The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma.

The PET tracer O-(2-[18F]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.

The maximum uptake of (18)F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1alpha and GLUT-1 in non-small cell lung cancer.

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.

SPECT imaging in the diagnosis of pulmonary embolism: automated detection of match and mismatch defects by means of image-processing techniques.

UNLABELLED: SPECT of ventilation/perfusion (V/Q) lung scans not only improves the diagnostic accuracy of the method but also facilitates the application of advanced image-processing techniques. On the basis of such techniques, our study aimed at developing a procedure that automatically analyzes V/Q lung scans with regard to match and mismatch defects. METHODS: Fifty-three patients with suspected pulmonary embolism had lung scans using the SPECT technique as well as 16-slice multidetector-row spiral CT within an interval of 48 h. After iterative image reconstruction and computerized linear registration of the V/Q scans, the ventilation was normalized to the perfusion. For the automated detection of mismatch defects, the perfusion was subtracted from the ventilation, whereas for the detection of match defects, the perfusion was subtracted from the inverted ventilation. Two experienced referees assessed all images. The final diagnosis was made at a consensus meeting while taking into account all of the imaging modalities, laboratory tests, clinical data, and evaluation of a follow-up period. RESULTS: The sensitivity, specificity, and accuracy of the conventional visual assessment were 0.91, 0.97, and 0.94, respectively, compared with 0.95, 0.84, and 0.89, respectively, for the automated algorithm. Artifacts imitating mismatch defects in the pulmonary recesses accounted for the relatively low specificity of the automated analysis. Artifacts of that kind were found in 15 patients and led to a false-positive diagnosis in 5 patients. However, by combining the visual and the automated approach, all artifacts could be easily identified leading to a sensitivity, specificity, and accuracy of 0.95, 1.0, and 0.98, respectively. Additionally, in all 12 patients of the cohort with highly heterogeneous ventilation and perfusion, the automated analysis made correct diagnoses. CONCLUSION: Because of the 3-dimensional properties of the SPECT data, the analysis of lung scans can be automated and objectified. The algorithm produces images that are easy to read and well suited for demonstration. Because of artifacts in the pulmonary recesses introduced by the automated approach, its diagnostic accuracy does not reach the level of the conventional analysis yet. Could these artifacts be overcome, the efficiency of the automated algorithm would be at least equivalent to that of conventional image interpretation. At present, best results can be achieved by combining both approaches.

FDG--a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer.

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

[18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study.

BACKGROUND: Experimental and clinical evidence suggest that hypoxia in solid tumours reduces their sensitivity to conventional treatment modalities modulating response to ionizing radiation or chemotherapeutic agents. The aim of the present study was to show the feasibility of determining radiotherapeutically relevant hypoxia and early tumour response by ([18F] Fluoromisonidazole (FMISO) and [18F]-2-fluoro-2'-deoxyglucose (FDG) PET. METHODS: Eight patients with non-small-cell lung cancer underwent PET scans. Tumour tissue oxygenation was measured with FMISO PET, whereas tumour glucose metabolism was measured with FDG PET. All PET studies were carried out with an ECAT EXACT 922/47 scanner with an axial field of view of 16.2 cm. FMISO PET consisted of one static scan of the relevant region, performed 180 min after intravenous administration of the tracer. The acquisition and reconstruction parameters were as follows: 30 min emission scanning and 4 min transmission scanning with 68-Ge/68-Ga rod sources. The patients were treated with chemotherapy, consisting of 2 cycles of gemcitabine (1200 mg/m2) and vinorelbine (30 mg/m2) followed by concurrent radio- (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine (300-500 mg/m2) every two weeks. FMISO PET and FDG PET were performed in all patients 3 days before and 14 days after finishing chemotherapy. RESULTS: FMISO PET allowed for the qualitative and quantitative definition of hypoxic sub-areas which may correspond to a localization of local recurrences. In addition, changes in FMISO and FDG PET measure the early response to therapy, and in this way, may predict freedom from disease, as well as overall survival. CONCLUSION: These preliminary results warrant validation in larger trials. If confirmed, several novel treatment strategies may be considered, including the early use of PET to evaluate the effectiveness of the selected therapy.

Selective mediastinal node irradiation based on FDG-PET scan data in patients with non-small-cell lung cancer: a prospective clinical study.

