Introduction.
Currently, there is a lack of data on the role of combined positron emission tomography–computed tomography (PET–CT) in the staging of early invasive primary breast cancer. We therefore ...evaluated the role of 18F‐fluorodeoxyglucose (18F‐FDG)‐PET–CT in this patient population.
Methods.
We prospectively recruited 70 consecutive patients (69 women, one man; mean age, 61.9 ± 8.1 years) with early primary breast cancer for staging with 18F‐FDG‐PET–CT. All PET–CT images were interpreted by two readers (independently of each other). A third reader adjudicated any discrepancies. All readers had ≥5 years of specific experience. Ethics board approval and informed consent were obtained.
Results.
The mean clinical follow‐up was 22.7 ± 12.6 months. The primary tumor was identified with PET–CT in 64 of 70 patients. Of the unidentified lesions, surgical pathology revealed two intraductal carcinomas, one invasive tubular carcinoma, and three invasive lobular carcinomas. Undiagnosed multifocal breast disease was shown in seven of 70 patients. PET–CT identified avid axillary lymph nodes in 19 of 70 patients, compared with 24 of 70 confirmed during surgery. There were four patients who were axillary node positive on PET but had no axillary disease at surgery.
Five patients were reported with avid metastases. Two of those patients were treated for metastatic disease (nodal, lung, and liver in one and bone metastases in the other) following further imaging and clinical assessment. In the other three patients, lesions (lung, n = 1; pleural, n = 1; paratrachael node, n = 1) were subsequently diagnosed as benign lesions.
Conclusion.
Integrated 18F‐FDG‐PET–CT may have a role in staging patients presenting with early breast cancer.
The role of 18F‐fluorodeoxyglucose positron emission tomography–computed tomography in the staging of early invasive primary breast cancer was evaluated.
Antipsychotic drugs modulate N-methyl-D-aspartate (NMDA) receptor function in animals. The novel single photon emission tomography (SPET) radiotracer
123ICNS-1261 binds to the PCP/MK-801 ...intrachannel site of the NMDA receptor, allowing the noninvasive estimation of NMDA receptor activity in living humans. We used
123ICNS-1261 to determine whether binding to the NMDA receptor intrachannel PCP/MK-801 site is affected by schizophrenia or by treatment with typical antipsychotics and clozapine in vivo.
Three groups of schizophrenia patients were recruited—drug free (n = 5), typical antipsychotic treated (n = 7), and clozapine treated (n = 9)—as well as a control group of healthy normal volunteers (n = 13). All underwent
123ICNS-1261 SPET scanning. Total volume of distribution of
123ICNS-1261 was determined within predefined user-independent regions of interest after alignment of all images to a common template.
There was no apparent difference in total volume of distribution of
123ICNS-1261 in drug-free patients relative to healthy control subjects. A nonsignificant reduction in total volume of distribution was observed in typical antipsychotic treated patients. A significant decline in total volume of distribution of
123ICNS-1261 was observed in all examined brain regions in the clozapine-treated patient group relative to healthy control subjects (p < .005).
Clozapine treatment resulted in a global reduction in
123ICNS-1261 binding to the NMDA receptor intrachannel PCP/MK-801 site in vivo. This supports an effect of the drug on glutamatergic systems that could be exploited for future antipsychotic drug discovery.
INTRODUCTIONA three-dimensional model-based resolution recovery (RR) reconstruction algorithm that compensates for collimator–detector response, resulting in an improvement in reconstructed spatial ...resolution and signal-to-noise ratio of single-photon emission computed tomography (SPECT) images, was tested. The software is said to retain image quality even with reduced acquisition time. Clinically, any improvement in patient throughput without loss of quality is to be welcomed. Furthermore, future restrictions in radiotracer supplies may add value to this type of data analysis.
AIMThe aims of this study were to assess improvement in image quality using the software and to evaluate the potential of performing reduced time acquisitions for bone and parathyroid SPECT applications.
MATERIALS AND METHODSData acquisition was performed using the local standard SPECT/CT protocols for Tc-hydroxymethylene diphosphonate bone and Tc-methoxyisobutylisonitrile parathyroid SPECT imaging. The principal modification applied was the acquisition of an eight-frame gated data set acquired using an ECG simulator with a fixed signal as the trigger. This had the effect of partitioning the data such that the effect of reduced time acquisitions could be assessed without conferring additional scanning time on the patient. The set of summed data sets was then independently reconstructed using the RR software to permit a blinded assessment of the effect of acquired counts upon reconstructed image quality as adjudged by three experienced observers. Data sets reconstructed with the RR software were compared with the local standard processing protocols; filtered back-projection and ordered-subset expectation-maximization.
RESULTSThirty SPECT studies were assessed (20 bone and 10 parathyroid). The images reconstructed with the RR algorithm showed improved image quality for both full-time and half-time acquisitions over local current processing protocols (P<0.05).
CONCLUSIONThe RR algorithm improved image quality compared with local processing protocols and has been introduced into routine clinical use. SPECT acquisitions are now acquired at half of the time previously required. The method of binning the data can be applied to any other camera system to evaluate the reduction in acquisition time for similar processes. The potential for dose reduction is also inherent with this approach.
