of (111)In-labeled stem cells. The presence of labeled stem cells was confirmed by autoradiography and histology. RESULTS: SPECT of (99m)Tc-sestamibi was used to delineate perfusion deficits and infarcted myocardium. Bull's-eye plots indicated that the (111)In signal from the labeled stem cells overlapped the perfusion deficits identified from the (99m)Tc-sestamibi images. The (111)In signal associated with the radiolabeled stem cells could be detected with SPECT of the heart for 96 h after engraftment. CONCLUSION: This study demonstrated the feasibility of using dual-isotope pinhole SPECT for high-resolution detection of perfusion deficits with (99m)Tc-sestamibi and with (111)In-labeled stem cells grafted into the region of the infarct.

Animals↗
PubMed2004

2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine: an improved serotonin transporter imaging agent.

Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminomethyl)benzyl)-5-iodophenylamine (5) (K(i) for SERT = 0.37 and 48.6 nM, respectively). Both [(125)I]4 and [(125)I]5 displayed excellent brain uptakes in rats, and they showed a highest uptake in hypothalamus (between 60 and 240 min), a region populated with the highest density of SERT. The specific uptake of [(125)I]4 in the hypothalamus resulted in a target to nontarget ratio ([hypothalamus-cerebellum]/cerebellum) of 4.3 at 2 h. Autoradiography of rat brain sections (ex vivo at 2 h) of [(125)I]4 showed an excellent regional distribution pattern consistent with known SERT localization. These data suggest that [(123)I]4 may be useful for imaging SERT binding sites in the brain by single photon emission computed tomography (SPECT).

Aniline Compounds↗
PubMed2004

Differences in [99mTc]TRODAT-1 SPECT binding to dopamine transporters in patients with multiple system atrophy and Parkinson's disease.

PURPOSE: Multiple system atrophy (MSA), a disorder causing autonomic dysfunction, parkinsonism, and cerebellar dysfunction, is difficult to differentiate from other movement disorders, particularly early in the course of disease. This study evaluated whether [99mTc]TRODAT-1 binding to the dopamine transporter differentiates MSA from other movement disorders. METHODS: Single-photon emission computed tomographic brain scans were acquired in 25 MSA patients, 48 age-matched controls, and 130 PD patients, 3 h after the injection of 740 MBq (20 mCi) of [99mTc]TRODAT-1. Regions of interest (ROIs) were placed manually on subregions of both basal ganglia and distribution volume ratios (DVRs) were calculated. Regional DVRs were compared between study groups in MSA patients. Student's t tests were used to compare MSA patients with other study groups. Spearman correlations were used to compare DVRs with NP measures. RESULTS: Based upon various motor scores, MSA and PD patients had comparable motor impairment, and were significantly impaired compared with controls. Mean DVRs in the basal ganglia of MSA patients were significantly less than those of controls, but generally higher (p<0.05) than in PD patients. In particular, the MSA patients had significantly increased DVRs in the posterior putamen (mean 0.49+/-0.30) compared with PD patients (0.74+/-0.25). CONCLUSION: Movement disorder patients could be differentiated from controls, but MSA and PD patients could not be easily differentiated from each other. As a group, MSA patients had significantly higher mean [99mTc]TRODAT-1 binding, particularly in the posterior putamen, compared with PD patients and significantly lower binding compared with controls. This may reflect different pathophysiological processes of the two neurodegenerative diseases.

Adult↗
PubMed2004

Quantification in PET.

Quantification provides the link between the concentrations of radioactivity measured in tissue and the underlying physiologic processes occurring in the organ. It relates the rate at which radioactivity levels in the body change over time to quantitative parameters such as absolute rate glucose metabolism, regional blood flow, or concentrations of receptors or other binding sites. Absolute measurement of physiologic parameters generally requires accurate measurement of activity concentrations in arterial blood, which provides the input function to the kinetic model. Although absolute quantification can be a difficult process, simplifications of these invasive techniques, involving reference tissues or normalization approaches (eg, SUV), have been applied with some success. Any simplified model of tracer behavior must be validated against the full model to test for bias and systematic errors.

Algorithms↗
PubMed2003

In vivo quantitative noninvasive imaging of gene transfer by single-photon emission computerized tomography.

Systems aimed at detecting gene expression noninvasively in vivo are desirable for evaluating the outcome of gene transfer in clinical trials. Several approaches have been exploited using magnetic resonance imaging and spectroscopy ((31)P MRS), positron emission tomography (PET), single-photon emission tomography (SPECT), and detection of bioluminescent signals. An ideal system is based on transfer of a marker gene, the activity of which can be detected against a background from the target tissue without interfering with normal physiology or eliciting an immune response. The majority of approaches described to date use genes encoding a nonmammalian protein that can elicit immune responses or a transmembrane receptor as a marker gene whose ectopic expression may cause aberrant signaling in the target cell through binding to endogenous ligands. The dopamine transporter (DAT) is normally expressed at high levels, mainly in the dopaminergic neurons of the central nervous system. We previously synthesized a radioactive ligand, [(99m)Tc]TRODAT-1, that binds with high affinity to the dopamine transporter, allowing for SPECT imaging of the striatum in normal control subjects and individuals affected with Parkinson's disease. Here we describe a strategy to monitor gene transfer based on adeno-associated viral vector (AAV)-mediated transduction of DAT in murine muscle followed by [(99m)Tc]TRODAT-1 imaging by SPECT of cells expressing the transgene. We show that quantitative, noninvasive imaging of gene transfer is successfully achieved in vivo, using a single-photon computed tomography camera. This system employs a reporter gene encoding a mammalian protein that is absent in most tissues, has no enzymatic activity, and does not activate intracellular pathways. This should be useful to monitor gene transfer in the settings of gene therapy.

