The PET tracer O-(2-[(18)F]Fluoroethyl)-l-tyrosine (FET) has been shown to be valuable for different roles in the management of brain tumours. The aim of this study was to evaluate several quantitative measures of dynamic FET PET imaging in patients with resected glioblastoma. We evaluated dynamic FET PET in nine patients with histologically confirmed glioblastoma. Following FET PET, all subjects had radiation and chemotherapy. Tumour ROIs were defined by a threshold-based region-growing algorithm. We compared several standard measures of tumour uptake and uptake kinetics: SUV, SUV/background, distribution volume ratio (DVR), weighted frame differences and compartment model parameters. These measures were correlated with disease-free and overall survival, and analysed for statistical significance. We found that several measures allowed robust quantification. SUV and distribution volume did not correlate with clinical outcome. Measures that are based on a background region (SUV/BG, Logan-DVR) highly correlated with disease-free survival (r =-0.95, p < 0.0001), but not overall survival. Some advanced measures also showed a prognostic value but no improvement over the simpler methods. We conclude that FET PET probably has a prognostic value in patients with resected glioblastoma. The ratio of SUV to background may provide a simple and valuable predictive measure of the clinical outcome. Further studies are needed to confirm these explorative results.

PURPOSE: There is proven evidence for the importance of myocardial perfusion-single-photon emission computed tomography (SPECT) with computerised determination of summed stress and rest scores (SSS/SRS) for the diagnosis of coronary artery disease (CAD). SSS and SRS can thereby be calculated semi-quantitatively using a 20-segment model by comparing tracer-uptake with values from normal databases (NDB). Four severity-degrees for SSS and SRS are normally used:<4, 4-8, 9-13, and >/=14. Manufacturers' NDBs (M-NDBs) often do not fit the institutional (I) settings. Therefore, this study compared SSS and SRS obtained with the algorithms Quantitative Perfusion SPECT (QPS) and 4D-MSPECT using M-NDB and I-NDB. METHODS: I-NDBs were obtained using QPS and 4D-MSPECT from exercise stress data (450 MBq (99m)Tc-tetrofosmin, triple-head-camera, 30 s/view, 20 views/head) from 36 men with a low post-stress test CAD probability and visually normal SPECT findings. Patient group was 60 men showing the entire CAD-spectrum referred for routine perfusion-SPECT. Stress/rest results of automatic quantification of the 60 patients were compared to M-NDB and I-NDB. After reclassifying SSS/SRS into the four severity degrees, kappa (kappa) values were calculated to objectify agreement. RESULTS: Mean values (vs M-NDB) were 9.4 +/- 10.3 (SSS) and 5.8 +/- 9.7 (SRS) for QPS and 8.2 +/- 8.7 (SSS) and 6.2 +/- 7.8 (SRS) for 4D-MSPECT. Thirty seven of sixty SSS classifications (kappa = 0.462) and 40/60 SRS classifications (kappa = 0.457) agreed. Compared to I-NDB, mean values were 10.2 +/- 11.6 (SSS) and 6.5 +/- 10.4 (SRS) for QPS and 9.2 +/- 9.3 (SSS) and 7.2 +/- 8.6 (SRS) for 4D-MSPECT. Forty four of sixty patients agreed in SSS and SRS (kappa = 0.621 resp. 0.58). CONCLUSION: Considerable differences between SSS/SRS obtained with QPS and 4D-MSPECT were found when using M-NDB. Even using identical patients and identical I-NDB, the algorithms still gave substantial different results.

AIM: The standardized uptake value (SUV) of (18)FDG-PET is an important parameter for therapy monitoring and prognosis of malignant lesions. SUV determination requires delineating the respective volume of interest against surrounding tissue. The present study proposes an automatic image segmentation algorithm for lesion volume and FDG uptake quantitation. METHODS: A region growing-based algorithm was developed, which goes through the following steps: 1. Definition of a starting point by the user. 2. Automatic determination of maximum uptake within the lesion. 3. Calculating a threshold value as percentage of maximum. 4. Automatic 3D lesion segmentation. 5. Quantitation of lesion volume and SUV. The procedure was developed using CTI CAPP and ECAT 7.2 software. Validation was done by phatom studies (Jaszczak phantom, various "lesion" sizes and contrasts) and on studies of NSCLC patients, who underwent clinical CT and FDG-PET scanning. RESULTS: Phantom studies demonstrated a mean error of 3.5% for volume quantification using a threshold of 41% for contrast ratios >/=5 : 1 and sphere volumes >5 ml. Comparison between CT- and PET-based volumetry showed a high correlation of both methods (r = 0.98) for lesions with homogeneous FDG uptake. Radioactivity concentrations were underestimated by on average -41%. Employing an empirical threshold of 50% for SUV determination, the underestimation decreased to on average -34%. CONCLUSIONS: The algorithm facilitates an easy and reproducible SUV quantification and volume assessment of PET lesions in clinical practice. It was validated using NSCLC patient data and should also be applicable to other tumour entities.