OBJECTIVE: Atypical antipsychotic drug treatment is clinically effective with a low risk of extrapyramidal symptoms. Explanations for the mechanism underlying this beneficial therapeutic profile of ...atypical over typical antipsychotic agents include 1) simultaneous antagonism of dopamine D2 and serotonin 5-HT2A receptors or 2) selective action at limbic cortical dopamine D2-like receptors with modest striatal D2 receptor occupancy. Amisulpride is an atypical antipsychotic drug with selective affinity for D2 D3 dopamine receptors and provides a useful pharmacological model for examining these hypotheses. The authors' goal was to evaluate whether treatment with amisulpride results in "limbic selective" D2 D3 receptor blockade in vivo. METHOD: Five hours of dynamic single photon emission tomography data were acquired after injection of 123Iepidepride (approximately 150 MBq). Kinetic modeling was performed by using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a healthy volunteer comparison group (N=6). RESULTS: Eight amisulpride-treated patients (mean dose=406 mg day) showed moderate levels of D2 D3 receptor occupancy in the striatum (56%), and significantly higher levels were seen in the thalamus (78%) and temporal cortex (82%). CONCLUSIONS: Treatment with amisulpride results in a similar pattern of limbic cortical over striatal D2 D3 receptor blockade to that of other atypical antipsychotic drugs. This finding suggests that modest striatal D2 receptor occupancy and preferential occupancy of limbic cortical dopamine D2 D3 receptors may be sufficient to explain the therapeutic efficacy and low extrapyramidal symptom profile of atypical antipsychotic drugs, without the need for 5-HT2A receptor antagonism.
We prospectively investigated the potential of positron emission tomography (PET) using the somatostatin receptor (SSTR) analogue 68Ga-DOTATATE and 2-deoxy-218Ffluoro-D-glucose (18F-FDG) in diffuse ...parenchymal lung disease (DPLD). Twenty-six patients (mean age 68.9 ± 11.0 years) with DPLD were recruited for 68Ga-DOTATATE and 18F-FDG combined PET/high-resolution computed tomography (HRCT) studies. Ten patients had idiopathic pulmonary fibrosis (IPF), 12 patients had nonspecific interstitial pneumonia (NSIP), and 4 patients had other forms of DPLD. Using PET, the pulmonary tracer uptake (maximum standardized uptake value SUVmax) was calculated. The distribution of PET tracer was compared to the distribution of lung parenchymal changes on HRCT. All patients demonstrated increased pulmonary PET signal with 68Ga-DOTATATE and 18F-FDG. The distribution of parenchymal uptake was similar, with both tracers corresponding to the distribution of HRCT changes. The mean SUVmax was 2.2 ± 0.7 for 68Ga-DOTATATE and 2.8 ± 1.0 (t-test, p = .018) for 18F-FDG. The mean 68Ga-DOTATATE SUVmax in IPF patients was 2.5 ± 0.9, whereas it was 2.0 ± 0.7 (p = .235) in NSIP patients. The correlation between 68Ga-DOTATATE SUVmax and gas transfer (transfer factor of the lung for carbon monoxide TLCO) was r = .34 (p = .127) and r = .49 (p = .028) between 18F-FDG SUVmax and TLCO. We provide noninvasive in vivo evidence in humans showing that SSTRs may be detected in the lungs of patients with DPLD in a similar distribution to sites of increased uptake of 18F-FDG on PET.
Serotonergic brain regions play a crucial role in the modulation of emotion, and serotonergic dysfunction may contribute to several neurological disorders. 123IADAM is a novel SPECT tracer which ...binds with high affinity to serotonin transporters (SERT). The objective of this study was to compare different methods for the quantification of tracer binding and to develop a simplified single-scan protocol for this tracer, as well as to investigate its potential for characterisation of the transporter occupancy versus plasma concentration curve of a selective serotonin re-uptake inhibitor (SSRI).
Dynamic SPECT scans were performed on 16 healthy volunteers after administration of approximately 150 MBq 123IADAM. Data were acquired from the time of injection until approximately 5.5 h after injection in 30- or 45-min sessions. Each subject was scanned twice: with and without pre-treatment with the SSRI citalopram in various dosage regimens. The plasma concentration of citalopram (C(p)) was determined from venous samples. Images were reconstructed by filtered back-projection with scatter and attenuation correction. Tracer binding was quantified for midbrain, striatum and thalamus using cerebellum as a reference region. Quantification was done by kinetic modelling, graphical analysis and multi-linear regression, as well as by the ratio method, with binding potential (BP2) as the outcome measure. The SERT occupancy by citalopram was determined relative to the baseline scan for each subject, and the occupancy versus C(p) curve was fitted with the E(max) model.