Animals↗
PubMed2003

The acute effect of methylphenidate on cerebral blood flow in boys with attention-deficit/hyperactivity disorder.

Methylphenidate (MPH) is the most commonly prescribed treatment for attention-deficit/hyperactivity disorder (ADHD). The therapeutic mechanisms of MPH are not, however, fully understood. We studied the effects of MPH on brain activity in male children and adolescents with ADHD, using the blood flow radiotracer technetium-99m ethyl cysteinate dimer ((99m)Tc-ECD) and single-photon emission tomography (SPET). The study was randomized, double blind, and placebo controlled (MPH group, n=19; placebo group, n=17), Radiotracer was administered during the performance of the Continuous Performance Test and before and after 4 days of MPH treatment. Statistical parametric mapping (SPM99) analysis showed a significant reduction in regional cerebral blood flow in the left parietal region in the MPH group compared with the placebo group (P<0.05, corrected for multiple comparisons). Our findings suggest that the posterior attentional system, which includes the parietal cortex, may have a role in the mediation of the therapeutic effects of MPH in ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Small animal imaging with high resolution single photon emission tomography.

Molecular imaging of small animals in vivo is vital in the study of mouse and rat models of human diseases, and will provide important clues to the pathogenesis, progression and treatment of many disorders. Functional imaging of small animals using ultra-high resolution single photon emission tomography (SPECT) should be a valuable tool in the molecular imaging armamentarium. SPECT has been used to study cerebral binding sites, to image the expression of reporter genes, and in applications in cardiology and oncology. In this review, we summarize the most recent developments in SPECT imaging of small animals, with particular reference to the types of systems available, their application, and some of the potential limitations.

Animals↗
PubMed2003

N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

UNLABELLED: There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. METHODS: This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. RESULTS: In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in rat brain (>96% of radioactivity was recovered as parent compound at 1 h after injection). However, it metabolized rapidly in the blood. Less than 7% of the radioactivity recovered from plasma was the parent compound, with the majority of radioactivity in the plasma not extractable by ethyl acetate. Blocking studies showed significant decreases in the uptake of 4-(18)F-ADAM in the brain regions (hypothalamus, hippocampus, and striatum) where SERT concentrations are high when rats were pretreated with (+)McN5652 (2 mg/kg 5 min before intravenous injection of 4-(18)F-ADAM). However, changes in the uptake of 4-(18)F-ADAM in these brain regions were less significant when rats were pretreated with either methylphenidate or nisoxetine. The baboon study showed that uptake of 4-(18)F-ADAM in the midbrain peaked at approximately 1 h after injection and then declined slowly. The ratios of the radioactivity in the midbrain to that in the cerebellum (where the concentration of SERT is low) at 2 and 3 h after injection were 3.2 and 4.2, respectively. CONCLUSION: 4-(18)F-ADAM is suitable as a PET radioligand for studying SERT in the living brain. Further characterization of this new radioligand in humans is warranted.

Animals↗
PubMed2002

Quantification of dopamine transporters in the mouse brain using ultra-high resolution single-photon emission tomography.

Functional imaging of small animals, such as mice and rats, using ultra-high resolution positron emission tomography (PET) and single-photon emission tomography (SPET), is becoming a valuable tool for studying animal models of human disease. While several studies have shown the utility of PET imaging in small animals, few have used SPET in real research applications. In this study we aimed to demonstrate the feasibility of using ultra-high resolution SPET in quantitative studies of dopamine transporters (DAT) in the mouse brain. Four healthy ICR male mice were injected with (mean+/-SD) 704+/-154 MBq [(99m)Tc]TRODAT-1, and scanned using an ultra-high resolution SPET system equipped with pinhole collimators (spatial resolution 0.83 mm at 3 cm radius of rotation). Each mouse had two studies, to provide an indication of test-retest reliability. Reference tissue kinetic modeling analysis of the time-activity data in the striatum and cerebellum was used to quantitate the availability of DAT. A simple equilibrium ratio of striatum to cerebellum provided another measure of DAT binding. The SPET imaging results were compared against ex vivo biodistribution data from the striatum and cerebellum. The mean distribution volume ratio (DVR) from the reference tissue kinetic model was 2.17+/-0.34, with a test-retest reliability of 2.63%+/-1.67%. The ratio technique gave similar results (DVR=2.03+/-0.38, test-retest reliability=6.64%+/-3.86%), and the ex vivo analysis gave DVR=2.32+/-0.20. Correlations between the kinetic model and the ratio technique ( R(2)=0.86, P<0.001) and the ex vivo data ( R(2)=0.92, P=0.04) were both excellent. This study demonstrated clearly that ultra-high resolution SPET of small animals is capable of accurate, repeatable, and quantitative measures of DAT binding, and should open up the possibility of further studies of cerebral binding sites in mice using pinhole SPET.

Animals↗