[Ga-68-PSMA PET/CT for prostate cancer]. / Ga-68-PSMA-PET/CT bei Prostatakarzinom.

Prostate-specific membrane antigen (PSMA) is expressed as a cell surface protein physiologically in the prostate and can be found in all stages of prostate cancer. Even in castration-resistant prostate cancers, this overexpression of PSMA occurs. Due to the enzymatic activity of PSMA it was possible develop specific inhibitors from which "small molecule" radiopharmaceuticals were derived. By coupling the specific binding motif glutamate-urea-lysine with the chelator HBED-CC, which complexes Ga-68 very effectively, a new radiopharmaceutical is available for Ga-68-PSMA-PET/CT. According to the first results in patients with prostate carcinoma, this new diagnostic tool exhibited advantages in image quality compared to choline-PET/CT. An initial study demonstrated the higher contrast of the PET signal and an improved diagnostic accuracy. The properties of even further new PSMA PET radiopharmaceuticals can be of increasing importance for the diagnostic work-up of prostate cancer in all stages. In conjunction with therapeutic PSMA radiopharmaceuticals, a new field of theragnostics is opened.

Diagnostic and therapeutic use of membrane proteins in cancer cells.

As proteomics technologies develop, increasing number of membrane-associated proteins specific for cancer cells are being discovered. These proteins are of great interest, particularly because they are rich in targets for antibodies. Amongst them candidate biomarkers for early tumor diagnosis, prognosis and treatment have been detected. The suitability of several membrane-associated proteins as targets for drugs or antibodies has already been tested in preclinical and clinical studies. The results were encouraging in some cases, but not in all. They demonstrate that each type of tumor has its specific "Achilles heel", and that suitable targets of cancer diagnosis and therapy must be found for each kind of neoplasm. This implies that membrane-associated proteins for each type of tumor cell need to be investigated. This review describes the current technologies of membrane protein characterization in a first part and subsequently summarizes the membrane associated proteins currently being tested as targets for diagnosis and treatment in breast, prostate, thyroid, and colon cancer. Their function will be explained and their role in tumor biology will be discussed.

Papillary microcarcinoma and papillary cancer of the thyroid

AIMS: Major controversies exist regarding the treatment of papillary microcarcinoma of the thyroid (PMC). Prior to 2003 PMC was defined by the WHO as a papillary carcinoma of 1 cm or less in diameter. In 2004 that definition changed, with the new classification requiring that the tumour also must be found incidentally. PATIENTS, METHODS: In this study we reviewed the clinical records of 67 patients with papillary tumours of the thyroid

Mechanisms of regional wall motion abnormalities in contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: In the diagnosis of coronary artery disease (CAD) with Dobutamine Stress Echocardiography (DSE), regional wall motion abnormalities (RWMA) are assumed to indicate a perfusion deficit. METHODS AND RESULTS: For a more particular examination of RWMAs, we compared simultaneous echo-contrast (Optisone)-enhanced DSE (0-40 microg/kg Dobutamine, 16-segment- model) and MiBi-SPECT in a prospective double-blinded study design in 69 non-selected consecutive patients (44 male, 25 female, age 64+/-12 years). Additionally, all patients were examined by coronary-angiography. The prevalence of significant CAD (stenosis >50% lumen diameter) was 52%. DSE had a sensitivity of 78% and a specificity of 66% for the detection of significant CAD with a positive and negative predictive value of 72 and 73%, respectively. Among 28 patients with significant CAD and positive DSE study (true positive), 78% displayed a corresponding perfusion deficit in MiBi-SPECT. Among 11 patients with a positive DSE study but no current significant coronary stenosis (false positive), 82% showed stress-induced RWMAs in the inferior/posterior region, 73% displayed left ventricular hypertrophy, 54% resting-ECG abnormalities and 45% resting-RWMA (3 previous MI, 2 previous CABG surgery). Among 8 patients with negative DSE study but significant coronary stenosis (false negative), 75% had a stenosis of the LCX, 63% displayed resting- WMA, 63% displayed left bundle branch block or ST-segment depression, 50% displayed only peripheral coronary stenosis, and DSE visualization was suboptimal in 38%. CONCLUSION: This prospective study in non-selected patients shows that the majority of RWMAs in DSE are matched to a perfusion deficit detectable by nuclear imaging. Nevertheless, pre-existing cardiac abnormalities may also lead to stress-induced RWMA not associated with a perfusion deficit or mask a perfusion deficit upon DSE. Particularly in patients with LV hypertrophy, resting-RWMA, bundle branch block or ST segment depression, the predictive value of DSE may, therefore, be limited.