The purpose of this study was to investigate the relation between the standardised uptake value (SUV) on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan and hypoxia related markers (HIF-1alpha and CAIX), a proliferation-related marker (Ki-67) and glucose transporters (GLUT-1 and GLUT-3) in non-small cell lung cancer (NSCLC). One hundred and two patients, scheduled for complete resection, received a PET scan in Leuven or Maastricht/Aachen. The maximal SUV (SUV(max)) was correlated with survival and immunohistochemical staining patterns. The actuarial survival was worse for patients showing a high SUV(max), the best discriminative value being 8.0 (Leuven, p=0.032) and 11.0 (Maastricht, p=0.007). Tumours with a high SUV(max) expressed in a higher proportion HIF-1alpha (63.1% versus 37.9%, p=0.024) and GLUT-1 (82.9% versus 62.5%, p=0.025), than tumours with a low SUV(max). No significant difference was found in the expression of CAIX, Ki-67 and GLUT-3. This study supports preclinical data that hypoxia is associated with a higher uptake of FDG.

AIM: Using 8-frames/cardiac cycle with gated SPECT underestimates end-diastolic volumes (EDV) and ejection fractions (LVEF), and overestimates end-systolic volumes (ESV). However, using 16-frames/cardiac cycle significantly decreases the signal-to-noise-ratio. We analyzed 16-frames and rebinned 8-frame gated SPECT data using common 4D-MSPECT and QGS algorithms. PATIENTS, METHODS: 120 patients were examined using gated SPECT on a Siemens Multispect 3 (triple-head gamma camera) 60 minutes after intravenous administration at rest of about 450 MBq (two-day protocol) or about 750 MBq (one-day protocol)(99m)Tc-tetrofosmin. Reoriented short axis slices (16-frames) were summed framewise (1+2,3+4, etc.) yielding 8-frame data sets. EDV, ESV and LVEF were calculated for both data sets using 4D-MSPECT and QGS. RESULTS: QGS succeeded with 119, 4D-MSPECT with 117 patients. For the remaining 116 patients, higher EDV (+0.8ml/+3.8 ml) and LVEF (+1.5%/+2.6%; absolute) and lower ESV (-1.7ml/-0.9 ml)(4D-MSPECT/QGS) were found for 16-frame runs. Bland-Altman limits were smaller for QGS than 4D-MSPECT [EDV 32/12 ml, ESV 21/10 ml, LVEF 17/7%(4D-MSPECT/QGS)]. CONCLUSION: Both algorithms showed the expected effects. Contour finding using QGS failed with only one data set, whereas contour finding using 4D-MSPECT failed with three data sets. Since the effects observed between the 8- and the 16-frame studies are relatively small and quite predictable, 8-frame studies can be employed in clinical routine with hardly any loss at all, plus contour finding appears less susceptible to error.

PURPOSE: The segmentation algorithm ESM based on an elastic surface model was validated for the assessment of left ventricular volumes and ejection fraction from ECG-gated myocardial perfusion SPECT. Additionally, it was compared with the commercially available quantification packages 4D-MSPECT and QGS. Cardiac MRI was used as the reference method. METHODS: SPECT and MRI were performed on 70 consecutive patients with suspected or proven coronary artery disease. End-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were derived from SPECT studies by using the segmentation algorithms ESM, 4D-MSPECT and QGS and from cardiac MRI. RESULTS: ESM-derived values for EDV and ESV correlated well with those from cardiac MRI (correlation coeffients R = 0.90 and R = 0.95, respectively), as did the measurements for LVEF (R = 0.86). Both EDV and ESV were slightly overestimated for larger ventricles but not for smaller ventricles; LVEF was slightly overestimated irrespective of ventricle size. The above correlation coefficients are comparable to those for the 4D-MSPECT and QGS segmentation algorithms. However, results obtained with the three segmentation algorithms are not interchangeable. CONCLUSION: The ESM algorithm can be used to assess EDV, ESV and LVEF from gated perfusion SPECT images. Overall, the performance was similar to that of 4D-MSPECT and QGS when compared with cardiac MRI. Results obtained with the three tested segmentation methods are not interchangeable, so that the same algorithm should be used for follow-up studies and control subjects.

