Glucose utilisation and cell proliferation in colorectal cancer.
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Cell Division↗
Biomedical subjects
D Visvikis
Publications and source records attributed to D Visvikis.
The impact of FDG-PET on the management algorithm for recurrent colorectal cancer.
Positron emission tomography (PET) has been successfully used to image colorectal cancer (CRC). This study evaluated the accuracy of 2-[(18)F]-fluoro-2-deoxy- D-glucose (FDG) PET for the detection and staging of recurrent CRC and the consequent impact on clinical management. Forty-two patients previously treated for CRC were investigated for suspected recurrence and, if recurrence was confirmed, the extent of disease was evaluated. All patients underwent whole-body FDG-PET and computed tomography (CT) scan and results were compared to assess sensitivity, specificity and diagnostic accuracy for each modality. We then assessed the FDG-PET directed alteration in clinical management from that planned on the basis of spiral CT results. FDG-PET was more sensitive (93%) than CT (73%) for detection of recurrence (specificity 58% and 75%, respectively). FDG-PET yielded a correct diagnosis in 35 (83%) out of 42 patients, while CT did so in 31 patients (74%). FDG-PET was more accurate than CT for staging local recurrence (sensitivity 100%, specificity 86% with FDG-PET vs 75% and 100%, respectively, with CT) and CRC liver metastases (sensitivity 100% vs 45%; specificity 100% for both). Overall, PET upstaged 8 out of 30 patients (27%) and altered patient management in 16 (38%) cases. This study confirms that FDG-PET is more sensitive than CT for the detection and staging of recurrent CRC. The results also indicate that FDG-PET is an accurate means of selecting appropriate patients for operative treatment. When applied to routine clinical practice, patient management is altered.
Aged↗
In vivo 5-HT2A receptor blockade by quetiapine: an R91150 single photon emission tomography study.
BACKGROUND: Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms. METHOD: 5-HT2A binding was estimated using 123I-5-I-R91150 and single photon emission tomography (SPET) in six schizophrenic subjects treated with quetiapine at a mean (+/-SD) daily dose of 350+/-123 mg for at least 5 weeks and a matched sample of six healthy volunteers. Clinical and side-effect ratings were performed at baseline and at the time of SPET scanning. The reference region approach was used to define a 5-HT2A binding index in the frontal and temporal cortex. RESULTS: Quetiapine treatment resulted in a significant decline in 5-HT2A receptor availability in the frontal cortex (mean 0.98+/-0.09) relative to healthy volunteers (mean 1.33+/-0.16). All patients showed improvements in clinical symptom or side-effect ratings. The mean frontal cortex:cerebellum ratio after quetiapine treatment was significantly negatively correlated with reduction in the Abnormal Involuntary Rating scale and Simpson-Angus scores (P<0.05 Bonferroni corrected), but not with the reduction in the scores from the scale for the assessment of positive symptoms, the scale for the assessment of negative symptoms, the Montgomery-Asberg depression rating scale or patient age. CONCLUSION: Quetiapine treatment results in significant in vivo blockade of cortical 5-HT2A, similar to other atypical antipsychotic drugs. This effect may contribute to its placebo level extrapyramidal side-effect profile.
Adult↗
Functional imaging of malignant paragangliomas and carcinoid tumours.
Complete staging is mandatory for the management and therapy of neuroendocrine tumours. Various radiotracers are available but the best imaging strategy has yet to be defined. In this study we retrospectively compared 123I-MIBG, 111In-[D-Phe1]-DTPA-octreotide and 18F-FDG (PET) imaging in 15 patients with metastatic neuroendocrine tumours (11 carcinoid tumours, 4 paragangliomas). Planar images were acquired 1, 4, 24 and 48 h following the injection of 111In-[D-Phe1]-DTPA-octreotide and 123I-MIBG. Whole-body PET scans were performed 45 min after injection of 18F-FDG. 111In-[D-Phe1]-DTPA-octreotide was positive in 11/15 patients and identified 44 lesions, 18F-FDG PET was positive in 11/15 patients and identified 107 lesions and 123I-MIBG was positive in 8/15 patients and identified 67 lesions. No single scintigraphic technique identified all metastatic sites. In one patient all studies were negative. 18F-FDG PET identified more abnormal sites than the other two modalities. Combination of all three imaging modalities with X-ray CT helps to provide a more comprehensive map of the disease.