Vasculitis of the aortic arch and cardiac valves as the cause of relapsing fever of unknown origin in an elderly, white man.

Here, we report the case of fever of unknown origin (FUO) in a 77-year-old white man. The patient presented with a 3-week history of fever (between 38.5 and 39 degrees C) and general malaise. These symptoms had occurred about five to seven times during the past 30 years, and despite repeated hospitalizations, no diagnosis was made. Physical examination did not reveal any specific signs of infection nor did the patient fulfill the criteria for any rheumatic disease including vasculitides. Blood chemistry showed a greatly elevated C-reactive protein (CRP; 158.2 mg/l) and an erythrocyte sedimentation rate >100 mm, indicating an active inflammatory process, and leukocytes were significantly elevated (20,000/mul). Rheumatological parameters showed only nonspecific changes. Finally, a 2-[(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography was performed, revealing a markedly enhanced glucose uptake in the ascending aorta and the cardiac valves, indicating vasculitis as the cause of FUO in this patient. Based on this finding, treatment was started with corticosteroids, and 2 days after the initiation of treatment, the patient had normal body temperature, and after 5 days, CRP values had returned to normal. After tapering and final complete removal of steroid treatment, the patient was still free of symptoms, hence no disease-modifying antirheumatic drug therapy was necessary.

Time course of cardiac structural, functional and electrical changes in asymptomatic patients after myocardial infarction: their inter-relation and prognostic impact.

OBJECTIVES: We prospectively studied the relationship between left ventricular (LV) dilation, dysfunction, electrical instability and death in patients after a first myocardial infarction (MI) without symptoms of heart failure and ischemia. BACKGROUND: Mechanisms linking LV dysfunction and sudden death in patients after MI remained controversial. METHODS: Left ventricular volumes, hemodynamics, electrocardiogram and 24-h Holter recordings were sequentially obtained between two days and seven years after MI. Left ventricular catheterization and coronary angiography were performed, and revascularization was performed if appropriate. RESULTS: Death occurred in 16 (12%) of the 134 patients included; it was of cardiac origin in 14 (88%) and sudden in origin in 12 (75%) patients. Of 37 (28%) patients with LV dilation, 12 died (32%); four patients (5.8%) died in the group without dilation. Left ventricular dilation was closely related to signs of electrical instability, as indicated by a significant correlation between end-diastolic LV volume index, Lown score (r = 0.98, p < 0.0001) and QTc prolongation (r = 0.998, p < 0.01), respectively. CONCLUSIONS: Patients with progressive remodeling are at increased risk of sudden death in chronic MI. Cardiac electrical instability is closely related to progressive LV dilation. Parameters of electrical instability and remodeling are predictors of sudden death. The findings suggest that remodeling might serve as a link between dysfunction, electrical instability of the heart and sudden death after MI.

Effect of quinapril initiated during progressive remodeling in asymptomatic patients with healed myocardial infarction.

Approximately 20% of patients with healed myocardial infarction develop asymptomatic progressive left ventricular (LV) dilation and remodeling and are at increased risk for progression to symptomatic congestive heart failure and premature death. It was the goal of this study to test whether quinapril may interrupt this process and to analyze potential mechanisms. Of 138 patients with an average infarct age of 56 months, 25 had asymptomatic progressive LV dilation and were randomized in a prospective, double-blind study to placebo or quinapril. At baseline (mean +/- SEM) ejection fraction was reduced (35 +/- 3% and 39 +/- 3%) and end-diastolic volume (gated single-photon emission computed tomography) increased (104 +/- 9 and 117 +/- 12 ml/m(2)) with placebo (n = 13) and quinapril (n = 12), respectively. Progressive dilation continued in patients taking placebo (6 months: 9.4 +/- 5.2 ml/m(2), 12 months 24.6 +/- 5. 4 ml/m(2); change from baseline: p <0.05 vs baseline; p <0.05 vs 6 months), but not with quinapril (6 months: -0.9 +/- 4.0 ml/m(2); 12 months: 4.1 +/- 5.2 ml/m(2) [p <0.05] vs placebo). Wedge pressure during bicycle exercise was similar at baseline, but at 12 months tended to be lower with quinapril (17 +/- 1 mm Hg) than with placebo (24 +/- 4 mm Hg, p = 0.1673). Thus, quinapril prevented further progression of asymptomatic LV dilation and remodeling after remote myocardial infarction, possibly due to attenuation of an exercise-induced increase in LV filling pressure.