PURPOSE: Cell-based therapy by transplantation of progenitor cells has emerged as a promising development for organ repair, but non-invasive imaging approaches are required to monitor the fate of transplanted cells. Radioactive labelling with (111)In-oxine has been used in preclinical trials. This study aimed to validate (111)In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells. METHODS: Murine haematopoietic progenitor cells (10(6), FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose)(111)In-oxine and compared with unlabelled controls. Cellular retention of (111)In, viability and proliferation were determined up to 48 h after labelling. Labelled cells were injected into the cavity of the left or right cardiac ventricle in mice. Scintigraphic images were acquired 24 h later. Organ samples were harvested to determine the tissue-specific activity. RESULTS: Labelling efficiency was 75 +/- 14%. Cellular retention of incorporated (111)In after 48 h was 18 +/- 4%. Percentage viability after 48 h was 90 +/- 1%(control), 58 +/- 7%(low dose) and 48 +/- 8%(high dose)(p<0.0001). Numbers of viable cells after 48 h (normalised to 0 h) were 249 +/- 51%(control), 42 +/- 8%(low dose) and 32 +/- 5%(high dose)(p<0.0001). Cells accumulated in the spleen (86.6 +/- 27.0% ID/g), bone marrow (59.1 +/- 16.1% ID/g) and liver (30.3 +/- 9.5% ID/g) after left ventricular injection, whereas most of the cells were detected in the lungs (42.4 +/- 21.8% ID/g) after right ventricular injection. CONCLUSION: Radiolabelling of haematopoietic progenitor cells with (111)In-oxine is feasible, with high labelling efficiency but restricted stability. The integrity of labelled cells is significantly affected, with substantially reduced viability and proliferation and limited migration after systemic transfusion.

OBJECTIVE: In the European Stroke Prevention Study (ESPS 2), oral administration of a fixed combination of 200 mg extended-release dipyridamole and 25 mg aspirin (twice daily) after ischemic stroke or transient ischemic attack, significantly reduced the risk of stroke compared to placebo as well as compared to aspirin or dipyridamole alone. However, the i.v. application of dipyridamole over 4 - 6 min is known to increase myocardial blood flow up to 6-fold, and thereby potentially provoke ischemic wall motion abnormalities in patients with coronary artery disease. We therefore assessed the cardiac side effects of the dipyridamole/aspirin combination on absolute myocardial blood flow (MBF) and coronary vascular resistance (CVR). METHODS: MBF and CVR were measured using 150-water positron emission tomography in 24 patients after stroke or transient ischemic attack, before and 6.7 +/- 1.9 days after starting the dipyridamole/aspirin combination (Aggrenox) therapy. RESULTS: Resting MBF increased by 39%(max. 112%), from 0.92 +/- 0.13 (ml x g(-1) x min(-1)) at baseline to 1.28 +/- 0.27 (ml x g(-1) x min(-1)) under ongoing dipyridamole/aspirin combination therapy (p < 0.0005). CVR consecutively decreased from 105.3 +/- 16.9 to 74.1 +/- 16.5 (mmHg x ml(-1) x g x min)(p < 0.0005). The relative increase in MBF correlated negatively with the body surface area. No correlation was found between relative MBF increase and duration of dipyridamole/aspirin combination therapy (range 4 - 10 days). CONCLUSIONS: Orally administered dipyridamole/aspirin combination therapy in secondary stroke prevention increases MBF and decreases CVR significantly. These cardiac side effects of the dipyridamole/aspirin combination should be taken into account in stroke patients with proven or suspected coronary artery disease, particularly in combination with a small body surface area.

PURPOSE: Experimental data suggest that the accumulation of [(18)F]fluorodeoxyglucose (FDG) in malignant tumours is related to regional hypoxia. The aim of this study was to evaluate the clinical potential of FDG positron emission tomography (PET) to assess tumour hypoxia in comparison with [(18)F]fluoromisonidazole (FMISO) PET and pO(2)-polarography. METHODS: Twenty-four patients with head and neck malignancies underwent FDG PET, FMISO PET, and pO(2)-polarography within 1 week. Parameters of pO(2)-polarography were the relative frequency of pO(2) readings </=2.5 mmHg,</=5 mmHg and </=10 mmHg, respectively, as well as the mean and median pO(2). RESULTS: We observed a moderate correlation of the maximum standardised uptake value (SUV) of FDG with the tumour to blood ratio of FMISO at 2 h (R=0.53, p<0.05). However, SUV of FDG was similar in hypoxic and normoxic tumours as defined by pO(2)-polarography (6.9+/-3.2 vs 6.2+/-3.0, NS), and the FDG uptake was not correlated with the results of pO(2)-polarography. The retention of FMISO was significantly higher in hypoxic tumours than in normoxic tumours (tumour to muscle ratio at 2 h: 1.8+/-0.4 vs 1.4+/-0.1, p<0.05), and the FMISO tumour to muscle ratio showed a strong correlation with the frequency of pO(2) readings </=5 mmHg (R=0.80, p<0.001). CONCLUSION: These results support the hypothesis that tumour hypoxia has an effect on glucose metabolism. However, other factors affecting FDG uptake may be more predominant in chronic hypoxia, and thus FDG PET cannot reliably differentiate hypoxic from normoxic tumours.