Patrick Reinartz

pO(2) Polarography versus positron emission tomography ([(18)F] fluoromisonidazole, [(18)F]-2-fluoro-2'-deoxyglucose). An appraisal of radiotherapeutically relevant hypoxia.

Background and Purpose:The aim of the present study was to validate ([18F] fluoromisonidazole (FMISO) and [18F]-2-fluoro-2’-deoxyglucose (FDG) positron emission tomography (PET) for determination of radiotherapeutically relevant hypoxia by the gold standard for measuring tissue oxygenation in human tumors, the computerized polarographic needle electrode system (pO2 histography).Patients and Methods:Up to now, a total of 16 patients with a metastatic neck lymph node from a primary squamous carcinoma of the head and neck underwent pO2 and PET measurements. Tumor tissue pO2 was measured with polarographic needle electrodes using a pO2 histograph (Eppendorf®). Under CT control, the needle electrode was placed in the tumor without general or local anesthesia. To assess the biological and clinical relevance of oxygenation measurement, the relative frequency of pO2 readings, with values ≤ 2.5, ≤ 5.0, and ≤ 10.0 mmHg, as well as mean and median pO2 were recorded.All PET studies were carried out using 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 120 min after intravenous administration. The acquisition and reconstruction parameters were as follows: 15-min emission scanning and 4-min transmission scanning with 68Ge rod sources. FDG PET of the lymph node metastasis was performed 68 ± 11 min after intravenous administration, applying the whole-body tool with 8-min emission scanning and 4-min transmission scanning per bed position.Results:In order to detect possible relations between the different relevant polarographically measured parameters of tumor hypoxia and FMISO PET data-based oxygenation values, the Pearson correlation coefficient was calculated. Average (r > 0.5) to high correlation (r > 0.7) was found between tumor-to-muscle ratio of FMISO after 2 h and parameters of hypoxic fraction (pO2 readings with values ≤ 2.5, ≤ 5.0, and ≤ 10.0 mmHg as well as mean and median). No correlations could be shown between FDG PET parameters and polarographically determined tumor oxygenation status.Conclusion:Summarizing the FMISO uptake represents a global value for macroscopic tumor parts. As a noninvasive measurement this method seems highly feasible to evaluate the state of oxygenation in subjacent tumors.Hintergrund und Ziel:Ziel dieser Untersuchung war die Validierung von [18F]-Fluormisonidazol-(FMISO-) und [18F]-Fluordeoxyglucose-( FDG-)Positronenemissionstomographie (PET) zur Erfassung der strahlentherapeutisch relevanten Hypoxie durch das computergestützte polarographische Nadelelektrodensystem (pO2-Histographie), das den Goldstandard zur Festlegung der Gewebeoxygenierung in menschlichen Tumoren darstellt.Patienten und Methodik:Bis jetzt wurden bei insgesamt 16 Patienten mit metastatisch befallenen Halslymphknoten eines Plattenepithelkarzinoms der Kopf-Hals-Region pO2- und PET-Messungen durchgeführt. Der pO2 des Tumorgewebes wurde mit Hilfe polarographischer Feinnadelelektroden eines pO2-Histographen (Eppendorf®) gemessen. Die Nadelelektrode wurde CT-gesteuert ohne Lokalanästhesie positioniert. Als Grad für die biologische und klinische Relevanz wurden die relative Häufigkeit der pO2-Messwerte ≤ 2,5, ≤ 5,0 und ≤ 10,0 mmHg sowie der Mittelwert und der Median dokumentiert.Die PET-Untersuchungen wurden an einem Vollring-Tomographen (ECAT EXACT 922/47®; Siemens/CTI) durchgeführt. Die FMISO-PET erfolgte als statische Aufnahme der relevanten Region 120 min p.i. Folgende Akquisitions- und Rekonstruktionsparameter wurden verwendet: 15-minütige Emissionsmessung und 4-minütige Transmissionsmessung mit Hilfe von 68Ge-Stabquellen. Die FDG-PET der metastatisch befallenen Halslymphknoten wurde 68 ± 11 min p.i. unter Verwendung eines Ganzkörperprotokolls mit einer Emissionsmessung von 8 min und einer Transmissionsmessung von 4 min pro Bettposition durchgeführt.Ergebnisse:Um mögliche Korrelationen zwischen den verschiedenen relevanten, polarographisch gemessenen Parametern der Tumorhypoxie und den mittels FMISO-PET gewonnenen Messdaten zu detektieren, wurde der Pearson-Korrelationskoeffizient berechnet. Es zeigte sich eine mittlere (r > 0,5) bis hohe Korrelation (r > 0,7) zwischen dem Tumor/Muskel-Quotienten der FMISO-Aufnahme 2 h p. i. und den verschiedenen Hypoxieparametern (pO2-Messwerte ≤ 2,5, ≤ 5,0, ≤ 10,0 mmHg sowie Mittelwert und Median der pO2-Messwerte). Keine Korrelation konnte zwischen den FDG-PET-Parametern und dem polarographisch bestimmten Tumoroxygenierungsstatus aufgezeigt werden.Schlussfolgerung:Die mit PET gemessene FMISO-Aufnahme gibt einen globalisierten Messwert für makroskopische Anteile des Tumors wieder. Aufgrund des nichtinvasiven Charakters scheint diese Methode besonders geeignet, den Oxygenierungsstatus bei tiefer liegenden Tumoren zu erfassen.