Establishment and characterization of the follicular thyroid carcinoma cell line ML-1.

The present study focuses on the establishment and characterization of a new follicular thyroid carcinoma cell line. The human cell line ML-1 was derived from a dedifferentiated follicular thyroid carcinoma relapse, which progressed despite preceding surgery followed by two radioiodine therapies. More than 90% of the cells of this line express thyroglobulin, chondroitin sulfate, and vimentin antigens, but only about 70% show cytokeratin filaments and a negative surface charge density such as human erythrocytes. More importantly, cells of this line are able to take up iodine and/or glucose both in vitro and in vivo and to secrete thyroglobulin, chondroitin sulfate, and fibronectin into the interstitial space. In addition, triiodothyronine is released constitutively into culture supernatants. Moreover, it is also suitable for xenotransplantation studies because it is tumorigenic in NMRI nude mice in vivo. The cell line forms tumors with follicular structures when transplanted to nude mice. Due to these unique features the ML-1 cell line can be considered as a very suitable test model for pharmacological and cell biological studies. Since chemicals may interfere with the production of thyroid hormones, this cell line represents also a tool for toxicological investigations.

[The ultrasound centre as a medically and economically relevant alternative--a report of the Regensburg experience]. / Das Ultraschallzentrum als ökonomisch und medizinisch sinnvolle Alternative--ein Erfahrungsbericht über das Regensburger Modell.

In most medical centres, ultrasonography is performed independently by several departments. In october 1997, the University hospital of Regensburg founded an ultrasound centre, integrating surgical and medical departments as well as the institutes for radiology and nuclear medicine. The aims of this centre were the concentration of organization, machines, financial resources, manpower and know-how, standardized training and quality, and strengthening of interdisciplinary cooperation in clinic, medical education and research. Booking, standardized reports and a joint archiving of reports are assisted by a collective computer system. Most examinations in the centre are performed by three all-day present gastroenterology, surgery and radiology residents who are supported by licensed sonographers of the other departments. Training is standardized, and the certification for ultrasound examinations is acquired after a test with theoretical and practical parts. The integration of various departments in the ultra-sound on-call service has led to significant savings. The pool of ultrasound machines is used jointly, department-specific resources for new machines have been put together. We are convinced that this way of a close interdisciplinary cooperation will result in improvements in quality, utilization of financial resources and clinical research.

[Brain SPECT using Tc-99m-bicisate (ECD) in rapidly progressive dementia syndrome]. / Hirn-SPECT mit Tc-99m-Bicisat (ECD) bei rasch progredientem dementiellen Syndrom.

We present a 61-year-old male patient with progressive dementia. A brain SPECT with Tc-99m-bicisate was performed for confirmation of clinically suspected Alzheimer-dementia. At the time of the SPECT-investigation marked apraxia and aphasia besides severe dementia were present. Electrophysiological as well as anatomical neuroimaging findings showed non-diagnostic alterations. SPECT revealed distinct perfusion defects, which made Alzheimer Dementia unlikely. The further course of the patient was determined by rapidly progressive deterioration with development of akinetic mutism. Thereafter, increased levels of neuron-specific enolase as well as 14-3-3 proteins were found in the cerebro-spinal fluid (CSF). The patient finally died with signs of cerebral decortication. Due to the clinical course and the CSF-findings the patient's final diagnosis was Creutzfeldt-Jakob-disease, nevertheless no autopsy was performed. The presented case report underscores the clinical utility of perfusion brain SPECT in the differential diagnosis of dementias.

Somatostatin receptor scintigraphy in thymoma imaging method and clinical application.

Somatostatin receptor scintigraphy with 111In-[DTPA-D-Phe1]-octreotide has the potential for visualizing primary and recurrent thymomas in patients with myasthenia gravis, whereas thymic hyperplasias fail to accumulate somatostatin analog peptides. We demonstrate somatostatin receptor imaging findings in a patient with a mixed encapsulated thymoma which exhibited intense 111In-[DTPA-D-Phe1]-octreotide uptake in early and late scans. In another patient with a history of malignant thymoma 111In-[DTPA-D-Phe1]-octreotide accumulation was clearly seen in a mass suspected to be a recurrence. This paper describes the imaging protocol including Single Photon Emission Computed Tomography (SPECT) and discusses the clinical applications of this feasible functional imaging method in patients with thymomas.

