Andreas Helisch

Noninvasive assessment of Crohn's disease activity: a comparison of 18F-fluorodeoxyglucose positron emission tomography, hydromagnetic resonance imaging, and granulocyte scintigraphy with labeled antibodies.

OBJECTIVES:Detection of disease activity in Crohns disease (CD) is of crucial importance for diagnosis and management of the disease. Noninvasive methods for monitoring are desirable and comprise hydromagnetic resonance imaging (hydro-MRI) and leukocyte scintigraphy. In addition, a recent case report indicated the potential of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to assess CD activity. However, comparative prospective studies are lacking.METHODS:Between February, 1999 and August, 2000, 59 patients with CD were enrolled in a prospective study to assess disease activity by FDG-PET, hydro-MRI, and immunoscintigraphy with anti-nonspecific cross-reacting antigen 95 antigranulocyte antibodies. In 28 of these patients, colonoscopy could be performed. Twelve patients with irritable bowel syndrome and 20 tumor patients without gut inflammation served as controls. Results were compared by statistical analysis.RESULTS:FDG-PET detected 127 pathological findings (average maximum standardized uptake value = 4.4 ± 1.1) in the terminal/neoterminal ileum (37), small bowel (24), and colon (66) of 54 patients with CD, whereas no pathological findings were seen in five patients with CD, the control patients with irritable bowel syndrome, and the tumor patients without gut inflammation. In contrast, examination with hydro-MRI or granulocyte antibodies detected less pathological findings in CD patients. Forty-five of the detected foci were accessible to endoscopic verification. The correlation of the foci with endoscopic findings showed a high specificity (>89%) of all three methods to detect inflamed areas in the terminal ileum and colon of patients with CD, although analyses by hydro-MRI and granulocyte antibody scan had strikingly lower sensitivities (40.9% and 66.7%) than FDG-PET analysis (85.4%).CONCLUSIONS:FDG-PET appears to be a reliable noninvasive tool for simultaneous detection of inflamed areas in the small and large bowel of patients with CD. FDG-PET can be used to detect disease activity in the terminal ileum and colon of CD patients with high sensitivity and specificity.

6-18F-fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to 123I-metaiodobenzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocytomas and paragangliomas: correlation with vesicular monoamine transporter expression.

CONTEXT Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by (18)F-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than (123)I-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy. OBJECTIVE The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings. DESIGN AND SETTING Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study. PATIENTS Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate dehydrogenase complex, subunit D, two succinate dehydrogenase complex, subunit B, one von Hippel Lindau tumor suppressor protein, two Neurofibromatosis-1), and 12 of 25 were classified as sporadic. Five patients had hormonally inactive adrenal incidentalomas. MAIN OUTCOME MEASURES In all patients computed tomography scan and/or magnetic resonance imaging as well as both 123-I-MIBG scintigraphy and FDOPA-PET were performed. Resected tumors were examined by immunohistochemistry for expression of the vesicular monoamine transporter (VMAT)-1 and -2 and other markers. RESULTS A total of 64 lesions were found with both functional imaging modalities. FDOPA-PET detected 62 lesions, whereas only 34 lesions were detected by 123-I-MIBG scintigraphy. This resulted in an overall sensitivity and specificity for FDOPA-PET of 98 and 100% and for MIBG of 53 and 91%, respectively. Comparable sensitivities were found for adrenal and extraadrenal abdominal lesions (94 vs. 97%), whereas in thoracic/cervical lesions, the sensitivity for 123-I-MIBG scintigraphy (15%) was inferior to that of FDOPA-PET imaging (100%). Immunohistochemistry demonstrated a lack of VMAT-1 expression in all MIBG-negative tumors. Clinical predictors for MIBG negativity were a predominant norepinephrine/normetanephrine secretion, an age less than 45 yr, and a hereditary cause. CONCLUSION FDOPA-PET is superior to 123-I-MIBG scintigraphy in patients with extraadrenal, predominantly noradrenaline-secreting, and hereditary types of PHEO/PGL. The lack of VMAT-1 expression predicts negativity for MIBG-scintigraphy.

Subtypes of negative symptoms: The primary subtype in schizophrenic and non-schizophrenic patients

1. The specificity of negative symptoms remains an open question and requires further research. 2. Subtyping negative symptoms has been showed to be a very relevant point for the identification of primary negative symptoms and for their pharmacotherapy. Negative symptoms as a whole have been demonstrated in schizophrenic and non-schizophrenic patients, but these studies did not report about the primary and secondary subtypes. 3. The present study is the first one investigating primary negative symptoms in schizophrenic and non-schizophrenic patients. 84 consecutively admitted psychiatric patients have been studied 5 years after their discharge. 4. All negative symptoms (including the primary subtype) according to Carpenter (Kirkpatrick et al. 1989) and Andreasen (Andreasen 1981) could be identified in all diagnostic groups.