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.

Benign versus malignant osseous lesions in the lumbar vertebrae : differentiation by means of bone SPET

Abstract.Bone scanning is a well-accepted and frequently performed diagnostic procedure with a high sensitivity, especially when single-photon emission tomography (SPET) acquisitions are added. However, the differentiation of benign from malignant osseous lesions often poses difficulty. The purpose of this study was to find out whether the particular localisation of an intraosseous lesion in a lumbar vertebra is an indicator of its aetiology. Bone scintigraphy including planar whole-body scans as well as SPET imaging of the lumbar spine was performed in 109 patients. The diagnoses of osseous lesions in the lumbar vertebrae were made strictly on the basis of the findings of magnetic resonance imaging, computed tomography or plain radiography. Sixteen patients had to be excluded from the study because they did not undergo adequate radiological examination. To determine the particular localisation of vertebral lesions in the bone scan, two experienced nuclear medicine physicians examined the studies independently while blinded to the radiological results. Four anatomical regions were differentiated within the vertebra: the vertebral body, the pedicle, the facet joints and the spinous process. Clopper-Pearson analysis, which takes into account the number of examinations, yielded the following probability intervals for the malignancy of intraosseous lesions in the lumbar spine: vertebral body 36.8%–57.3%, pedicle 87.7%– 100%, facet joints 0.8%–21.4% and spinous process 18.7%–81.3%. It was concluded that lesions affecting the pedicle are a strong indicator for malignancy, whereas involvement of the facet joints is usually related to benign disease. Lesions affecting the vertebral body or the spinous process do not show a clear tendency towards either malignancy or benignity. In contrast to other studies, a significant probability of malignancy (35.6%) was observed in lesions affecting exclusively the vertebral body.

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.

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.

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.

Functional imaging in the assessment of myocardial infarction: MR imaging vs. MDCT vs. SPECT

PURPOSE To intraindividually compare magnetic resonance (MR) imaging, ECG-gated multi-detector spiral computed tomography (MDCT) and gated single photon emission computed tomography (SPECT) for the evaluation of global and regional myocardial function and the identification of myocardial perfusion abnormalities. MATERIALS AND METHODS Nine patients (8 men; 55.1+/-8.9 years) with a history of myocardial infarction (MI) were included in this retrospective study. All patients had undergone segmented k-space steady state free precession MR imaging, (99m)Tc-MIBI gated myocardial perfusion SPECT and contrast enhanced ECG-gated 16-MDCT. Ventricular volumes and ejection fraction (EF) were calculated. Left ventricular (LV) wall motion at rest was analyzed. For SPECT and arterial phase MDCT perfusion abnormalities were assessed. Data was compared with Lins concordance-correlation coefficient (rho(c)), Bland-Altman plots and kappa statistics. RESULTS For EF, there was an excellent concordance and correlation (rho(c)=0.99) between SPECT (EF=41.7+/-10.4%), MDCT (EF=42.2+/-11.1%), and MR imaging (EF=41.9+/-11.4%). Considering MR imaging as standard of reference, MDCT (kappa=0.86) is superior to SPECT (kappa=0.51) for the assessment of the regional wall motion at rest. There was a good agreement between SPECT and MDCT regarding the detection of perfusion abnormalities (kappa=0.62). CONCLUSION MDCT, MR imaging, and SPECT allow for the reliable assessment of global and regional left ventricular function in patients with a history of MI. MDCT also allows to some extent for the detection of perfusion abnormalities. With its potential to assess both, the coronary arteries as well as the myocardium, MDCT a promising modality for the comprehensive diagnostic work-up in patients with suspected myocardial ischemia.