PURPOSE: To evaluate the patterns of recurrence when selective mediastinal node irradiation based on FDG-PET scan data is used in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A prospective Phase I/II study was undertaken on 44 patients with NSCLC without detectable distant metastases on CT and FDG-PET scan, delivering either 61.2 Gy in 34 fractions over 23 days or 64.8 Gy in 36 fractions over 24 days (1.8 Gy b.i.d. with 8-h interval). Only the primary tumor and the positive mediastinal areas on the pretreatment FDG-PET scan were irradiated. Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-field failure. RESULTS: The CT and FDG-PET stage distribution was as follows: Stage I: 8 patients (18%) and 13 patients (29%); Stage II: 6 patients (14%) and 10 patients (23%); Stage IIIA: 15 patients (34%) and 7 patients (16%); Stage IIIB: 15 patients (34%) and 14 patients (32%), respectively. After a median follow-up time of 16 months (95% confidence interval [CI], 11-21 months) postradiotherapy, 11 patients (25%) developed a local recurrence. Only 1 patient (crude rate, 2.3%; upper bound of 95% CI, 10.3%), with a Stage II tumor on both CT and PET, developed an isolated nodal failure. The median actuarial overall survival was 21 months (95% CI, 14-28 months), and the median actuarial progression-free survival was 18 months (95% CI, 12-24 months). CONCLUSIONS: Selective mediastinal node irradiation based on FDG-PET scan data in patients with NSCLC results in low isolated nodal failure rates. In the Phase I component of this trial, radiation dose escalation up to 64.8 Gy in 36 fractions over 24 days is feasible.

Tomographic imaging in the diagnosis of pulmonary embolism: a comparison between V/Q lung scintigraphy in SPECT technique and multislice spiral CT.

UNLABELLED: Although ventilation/perfusion (V/Q) lung scintigraphy is a well-accepted and frequently performed procedure in the diagnosis of pulmonary embolism, there is growing controversy about its relevance, particularly due to the increasing competition between scintigraphy and CT. Even though comparative studies between both modalities have already been performed, their results were highly inconsistent. Remarkably, in most of those studies, conventional planar perfusion scans were compared with tomographic images acquired using state-of-the-art CT scanners-a study design that cannot give impartial results. Hence, the aim of our study was a balanced comparison between V/Q lung scintigraphy and CT angiography using advanced imaging techniques for both modalities. METHODS: A total of 83 patients with suspected pulmonary embolism were examined using V/Q lung scintigraphy in SPECT technique as well as 4-slice spiral CT. Ventilation scans were done using an ultrafine aerosol. Additionally, planar images in 8 views were extracted from the V/Q SPECT datasets. Two experienced referees assessed each of the 3 modalities. The final diagnosis was made at a consensus meeting while taking into account all of the imaging modalities, laboratory tests, clinical data, and evaluation of a follow-up period. RESULTS: In the course of the consensus conference, pulmonary embolism was diagnosed in 37 of the 83 patients (44.6%). Compared with planar scintigraphy, SPECT raised the number of detectable defects at the segmental level by 12.8% (+11 defects; P = 0.401) and at the subsegmental level by 82.6% (+57 defects; P < 0.01). The sensitivity/specificity/accuracy of planar V/Q scintigraphy and V/Q SPECT was 0.76/0.85/0.81 and 0.97/0.91/0.94, respectively, compared with 0.86/0.98/0.93 for multislice CT. CONCLUSION: SPECT and ultrafine aerosols are technical advancements that can substantially improve lung scintigraphy. Using advanced imaging techniques, V/Q scintigraphy and multislice spiral CT both yield an excellent and, in all aspects, comparable diagnostic accuracy, with CT leading in specificity while SPECT shows a superior sensitivity. Even though planar lung scintigraphy yields satisfactory results for a nontomographic modality, it does not compare with tomographic imaging.

Comparison of regional myocardial blood flow and perfusion in dilated cardiomyopathy and left bundle branch block: role of wall thickening.