3-Iodobenzylguanidine↗
Positron emission tomography and colorectal cancer.
BACKGROUND: The oncological applications of positron emission tomography (PET) have gained widespread acceptance. This rapidly evolving technology has been applied successfully to colorectal cancer, but has not yet become part of routine clinical practice. This review considers (1) the biological basis for the use of PET in colorectal cancer, (2) the technical aspects of PET relevant to the referring clinician and (3) the application of PET to the management of primary and recurrent disease. METHODS: A Medline database search was performed for the period 1980-2000. Experience was also drawn from the first 40 patients with colorectal cancer investigated at this institution. RESULTS AND CONCLUSION: PET has a proven role, and is cost effective in the management of recurrent cancer and the monitoring of therapy. However, further evaluation is still required to justify its routine use for other indications in colorectal cancer. Development of new positron-labelled radio- pharmaceuticals, in parallel with advances in detector technology and innovative models for tracer production and distribution, means that the availability of PET and its applications in the management of colorectal cancer will expand over the coming years.
Colorectal Neoplasms↗
Influence of OSEM and segmented attenuation correction in the calculation of standardised uptake values for [18F]FDG PET.
Standardised Uptake Values (SUVs) are widely used in positron emission tomography (PET) as a semi-quantitative index of fluorine-18 labelled fluorodeoxyglucose uptake. The objective of this study was to investigate any bias introduced in the calculation of SUVs as a result of employing ordered subsets-expectation maximisation (OSEM) image reconstruction and segmented attenuation correction (SAC). Variable emission and transmission time durations were investigated. Both a phantom and a clinical evaluation of the bias were carried out. The software implemented in the GE Advance PET scanner was used. Phantom studies simulating tumour imaging conditions were performed. Since a variable count rate may influence the results obtained using OSEM, similar acquisitions were performed at total count rates of 34 kcps and 12 kcps. Clinical data consisted of 100 patient studies. Emission datasets of 5 and 15 min duration were combined with 15-, 3-, 2- and 1-min transmission datasets for the reconstruction of both phantom and patient studies. Two SUVs were estimated using the average (SUVavg) and the maximum (SUVmax) count density from regions of interest placed well inside structures of interest. The percentage bias of these SUVs compared with the values obtained using a reference image was calculated. The reference image was considered to be the one produced by filtered back-projection (FBP) image reconstruction with measured attenuation correction using the 15-min emission and transmission datasets for each phantom and patient study. A bias of 5%-20% was found for the SUVavg and SUVmax in the case of FBP with SAC using variable transmission times. In the case of OSEM with SAC, the bias increased to 10%-30%. An overall increase of 5%-10% was observed with the use of SUVmax. The 5-min emission dataset led to an increase in the bias of 25%-100%, with the larger increase recorded for the SUVmax. The results suggest that OSEM and SAC with 3 and 2 min transmission may be reliably used to reduce the overall data acquisition time without compromising the accuracy of SUVs.
Fluorodeoxyglucose F18↗
Modeling dynamic PET-SPECT studies in the wavelet domain.
This work develops a theoretical framework and corresponding algorithms for the modeling of dynamic PET-SPECT studies both in time and space. The problem of estimating the spatial dimension is solved by applying the wavelet transform to each scan of the dynamic sequence and then performing the kinetic modeling and statistical analysis in the wavelet domain. On reconstruction through the inverse wavelet transform, one obtains parametric images that are consistent estimates of the spatial patterns of the kinetic parameter of interest. The theoretical setup allows the use of linear techniques currently used in PET-SPECT for kinetic analysis. The method is applied to artificial and real data sets. The application to dynamic PET-SPECT studies was performed both for validation purposes, when the spatial patterns are known, and for illustration of the advantages offered by the technique in case of tracers with an unknown pattern of distribution.
Benzamides↗
In vivo serotonin 5-HT(2A) receptor occupancy and quetiapine.
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Adult↗
Striatal and extra-striatal D(2)/D(3) dopamine receptor occupancy by quetiapine in vivo. [(123)I]-epidepride single photon emission tomography(SPET) study.
