U. Buell

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

PurposeMost 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.MethodsA 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.ResultsOf 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.ConclusionWe 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.

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

PurposeCell-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 111In-oxine has been used in preclinical trials. This study aimed to validate 111In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells.MethodsMurine haematopoietic progenitor cells (106, FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose) 111In-oxine and compared with unlabelled controls. Cellular retention of 111In, 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.ResultsLabelling efficiency was 75±14%. Cellular retention of incorporated 111In 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.ConclusionRadiolabelling of haematopoietic progenitor cells with 111In-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.

Influence of diabetes mellitus on regional cerebral glucose metabolism and regional cerebral blood flow.

Previous studies have shown both increased and decreased regional cerebral glucose metabolism-blood flow (rMRGlu-rCBF) values in diabetes. We sought to elucidate the influence of diabetes on rMRGlu-rCBF in 57 patients with pure cerebral microangiopathy. Sixteen of 57 patients had diabetes requiring therapy (11 NIDDM, 5 IDDM). Using a special head-holder for exact repositioning, rMRGlu (PET) and rCBF (SPET) were imaged and measured in slices, followed by MRI. White matter and cortex were defined within regions of interest taken topographically from MRI (overlay). Diabetic and non-diabetic microangiopathy patients were compared to 19 age-matched controls. The diabetic patients showed significantly lower rMRGlu-rCBF values in all regions than controls, whereas non-diabetic patients did not. There were no significant NIDDM-IDDM differences. rMRGlu-rCBF did not depend on venous blood glucose levels at the time of the PET examination. However, analysis of variance with the factors diabetes, atrophy and morphological severity of microangiopathy showed that lowered rMRGlu-rCBF in the diabetic group was due to concomitant atrophy only (P<0.005), while neither diabetes nor microangiopathy had any influence on rMRGlu-rCBF (all P>0.2). These results were confirmed by multivariate factor analysis. It can thus be concluded that a supposed decrease in rMRGlu-rCBF in diabetes mellitus is in fact only an artefact produced by the concomitant atrophy. All previous studies failed to correct for atrophy, and a critical reappraisal is required.

Comparison of visual and ROI-based brain tumour grading using 18F-FDG PET: ROC analyses

Several studies have suggested that the use of simple visual interpretation criteria for the investigation of brain tumours by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) might be similarly or even more accurate than quantitative or semi-quantitative approaches. We investigated this hypothesis by comparing the accuracy of FDG-PET brain tumour grading using a proposed six-step visual grading scale (VGS; applied by three independent observers unaware of the clinical history and the results of histopathology) and three different region of interest (ROI) ratios (maximal tumour uptake compared with contralateral tissue [Tu/Tis], grey matter [Tu/GM] and white matter [Tu/WM]). The patient population comprised 47 patients suffering from 17 benign (7 gliomas of grade II, 10 non-gliomatous tumours) and 30 malignant (23 gliomas of grade III–IV, 7 non-gliomatous tumours) tumours. The VGS results were highly correlated with the different ROI ratios (R=0.91 for Tu/GM, R=0.82 for Tu/WM, and R=0.79 for Tu/Tis), and high inter-observer agreement was achieved (κ=0.63, 0.76 and 0.81 for the three observers). The mean ROI ratios and VGS readings of gliomatous and non-gliomatous lesions were not significantly different. For all measures, high-grade lesions showed significantly higher FDG uptake than low-grade lesions (P<0.005 to P<0.0001, depending on the measure used). Nominal logistic regressions and receiver operating characteristic (ROC) analyses were used to calculate cut-off values to differentiate low- from high-grade lesions. The predicted (by ROC) diagnostic sensitivity/specificity of the different tests (cut-off ratios shown in parentheses) were: Tu/GM: 0.87/0.85 (0.7), Tu/WM: 0.93/0.80 (1.3), Tu/Tis: 0.80/0.80 (0.8) and VGS: 0.84/0.95 (uptake < GM, but >> WM). The VGS yielded the highest Az (±SE) value (i.e. area under the ROC curve as a measure of predicted accuracy), 0.97±0.03, which showed a strong tendency towards being significantly greater than the Az of Tu/Tis (0.88±0.06; P=0.06). Tu/GM (0.92±0.04) and Tu/WM (0.91±0.05) reached intermediate Az values (not significantly different from any other value). We conclude that the VGS represents a measure at least as accurate as the Tu/GM and Tu/WM ratios. The Tu/Tis ratio is less valid owing to the high dependence on the location of the lesion. Depending on the investigators experience and the structure of the lesions, the easily used VGS might be the most favourable grading criterion.