To PIOPED, or Not to PIOPED

For the last 15 years, the development of lung scintigraphy has been closely connected with the PIOPED studies. In the latest analysis based on the PIOPED II data, published in this issue of The Journal of Nuclear Medicine (1), we learn that chest radiography may safely be substituted for the ventilation scan. However, I have to admit that I am not completely convinced of the usefulness of the PIOPED system itself. In fact, I am of the opinion that the PIOPED classification, with all its nondiagnostic cases, its intermediate-probability class, and its unfavorable complexity, led to the decline of ventilation–perfusion (V/Q) scintigraphy that we are experiencing

Mediastinal staging of lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography and a dual-head coincidence gamma camera.

Abstract. The aims of the present study were (a) to evaluate mediastinal staging in patients with lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) using a coincidence gamma camera (hybrid PET) in comparison with dedicated positron emission tomography (PET) and computed tomography (CT), and (b) to assess the feasibility to determine standardized uptake values (SUV) with hybrid PET. Forty patients were included in the study. Hybrid PET was performed without and with attenuation correction. Data were rebinned with single-slice (SSRB) or Fourier rebinning (FORE). The SUVs of primary tumors were calculated with hybrid PET and compared with SUVs determined by dedicated PET. Diagnostic accuracy for hybrid with or without attenuation correction was 80 or 74% compared with 82% for dedicated PET, and 63% for CT. Attenuation-corrected hybrid PET revealed a higher specificity than CT (83 vs 52%; p<0.05). The SUVs of primary tumors were similar to those of hybrid PET and dedicated PET with a mean relative difference of 20.8±16.4%. The FORE improved the agreement of SUVs with a mean relative difference of 13.8±9.9 vs 36.0±17.9% for SSRB (p<0.001). Hybrid PET with attenuation correction is more specific than CT for mediastinal staging in patients with lung cancer (p<0.05). It reveals similar results in comparison with dedicated PET. Calculation of SUVs with hybrid PET is feasible.

Sequential (gemcitabine/vinorelbine) and concurrent (gemcitabine) radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study

BackgroundThe aim of the study was to determine the maximal tolerated dose (MTD) of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC) and to evaluate the efficacy of this regime in a phase II study.Methods33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patients were assessable for evaluation of toxicity and tumor response. Treatment included two cycles of induction chemotherapy with gemcitabine (1200 mg/m2) and vinorelbine (30 mg/m2) at day 1, 8 and 22, 29 followed by concurrent radiotherapy (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every two weeks at day 43, 57 and 71. Radiotherapy planning included [18F] fluorodeoxyglucose positron emission tomography (FDG PET) based target volume definition. 10 patients were included in the phase I study with an initial gemcitabine dose of 300 mg/m2. The dose of gemcitabine was increased in steps of 100 mg/m2 until the MTD was realized.ResultsMTD was defined for the patient group receiving gemcitabine 500 mg/m2 due to grade 2 (next to grade 3) esophagitis in all patients resulting in a mean body weight loss of 5 kg (SD = 1.4 kg), representing 8% of the initial weight. These patients showed persisting dysphagia 3 to 4 weeks after completing radiotherapy. In accordance with expected complications as esophagitis, dysphagia and odynophagia, we defined the MTD at this dose level, although no dose limiting toxicity (DLT) grade 3 was reached.In the phase I/II median follow-up was 15.7 months (4.1 to 42.6 months). The overall response rate after completion of therapy was 64%. The median overall survival was 19.9 (95% CI: [10.1; 29.7]) months for all eligible patients. The median disease-free survival for all patients was 8.7 (95% CI: [2.7; 14.6]) months.ConclusionAfter induction chemotherapy, the maximum tolerated dose and frequency of gemcitabine was defined at 500 mg/m2 every two weeks in three cycles during a maximum of 7 weeks of thoracic radiotherapy for the phase II study. This regimen represents an effective and tolerable therapy in the treatment of NSCLC.