Michael Zimny

Fluorine-18 fluorodeoxyglucose positron emission tomography in the differential diagnosis of pancreatic carcinoma: a report of 106 cases

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) as a tool for the differential diagnosis of pancreatic carcinoma while taking into account serum glucose level. A group of 106 patients with unclear pancreatic masses were recruited for the study. PET was performed following intravenous administration of an average of 190 MBq [18F]FDG. Focally increased glucose utilisation was used as the criterion of malignancy. In addition, the \ldstandardised uptake value\rd (SUV) was determined 45 min after injection. Carcinoma of the pancreas was demonstrated histologically in 74 cases, and chronic pancreatitis in 32 cases. Employing visual evaluation, 63 of the 74 (85%) pancreatic carcinomas were identified by PET. In 27 of the 32 cases (84%) of chronic pancreatitis il was possible to exclude malignancy. False-negative results (n=11) were obtained mostly in patients with raised serum glucose levels (10 out of 11), and false-positives (n=5) in patients with inflammatory processes of the pancreas. Thus PET showed an overall sensitivity of 85%, a specificity of 84%, a negative predictive value of 71%, and a positive predictive value of 93%. In a subgroup of patients with normal serum glucose levels (n=72), the results were 98%, 84%, 96% and 93%, respectively. Quantitative assessment yielded a mean SUV of 6.4\+-3.6 for pancreatic carcinoma as against a value of 3.6\+-1.7 for chronic pancreatitis (P\s<0.001), without increasing the diagnostic accuracy. This shows PET to be of value in assessing unclear pancreatic masses. The diagnostic accuracy of PET examinations is very dependent on serum glucose levels.

Does positron emission tomography using 18-fluoro-2-deoxyglucose improve clinical staging of testicular cancer?— results of a study in 50 patients

OBJECTIVES To compare positron emission tomography (PET) using 18-fluoro-2-deoxyglucose (FDG) with conventional clinical staging in unselected patients with germ cell cancer. METHODS Fifty patients underwent PET scans of the abdomen (n = 50) and chest (n = 41 ) after the initial diagnosis. PET images were evaluated qualitatively and quantitatively using standardized uptake values (SUVs). The results were compared with computed tomography (CT) results and tumor markers (human chorionic gonadotropin, alpha-fetoprotein, and lactate dehydrogenase). Retroperitoneal lymphadenectomy in 12 patients and clinical staging, including follow-up data in all patients, were taken as a reference standard. RESULTS PET detected metastases in 13 (87%) of 15 patients and excluded metastases in 33 (94%) of 35 patients. A sensitivity of 73% and a specificity of 94% were obtained using CT. The respective values for tumor marker determination were 67% and 100%. Retroperitoneal metastases were detected in 2 patients by PET only and in 1 patient by CT only. In the latter patient, surgery of a residual mass after chemotherapy revealed a well-differentiated teratoma. False-negative findings with PET and CT occurred in 2 patients with retroperitoneal metastases approximately 10 mm in size. False-positive findings were due to sarcoidosis or to muscular activity of the neck. Quantitative FDG uptake was very heterogeneous, with an SUV ranging from 1.8 to 17.3. CONCLUSIONS FDG PET has the potential to improve clinical staging of testicular cancer. However, PET, as well as CT, is limited in the detection of small retroperitoneal lymph node metastases.

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.

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.

Calculation and Validation of a Plasma Calcitonin Limit for Early Detection of Medullary Thyroid Carcinoma in Nodular Thyroid Disease