Dual-head gamma camera 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography in oncological patients: effects of non-uniform attenuation correction on lesion detection

Abstract. The purpose of this study was to evaluate a dual head coincidence gamma camera (DH-PET) equipped with single-photon transmission for 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) imaging in oncological patients. Forty-five patients with known or suspected malignancies, scheduled for a positron emission tomography (PET) scan, were first studied with a dedicated ring PET and subsequently with DH-PET. All patients underwent measured attenuation correction using germanium-68 rod sources for ring PET and caesium-137 sources for DH-PET. Ring PET emission scan was started 64±17 min after intravenous administration of 235±42 MBq FDG. DH-PET emission followed 160±32 min after i.v. FDG. Attenuation-corrected and non-attenuation-corrected images were reconstructed for ring PET and DH-PET. The image sets were evaluated independently by three observers blinded to clinical data and to results of conventional imaging. Attenuation-corrected ring PET as the standard of reference depicted 118 lesions, non-attenuation-corrected ring PET 113 (96%) lesions, and attenuation-corrected DH-PET and non-attenuation-corrected DH-PET, 101 (86%) and 84 (71%) lesions, respectively (P<0.05). The lesion detection rate of attenuation-corrected and non-attenuation-corrected DH-PET was almost similar for lesions >20 mm, whereas attenuation correction increased the detection rate from 60% to 80% for lesions ≤20 mm (P<0.01). A patient-based analysis revealed concordant results relative to attenuation-corrected ring PET for non-attenuation-corrected ring PET, attenuation-corrected DH-PET and non-attenuation-corrected DH-PET in 42 (93%), 36 (80%) and 31 (69%) patients, respectively. Differences might have influenced patient management in two (4%), six (13%) and ten (22%) patients, respectively. In conclusion, measured attenuation correction markedly improves the lesion detection capability of DH-PET. With measured attenuation correction the diagnostic performance of DH-PET is closer to that of dedicated ring PET.

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.

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/m2) and vinorelbine (30 mg/m2) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [18F] 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/m2. The dose of gemcitabine was increased by 100 mg/m2 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/m2, 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/m2 every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy.Ziel:Festlegung der maximal tolerablen Dosis (MTD) von Gemcitabin, verabreicht im 14-tägigen Intervall parallel zur perkutanen Radiotherapie, appliziert während einer dosisdichten Therapie, bestehend aus sequentieller und simultaner Radio-/Chemotherapie, bei lokal fortgeschrittenem, inoperablem nichtkleinzelligen Bronchialkarzinom (NSCLC).Patienten und Methodik:Zehn Patienten mit histologisch gesichertem NSCLC wurden gemäß Studienprotokoll mit kombinierter Radio-/Chemotherapie behandelt. Dieses beinhaltete zwei Zyklen Induktionschemotherapie mit Gemcitabin (1 200 mg/m2) und Vinorelbin (30 mg/m2) an Tag 1, 8 sowie 22, 29, gefolgt von einer simultanen Radio-/Chemotherapie mit Gemcitabin im 2-wöchigen Abstand, an den Tagen 43, 57 und 71. Die initiale Gemcitabin-Dosis betrug 300 mg/m2. Die Dosis wurde in 100-mg/m2-Schritten bis zum Erreichen der MTD gesteigert. In jeder Dosisstufe wurden drei Patienten aufgenommen. Parallel dazu wurde eine Radiotherapie mit [18F]-Fluorodeoxyglucose-Positronenemissionstomographie-(FDG-PET-)basierter Zielvolumendefinition (2,0 Gy/d; Gesamtdosis 66,0 Gy) durchgeführt.Ergebnisse:Die dosislimitierende Toxizität (DLT) wurde bei der Gabe von 500 mg/m2 erreicht. In dieser Dosisstufe zeigte sich bei allen Patienten eine Grad-2-Ösophagitis (unmittelbar am Übergang in eine Grad-3-Ösophagitis). Des Weiteren zeigten sich bei der ersten Nachsorge ca. 6 Wochen nach Abschluss der Behandlung weiterhin entzündliche Veränderungen der Speiseröhre. Aufgrund der zu erwartenden Komplikationen wie einer Ösophagitis Grad 3–4, Dysphagie und Odynophagie wurde die MTD bei dieser Dosisstufe definiert, obwohl keine DLT Grad 3 erreicht wurde.Schlussfolgerung:Nach Induktionschemotherapie lagen die MTD und Frequenz von Gemcitabin bei 500 mg/m2 im 14-tägigen Intervall parallel zur Radiotherapie.

99Tcm-methoxyisobutylisonitrile stress/rest SPECT in patients with constant complete left bundle branch block.