Follow-up findings in regional cerebral blood flow (r-CBF)-SPECT in a case of idiopathic childhood hemidystonia. Functional neuroimaging and pathophysiological implications.

A 9 1/2-year-old girl suffered from intermitting tremor and jitteriness of her left hand and oral muscles every 4 to 6 weeks with long lasting episodes. Clinically myoclonias and dystonic positioning of the left arm, hand and facial muscles were seen. No evidence of trauma, infection or inborn errors of metabolism was found. Successful therapy with carbamazepine was initiated while L-DOPA failed. An ictal 99m-Tc-HMPAO-SPECT showed severe asymmetry with focal hyperperfusion of the contralateral right thalamus and basal ganglia as well as of the bifrontal cortex, whereas no anatomical lesions were found by MRI. In contrast, an interictally performed 99m-Tc-HMPAO SPECT showed hypoperfusion of the right thalamus and normalisation of the frontal perfusion under medical treatment. These 99m-Tc-HMPAO-SPECT findings may provide new insights into the localisation and pathophysiological pathways of idiopathic childhood dystonia.

Quantitative whole body scintigraphy--a simplified approach.

In this paper we present investigations on a simplified method of quantitative whole body scintigraphy by using a dual head LFOV-gamma camera and a calibration algorithm without the need of additional attenuation or scatter correction. Validation of this approach to the anthropomorphic phantom as well as in patient studies showed a high accuracy concerning quantification of whole body activity (102.8% and 97.72%, resp.), by contrast organ activities were recovered with an error range up to 12%. The described method can be easily performed using commercially available software packages and is recommendable especially for quantitative whole body scintigraphy in a clinical setting.

High-resolution SPECT of the temporomandibular joint in chronic craniofacial pain disorders: a pilot study.

Chronic craniofacial pain disorders commonly cause physicians diagnostic difficulties. The purpose of this study was, on one hand, to detect pathological focuses of the craniofacial skeleton using a new system of high-resolution single photon emission computertomography (SPECT), and on the other hand, to compare the results with those obtained via high-field magnetic resonance imaging (MRI) as far as temporomandibular joint affections are concerned. SPECT can be regarded as a supplementary diagnostic mean for patients displaying the symptoms of chronic craniofacial pain disorders, especially in cases where clinical and paraclinical investigations do not coïncide or which are refractory to treatment, not least to differentiate between somatic and psychogenic causes, respectively.

111In-oxine labelling of tumour-cytotoxic macrophages generated in vitro from circulating blood monocytes: an in vitro evaluation.

The labelling of ex-vivo activated macrophages with doses of 111In-oxine sufficient for gamma camera imaging does not damage cell viability or the functional competence of cells (secretion of tumour necrosis factor-alpha and interleukin-6). The mean labelling efficiency was about 84%. Release of 111In equivalent to 15% occurred over 24 h under cell culture conditions, indicating good stability of the radioactive cell label. 111In-oxine-labelled macrophages are a suitable tool for biokinetic studies of adoptive immunotherapy.

[Epidemiology and prognosis of myocardial infarct and chronic heart failure]. / Epidemiologie und Prognose des Myokardinfarktes und der chronischen Herzinsuffizienz.