BACKGROUND: Selective action at limbic cortical dopamine D(2)-like receptors could mediate atypical antipsychotic efficacy with few extrapyramidal side-effects. AIMS: To test the hypothesis that quetiapine has 'limbic selective' D(2)/D(3) receptor occupancy in vivo. METHOD: The high-affinity D(2)/D(3) ligand [(123)I]-epidepride and single photon emission tomography were used to estimate D(2)/D(3) specific binding and an index of relative percentage D(2)/D(3) occupancy in striatal and temporal cortical regions for quetiapine-treated patients (n=6). Quetiapine-, and previously studied typical-antipsychotic- and clozapine-treated patients were compared. RESULTS: Mean (s.d.) relative percentage D(2)/D(3) receptor occupancy by quetiapine was 32.0% (14.6) in striatum and 60.1% (17.2) in temporal cortex (mean daily dose 450 mg: range 300-700 mg/day). Quetiapine treatment resulted in limbic selective D(2)/D(3) blockade similar to clozapine and significantly higher than typical antipsychotics. CONCLUSIONS: Preliminary data suggest that limbic selective D(2)/D(3) receptor blockade is important for atypical drug action.
Adult↗
Multiresolution analysis of emission tomography images in the wavelet domain.
This article develops a theoretical framework for the use of the wavelet transform in the estimation of emission tomography images. The solution of the problem of estimation addresses the equivalent problems of optimal filtering, maximum compression, and statistical testing. In particular, new theory and algorithms are presented that allow current wavelet methodology to deal with the two main characteristics of nuclear medicine images: low signal-to-noise ratios and correlated noise. The technique is applied to synthetic images, phantom studies, and clinical images. Results show the ability of wavelets to model images and to estimate the signal generated by cameras of different resolutions in a wide variety of noise conditions. Moreover, the same methodology can be used for the multiscale analysis of statistical maps. The relationship of the wavelet approach to current hypothesis-testing methods is shown with an example and discussed. The wavelet transform is shown to be a valuable tool for the numerical treatment of images in nuclear medicine. It is envisaged that the methods described here may be a starting point for further developments in image reconstruction and image processing.
Algorithms↗
In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs. [123I]epidepride single photon emission tomography (SPET) study.
BACKGROUND: The dopamine hypothesis proposes that antipsychotic drugs act primarily through limbic cortical D2/D2-like dopamine receptor blockade. AIM: To evaluate this hypothesis with the D2/D3-selective SPET probe [123I]-epidepride. METHOD: [123I]-epidepride SPET scans were performed on 12 patients with schizophrenia treated with antipsychotics and II age-matched healthy controls. [123I]-epidepride 'specific binding' to D2/D3 dopamine receptors was estimated, and relative percentage D2/D3 receptor occupancy by typical antipsychotic drugs determined. RESULTS: Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equivalents. Mean percentage D2/D3 receptor occupancy was 81.6 (8.1) and 73.2 (13.9) in the temporal cortex and striatum respectively. CONCLUSIONS: Typical antipsychotic drug treatment is associated with substantial temporal cortical D2/D3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia.
Adult↗
Intercomparison of four reconstruction techniques for positron volume imaging with rotating planar detectors.
Four reconstruction techniques for positron volume imaging have been evaluated for scanners based on rotating planar detectors using measured and simulated data. The four techniques compared are backproject then filter (BPF), the 3D reprojection (3D RP) method for 3D filtered backprojection (FBP), Fourier rebinning (FORE) in conjunction with 2D FBP (FORE + 2D FBP) and 3D ordered subsets expectation maximization (3D OSEM). The comparison was based on image resolution and on the trade-off between contrast and noise. In general FORE + 2D FBP offered a better contrast-noise trade-off than 3D RP, whilst 3D RP offered a better trade-off than BPF. Unlike 3D RP, FORE + 2D FBP did not suffer any contrast degradation effect at the edges of the axial field of view, but was unable to take as much advantage from high-accuracy data as the other methods. 3D OSEM gave the best contrast at the expense of greater image noise. BPF, which demonstrated generally inferior contrast-noise behaviour due to use of only a subset of the data, gave more consistent spatial resolution over the field of view than the projection-data based methods, and was best at taking full advantage of high-accuracy data.
Computer Simulation↗