UNLABELLED: Heterogeneous perfusion in left bundle branch block (LBBB) has been demonstrated by (99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT. Locally different contraction is also associated with LBBB. Quantitative analysis of myocardial SPECT is influenced by partial-volume effects depending on systolic wall thickening. Therefore, partial-volume effects may mimic perfusion heterogeneity in LBBB. METHODS: Fifteen patients with nonischemic dilated cardiomyopathy and LBBB underwent resting (15)O-water PET, (99m)Tc-MIBI SPECT, and gated (18)F-FDG PET for analysis of wall thickening. Myocardial blood flow corrected for rate-pressure product (corrMBF), (99m)Tc-MIBI uptake, and wall thickening were determined in 4 left ventricular wall areas. In 14 patients, M-mode echocardiographic recordings were available for comparison. RESULTS: Homogeneous distribution was found for corrMBF (1.09 +/- 0.41 to 1.19 +/- 0.31 mL x g(-1) x min(-1)). (99m)Tc-MIBI uptake and wall thickening were heterogeneous (P < 0.0001), with the lowest values septal ((99m)Tc-MIBI, 65% +/- 10%; wall thickening, 16% +/- 14%) and the highest lateral ((99m)Tc-MIBI, 84% +/- 5%; wall thickening, 55% +/- 17%). Similar relationships in systolic wall thickening were observed by M-mode echocardiography (anteroseptal, 20% +/- 11%; posterolateral, 37% +/- 18%; P < 0.001). CONCLUSION: Heterogeneity of (99m)Tc-MIBI uptake in LBBB corresponds to differences in wall thickening and does not reflect distribution of corrMBF. Supplementary analysis of wall thickening is recommended when assessing (99m)Tc-MIBI SPECT in LBBB.

Effects of cardiac resynchronization therapy on myocardial blood flow measured by oxygen-15 water positron emission tomography in idiopathic-dilated cardiomyopathy and left bundle branch block.

Regional and global myocardial blood flow and coronary vascular resistance were determined in patients with idiopathic-dilated cardiomyopathy and left bundle branch block before and during cardiac resynchronization therapy (CRT) using oxygen-15 water positron emission tomography. The investigated parameters did not exhibit regional heterogeneity and were not influenced by CRT. This implies that the beneficial effects of CRT do not require additional oxygen demand or regional reallocation of oxidative metabolism.

Comparison of SSS and SRS calculated from normal databases provided by QPS and 4D-MSPECT manufacturers and from identical institutional normals.

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 > or =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 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.

Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells.

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.

Gemcitabine concurrent with thoracic radiotherapy after induction chemotherapy with gemcitabine/vinorelbine in locally advanced non-small cell lung cancer: a phase I study.

PURPOSE: To determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m(2)) and vinorelbine (30 mg/m(2)) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [(18)F] fluorodeoxyglucose positron emission tomography-(FDG-PET-)based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m(2). The dose of gemcitabine was increased by 100 mg/m(2) until the MTD was realized. Three patients were enrolled for each dose level. RESULTS: Dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m(2), due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. CONCLUSION: After induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m(2) every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy.

Side-by-side reading of PET and CT scans in oncology: which patients might profit from integrated PET/CT?

PURPOSE: Most early publications on integrated positron emission tomography/computed tomography (PET/CT) devices have reported the new scanner generation to be superior to conventional PET. However, few of these studies have analysed the situation where, in addition to PET, a current CT scan is available for side-by-side viewing. This fact is important, because combined PET/CT or a software-based fusion of the two modalities may improve diagnosis only in cases where side-by-side reading of PET and CT data does not lead to a definitive diagnosis. The aim of this study was to analyse which patients will profit from integrated PET/CT in terms of lesion characterization. METHODS: A total of 328 consecutively admitted patients referred for PET in whom a current CT scan was available were included in the study. The localization of all pathological PET lesions, as well as possible infiltration of adjacent anatomical structures, was assessed. RESULTS: Of 467 pathological lesions, 94.0% were correctly assessed with respect to localization and infiltration by either conventional PET alone (51.6%) or combined reading of PET and the already existing CT scans (42.4%). Hence, in only 6.0% of all lesions, affecting 6.7% of all patients, could evaluation have profited from integrated PET/CT. CONCLUSION: We conclude that side-by-side viewing of PET and CT scans is essential, as in 42.4% of all cases, combined viewing was important for a correct diagnosis in our series. In up to 6.7% of patients, integrated PET/CT might have given additional information, so that in nearly 50% of patients some form of combined viewing of PET and CT data is needed for accurate lesion characterization.