The highest binding of 123IADAM was in midbrain (mean baseline BP2+/-SD=1.31+/-0.29), with lower binding in thalamus (0.79+/-0.16) and striatum (0.66+/-0.13). There was good agreement between BP2 values obtained by different quantification methods. Using the ratio method, the best agreement with kinetic modelling was obtained with data from the time interval 200,260 min after injection. The fitting of the midbrain occupancy curve yielded a maximum occupancy of 84% and a plasma concentration required to reach 50% of the maximum of 2.5 ng/ml, with a goodness-of-fit variability of 13% (SD).
Binding of 123IADAM to SERT in midbrain can be quantified with a single scan starting 200 min after injection. However, the variability of estimated occupancy values may be too high for critical assessment of occupancy of SERT by SSRI.
Purpose
Despite modern CT systems and expert evaluators, the diagnostic performance of coronary CT angiography is limited by overestimation of vessel stenosis which reduces the positive predictive ...value (PPV) of the test. The aim of this study was to evaluate the performance of combined cardiac PET/64-detector CT angiography.
Methods
Included in this retrospective study were 33 consecutive patients (5 women, 28 men; mean age 61.6 years, range 47–87 years, mean BMI 27.3±5.2 kg/m
2
) with clinically suspected flow-limiting coronary artery disease who underwent combined cardiac PET/64-detector CT angiography and invasive angiography. Combined PET/CT images were reported by an experienced dual-accredited radiologist/nuclear physician. An experienced cardiac CT radiologist re-read the CT images without PET. Stenotic disease was defined as >50% vessel narrowing. Invasive coronary angiography was used as a reference standard. Local ethics committee approval and patient consent were obtained.
Results
CT angiography (without PET data) was concordant with invasive angiography in 31/33 patients and at a patient level, the sensitivity in detecting significant coronary artery lesions was 100%, the specificity was 82%, the PPV was 92% and the negative predictive value (NPV) was 100%. Using combined PET/CT angiography the findings were concordant with invasive angiography in 32/33 patients and at a patient level, the sensitivity was 96%, the specificity was 100%, the PPV was 100% and the NPV was 91%.
Conclusion
The use of integrated cardiac PET/64-detector CT angiography is feasible and appears to improve some aspects of the diagnostic performance of 64-detector coronary artery angiography in detecting coronary artery disease.
To assess the effect of polyethylene glycol 400 (PEG 400), a pharmaceutical excipient frequently employed to enhance the solubility and bioavailability of poorly water-soluble drugs, on the ...gastrointestinal transit of liquid and pellet preparations in human subjects using gamma scintigraphy.
Ten, healthy male volunteers each received, on separate occasions, a liquid preparation consisting of 150 ml orange juice (control) or 150 ml orange juice containing 10 g PEG 400 (test). Non-disintegrating pellets of size 1.4-1.7 mm. encapsulated within a hard gelatin capsule, were simultaneously administered on both occasions to act as a marker for solid dosage form transit. The liquid and pellet preparations were radiolabelled with 111In and 99mTc respectively thus enabling their positions within the gastrointestinal tract to be followed using a gamma camera.
Rapid liquid emptying from the stomach was observed, with no significant difference noted in the gastric residence times of the two preparations. Caecum arrival times for the liquid preparations were significantly different by virtue of their differential rates of transit through the small intestine. The mean small intestinal liquid transit time for the control preparation was 236 min whereas the corresponding value for the PEG 400-containing test preparation was 153 min. This 35% reduction in transit time was attributed to the presence of PEG 400. Pellet transit was largely unaffected by the presence of PEG 400.
These findings clearly demonstrate that PEG 400 has a marked accelerating effect on small intestinal liquid transit, which in turn has implications for the formulation of poorly water-soluble drugs with PEG 400.
Purpose
To assess the feasibility and first experience of combined
18
F-FDG-PET)/dynamic contrast-enhanced (DCE) CT in evaluating breast cancer.
Methods
Nine consecutive female patients (mean age ...64.2 years, range 52–74 years) with primary breast carcinoma were prospectively recruited for combined
18
F-FDG PET/DCE-CT. Dynamic CT data were used to calculate a range of parameters of tumour vascularity, and tumour
18
F-FDG uptake (standardized uptake value, SUVmax) was used as a metabolic indicator.
Results
One tumour did not enhance and was excluded. The mean tumour SUVmax was 7.7 (range 2.4–26.1). The mean values for tumour perfusion, perfusion normalized to cardiac output, standard perfusion value (SPV) and permeability were 41 ml/min per 100 g (19–59 ml/min per 100 g), 0.56%/100 g (0.33–1.09%/100 g), 3.6 (2.5–5.9) and 0.15/min (0.09–0.30/min), respectively. Linear regression analysis showed a positive correlation between tumour SUV and tumour perfusion normalized to cardiac output (
r
=0.55,
p
=0.045) and a marginal correlation between tumour SUV and tumour SPV (
r
=0.19,
p
=0.065). There were no significant correlations between tumour SUV and tumour perfusion (
r
=0.29,
p
=0.401) or permeability (
r
=0.03,
p
=0.682).
Conclusion
The first data from combined
18
F-FDG-PET/DCE-CT in breast cancer are reported. The technique was successful in eight of nine patients. Breast tumour metabolic and vascular parameters were consistent with previous data from
15
O-H
2
O-PET.
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