The incidence of coronary heart disease and myocardial infarction fell gradually during the seventies. Reasons for this decline are not well understood. Speculations include changes of life style and health care. However, cardiovascular disease is still the leader of mortality in Western developed countries. Mortality of myocardial infarction has also declined. The major benefit was associated with broad establishment of coronary care units, smaller steps were achieved by various progresses in medical treatment. In contrast, the incidence of heart failure has increased. The major etiology of heart failure nowadays is coronary heart disease, especially large or recurrent myocardial infarction. The incidence of heart failure in patients having recovered from myocardial infarction is dramatically higher than in normal population. The Framingham Study showed an incidence of 14% in five years following a myocardial infarction. Prognosis of patients with manifestation of symptoms of heart failure is very poor. Patients with heart failure had an overall six years mortality of 55%. These observations suggest that coronary care units, thrombolysis and modern treatment as developed so far, suppressed in-hospital mortality and improved survival for the first year after a myocardial infarction. Thus, patients with larger infarcts who had succumbed early under previous regimens, survived. They carry, however, the burden of severely impaired left ventricular function, high probability to develop heart failure, and of a dubious long-term prognosis. Large efforts have put upon development of scores to estimate long-term prognosis after a myocardial infarction. With the development of techniques, composition of scores changed. However, residual ischemia, major left ventricular dysfunction, and ventricular arrhythmias are the basis of most scores indicating an adverse prognosis after an infarction. This review will be limited to the prognostic impact of left ventricular dysfunction and development of heart failure post myocardial infarction. A hypothetic cascade of events which may lead from myocardial infarction to heart failure and death is schematically outlined in Figure 1. Loss of contractile myocardium results in left ventricular dysfunction which may induce dilatation of the left ventricle, heart failure and ultimately death. This paper focuses on the evidence for the prognostic impact of the single steps and the whole cascade. Figure 1 shows in parenthesis the variables which were frequently measured to assess loss of contractile tissue, left ventricular dysfunction, and dilatation. Since heart failure is understood as a clinical syndrome of symptoms, it may only be semi-quantitated according to the classification of the New York Heart Association (NYHA).(ABSTRACT TRUNCATED AT 400 WORDS)

[Progressive paralysis: prognostic indications by modern imaging procedures. A case report]. / Progressive Paralyse: Prognosehinweise durch moderne bildgebende Verfahren. Ein Fallbeispiel.

The case of a patient with early diagnosed neurosyphilis (general paresis) is presented. Modern neuroimaging techniques such as single photon emission computed tomography (SPECT) may give clues to the treatment outcome as early as 1 month after antibiotic treatment. Improvement of cognitive functions was accompanied by normalization of the initially altered P300-topography.

Adaptation to cardiac dysfunction after myocardial infarction.

Survival after myocardial infarction decreases with left ventricular dilatation, although dilatation at 4 weeks was found to be compensatory. To study this apparent discrepancy, prospective simultaneous volume and hemodynamic measurements at rest were extended in 39 patients with small and 37 with large myocardial infarctions from 4 days (range, 2-6 days) and 4 weeks (range, 3-5 weeks) to 6 months (range, 5-8 months) after infarction and were repeated during supine bicycle exercise at 50 W. In patients with small infarction, end-diastolic volume (mL/m2) decreased from 4 days to 6 months; ejection fraction (%), stroke volume (mL/m2), and end-systolic volume (mL/m2) remained unchanged. Stroke index rose during exercise at 4 weeks and 6 months. In patients after large infarction (n = 37), left ventricular end-systolic volume index (4 days, 38 +/- 3; 4 weeks, 47 +/- 3*; 6 months, 52 +/- 3*; *p < 0.05 versus 4 days) and end-diastolic volume indexes (4 days, 72 +/- 3; 4 weeks, 86 +/- 5*; 6 months, 92 +/- 5*; *p < 0.05 versus 4 days, +p < 0.05 versus 4 weeks) increased at constant wedge pressure. Stroke index remained restored beyond 4 weeks after infarction (4 days, 35 +/- 2; 4 weeks, 42 +/- 2*; 6 months, 42 +/- 2*; p < 0.05 versus 4 days) and rose during exercise at 4 weeks (rest, 45 +/- 2; exercise, 55 +/- 3; p < 0.05) but not at 6 months (rest, 42 +/- 3; exercise, 45 +/- 3; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

T cells migrate to tumour sites after extracorporeal interleukin 2 stimulation and reinfusion in a patient with metastatic melanoma.

Peripheral blood mononuclear cells (PBMC) were taken by leukapheresis from a patient with melanoma skin metastases and stimulated in vitro using 1000 IU recombinant interleukin 2 (IL-2)/ml to generate lymphokine-activated killer cells (LAK cells). Two-colour immunofluorescence analysis demonstrated an IL-2-induced up-regulation of CD25 on natural killer cells (CD56+) as well as on T lymphocytes (CD3+). After radiolabelling with indium-111, the cells were reinfused. Gamma-camera imaging revealed an enrichment at the tumour sites. Immunostaining of tumour tissue taken before and after scintigraphy demonstrated CD25+ T lymphocytes (CD2+, CD3+), but no natural killer cells (CD16+, CD56+) infiltrating the metastases. LAK cell enrichment at melanoma metastases in vivo did not involve natural killer cells, but was characterized by increased numbers of activated T lymphocytes in this patient.