Numerous studies have revealed frequent false positive septal findings of 201Tl stress imaging in patients with left bundle branch block (LBBB) even with angiographically excluded significant coronary artery disease (CAD). To scrutinize this phenomenon for stress/rest 99Tcm-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) was used to review 22 patients with constant LBBB. The findings were reversible septal defect in one patient, partially reversible septal defect in one patient and irreversible septal defects in eight patients. In four patients 99Tcm-MIBI scans were entirely normal. Thus, 12/22 (55%) patients revealed normal septal 99Tcm-MIBI uptake. Both patients with a stress-induced septal defect revealed a significant left anterior descending artery stenosis on coronary angiography. These preliminary results suggest, that 99Tcm-MIBI might be more specific and accurate than 201Tl in the evaluation of CAD in patients with LBBB because of apparently rare or absent false positive septal findings.

Imaging of β-oxidation by static PET with 14(R,S)-[18F]-fluoro-6-thiaheptadecanoic acid (FTHA) in patients with advanced coronary heart disease : A comparison with 18FDG-PET and 99Tcm-MIBI SPET

14(R,S)-[18F]-fluoro-6-thiaheptadecanoic acid (FTHA) has been proposed as a PET tracer of the beta-oxidation pathway. The aim of this study was to investigate the diagnostic value of FTHA using static PET imaging in patients with ischaemically reduced left ventricular function. Twenty-one patients with angiographically proven advanced coronary heart disease were examined. All patients underwent SPET with 400 MBq [99Tcm]-2-methoxy-isobutyl-isonitrile (MIBI) for perfusion assessment and PET with 250 MBq FTHA under fasting conditions and with 150 MBq 2-[18F]-fluoro-2-deoxyglucose (FDG) following an oral glucose load. The uptake of FTHA and FDG was analysed quantitatively in 33 regions. Regional uptake was normalized to the region with highest MIBI uptake and expressed as a percentage. FTHA uptake paralleled MIBI uptake (r = 0.80) but not FDG uptake (r = 0.57). Mean FTHA uptake (38.1 +/- 16.3%) in 190 regions with severely reduced perfusion (MIBI uptake < 50%, mean uptake 36.8 +/- 9.4%) was significantly lower compared to FDG uptake (54.6 +/- 25.0%). FTHA uptake was preserved (> or = 70%) in 8 of 52 (13%) regions only with severely reduced perfusion but preserved glucose metabolism (FDG uptake > or = 70%). The similarity between FTHA and MIBI uptake suggests that static PET imaging with FTHA is of limited value when distinguishing between ischaemic or hibernating myocardium and scar. The underestimation of viability may be caused both by the dependence of uptake on flow and the suppression of beta-oxidation in regional chronic ischaemia under fasting conditions.

18FDG-PET in 733 consecutive patients with or without side-by-side CT evaluation Analysis of 921 lesions

UNLABELLED Side-by-side analysis of CT and conventional (18)FDG-PET in oncological imaging is well established. AIM of this study was to find out which patients or diagnostic groups may benefit the most from the newly introduced integrated PET/CT scanners. PATIENTS, METHODS 407 consecutively admitted oncological patients with accompanying CT (groups A-D) and 326 patients without CT (groups E-G) were examined by conventional ring PET. Two nuclear medicine physicians and two radiologists assessed each patients PET and CT scans for pathological lesions with regard to localisation and infiltration of adjacent anatomical structures. Patients without pathological PET findings were assigned to groups A (with CT) or E (without CT). If the localisation and/or extent of a pathological PET focus could only be assessed by taking into account the CT scan, the patient was assigned to group C (with CT) or G (without CT). If PET alone was sufficient for both questions the patient was assigned to groups B (with CT) or F (without CT). If neither method allowed for a precise lesion characterisation, the patient was assigned to group D. RESULTS 38.6% (A, E) of all patients were PET-negative. PET alone sufficed in 20.6% (B, F). Side-by-side reading of PET and CT was needed for 43.5% (C) of patients referred to PET with a current CT. Side-by-side reading of CT and PET did not suffice for 7.3% (D) of patients in that cohort. A total of 28.2% (G) of the cases without CT would have profited from it. The most frequent oncological diagnoses in group D (PET and conventional CT not sufficient) were bronchial carcinoma with abdominal lesions, while in group G (without CT but CT required) head/neck cancer with thoracic lesions was predominant. CONCLUSIONS Side-by-side reading of PET and already existing conventional CT failed to yield conclusive data with regard to lesion characterisation in only 7.4% of patients so that PET/CT might have been helpful in these cases. 28.2% of the patients without current CT would have profited from an initial PET/CT examination. On the other hand, 59.2% of all patients (negative PET or PET alone sufficing) did not require a CT for lesion characterisation.