BACKGROUND The early diagnosis of medullary thyroid carcinoma (MTC) is crucial for effective therapy. Elevated plasma calcitonin concentrations (pCT-Cs) are generally a specific and sensitive indicator for C-cell hyperplasia or MTC. The presence of thyroid nodules raises the possibility of MTC. Hence, in endemic goiter regions, there is a need for information regarding the pCT-C values that are indicative of C-cell hyperplasia or MTC. The aim of this study, therefore, was to determine an upper pCT-C to distinguish patients with and without MTC in a collective with nodular thyroid disease, and to give an estimation of the prevalence of MTC in an endemic goiter area. METHODS Basal pCT-C was measured in 21,928 patients with thyroid nodules living in central Germany, an area with endemic goiter due to previous iodine deficiency. In 218 subjects with pCT-Cs exceeding 10 ng/L, stimulated pCT-C was additionally determined, as suggested by the German consensus recommendation. A nominal normal range for basal pCT-C was calculated with data from 21,900 subjects without known MTC. The predicted upper limit was then validated using the known diagnoses of 376 patients with pCT-Cs exceeding 10 ng/L, 28 of whom presented with MTC. RESULTS For basal pCT-C, calculation of the three-sigma borders after logarithmic transformation revealed upper limits of the nominal normal range of 14.6 ng/L in females and 32.8 ng/L in males, respectively. However, three male patients with small MTCs had basal pCT-Cs between 15 and 33 ng/L. None of the patients with MTC had a basal pCT-C below 15 ng/L or an increase in pCT-C after pentagastrin stimulation that was less than 80 ng/L. In the basal pCT-C range between 15 and 50 ng/L (n = 192; eight with MTC), the positive predictive value for the detection of MTC was 4% in our group. Applying an upper limit for basal pCT-C of 15 ng/L in both sexes, 329 of the total of 21,928 patients exceeded this range. Among these, the final outcome is known in 231 subjects, including all 28 MTCs. CONCLUSIONS An upper limit of 15 ng/L instead of 10 ng/L for basal pCT-C is able to detect all MTC and reduce false-positive cases. The prevalence of MTC in nodular thyroid disease in our group was approximately 1.8 per thousand.

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.

FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast cancer

Breast cancer continues to be one of the most common cancers in North America and Western Europe. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG PET) represents a non-invasive functional imaging modality that is based on metabolic characteristics of malignant tumours. In breast cancer, FDG PET is more accurate than conventional methods for staging of distant metastases or local recurrences and enables early assessment of treatment response in patients undergoing primary chemotherapy. Recent data indicate a rationale for the use of FDG PET in cases of asymptomatically elevated tumour marker levels in the presence of uncertain results of conventional imaging. Despite the fact that PET cannot rule out microscopic disease, it does have particular value in providing, in a single examination, a reliable assessment of the true extent of the disease. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the assessment of asymptomatic patients with elevated tumour marker levels. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance.

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.

”Ecstasy”-induced changes of cerebral glucose metabolism and their correlation to acute psychopathology

Abstract. The aim of this study was to determine the acute effects of the ”Ecstasy” analogue MDE (3,4-methylene dioxyethamphetamine) on cerebral glucose metabolism (rMRGlu) of healthy volunteers and to correlate neurometabolism with acute psychopathology. In a randomized double-blind trial, 15 healthy volunteers without a history of drug abuse were examined with fluorine-18-deoxyglucose (18FDG) positron emission tomography (PET) 110–120 min after oral administration of 2 mg/kg MDE (n=7) or placebo (n=8). Two minutes prior to radiotracer injection, constant cognitive stimulation was started and maintained for 32 min using a word repetition paradigm to ensure constant and comparable mental conditions during cerebral glucose uptake. Individual brain anatomy was represented using T1-weighted 3D flash magnetic resonance imaging (MRI), followed by manual regionalization into 108 regions of interest and PET/MRI overlay. After absolute quantification of rMRGlu and normalization to global metabolism, normalized rMRGlu under MDE was compared to placebo using the Mann-Whitney U-test. Acute psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and rMRGlu was correlated to PANSS scores according to Spearman. MDE subjects showed significantly decreased rMRGlu in the bilateral frontal cortex: left frontal posterior (–7.1%, P<0.05) and right prefrontal superior (–4.6%, P<0.05). On the other hand, rMRGlu was significantly increased in the bilateral cerebellum (right: +10.1%, P<0.05; left: +7.6%, P<0.05) and in the right putamen (+6.2%, P<0.05). There were positive correlations between rMRGlu in the middle right cingulate and grandiosity (r=0.87, P<0.05), both the right amygdala (r=0.90, P<0.01) and the left posterior cingulate (r=0.90, P<0.01) to difficulties in abstract thinking, and the right frontal inferior (r=0.85, P<0.05), right anterior cingulate (r=0.93, P<0.01), and left anterior cingulate (r=0.85, P<0.05) to attentional deficits. A negative correlation was found between the left frontal operculum (Broca’s area) and attentional deficits (r=–0.85, P<0.05). The present study revealed acute neurometabolic changes under the ”Ecstasy” analogue MDE, indicating a frontostriatocerebellar imbalance paralleling other psychotropic substances or various psychiatric disorders.

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.