Synthesis and preliminary evaluation of (R,R)(S,S) 5-(2-(2-[4-(2-[18F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol ([18F]FEFE) for the in vivo visualisation and quantification of the β2-adrenergic receptor status in lung

The (18)F-labeled beta2-adrenergic receptor ligand (R,R)(S,S) 5-(2-(2-[4-(2-[(18)F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol, a derivative of the original highly selective racemic fenoterol, was synthesized in an overall radiochemical yield of 20% after 65 min with a radiochemical purity higher than 98%. The specific activity was in the range of 50-60 GBq/micromol. In vitro testing of the non-radioactive fluorinated fenoterol derivative with isolated guinea pig trachea was conducted to obtain an IC(50) value of 60 nM. Preliminary ex vivo organ distribution and in vivo experiments with positron emission tomography (PET) on guinea pigs were performed to study the biodistribution as well as the displacement of the radiotracer to prove specific binding to the beta2-receptor.

Surveillance of basaloid oral squamous cell carcinoma: the value of [18F]FDG-PET.

Basaloid squamous cell carcinoma (BSCC) represents a rare but exceptionally aggressive variant of oral cancer. Hence, when tumors have been characterized to belong to this specific high-risk subpopulation, it remains an open issue how to manage the patients in terms of diagnostic surveillance and reconstruction. Therefore we explored whether glucose metabolism as measured by [18F]FDG-PET can accurately assess the disease status in the follow up of oral BSCC. The data of four patients with pathologically proven BSCC were analyzed in this study. These patients had [18F]FDG-PET scans after curative therapy to screen for local recurrence or disease generalization. The [18F]FDG-PET findings were correlated with clinical outcome. [18F]FDG-PET identified a site of recurrent tumor that was invisible to morphological imaging. None of the three patients with a normalized pattern of glucose uptake had secondary tumor progress within the further follow up period. Thus, [18F]FDG-PET proved valuable to identify those patients who will profit from early onset of reconstruction measures even though they originally belonged to a high-risk population.

Small animal tumour imaging with MRI and the ECAT EXACT scanner: application of partial volume correction and comparison with microPET data.

ObjectivePartial volume effects caused by limited spatial resolution of conventional positron emission tomography (PET) scanners result in an underestimation of the activity concentration in small tumours. The aim of the study was to evaluate the feasibility of small animal tumour imaging with the clinical PET scanner ECAT EXACT after partial volume correction based on MRI calculations. The same tumour model was examined additionally with the small animal PET system, microPET focus 120. MethodsBefore the ECAT EXACT studies recovery coefficients for different sphere volumes were generated with phantom experiments. For the following in-vivo study DS-sarcoma cells were implanted on both hind foot dorsum of male Sprague–Dawley rats. In-vivo tumour volume calculations were done with the high-resolution MRI system, Magnetom Vision Experimental. Dynamic 18F-fluorodeoxyglucose (FDG) PET was performed with the scanner ECAT EXACT (5 MBq intravenous, two-dimensional mode, n = 16 tumours) or with the microPET focus 120 (20 MBq intravenous, two-dimensional mode, n = 10 tumours). The animals were then killed, the tumours rapidly explanted, weighed and homogenized. The concentration of 18F-FDG was measured with a &ggr; counter and decay corrected; the ex-vivo 18F-FDG concentration was compared with the mean tumour activity concentration of the PET data. ResultsUsing the ECAT EXACT mean underestimation of actual tumour 18F-FDG concentration was 35.4%, for partial volume-corrected data this error decreased to 1.7%. In addition, after partial volume correction congruence and linear correlation between the regions of interest-based activity concentration and ex-vivo measurements were excellent (r = 0.98). These results were quite similar to the microPET experiments without partial volume correction: r = 0.99. ConclusionThese data indicate that partial volume correction might allow use of the clinical PET system, ECAT EXACT, for the metabolic assessment of small animal tumours ≥10 mm with sufficient accuracy if no dedicated animal PET is available.

Critical single proximal left arterial descending coronary artery stenosis to mimic chronic myocardial ischemia: a new model induced by minimal invasive technology.

Background/Aims: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth. Methods: Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine. Seven animals were examined by nuclear PET and SPECT analysis. Epi-, mid- and endocardial fibrosis and the numbers of arterial vessels were examined by histology. Results: Functional analysis showed a significant decrease in global left ventricular ejection fraction (24.5 ± 1.6%) 3 weeks after implantation. There was a trend to increased left ventricular ejection fraction after low-dose dobutamine stress (36.0 ± 6.6%) and a significant improvement of the impaired regional anterior wall motion. PET and SPECT imaging documented chronic hibernation. Myocardial fibrosis increased significantly in the ischemic area with a gradient from epi- to endocardial. The number of arterial vessels in the ischemic area increased and coronary angiography showed abundant collateral vessels of Rentrop class 1. Conclusion: The presented experimental model mimics the clinical situation of chronic myocardial ischemia secondary to 1-vessel coronary disease.

Negative Symptoms and the Course of Positive Symptoms in Deficit Schizophrenia

Differences in the patterns of negative symptoms between two subgroups of inpatients with chronic schizophrenia and a deficit syndrome were examined: one subgroup presented episodic symptoms, while the other exhibited a continuous course of positive symptoms. Patients with a continuous course of positive symptoms showed significantly higher affective blunting and anhedonia according to the SANS, a lower BPRS activation score and a lower age of onset in males than episodic cases. These results suggest that in deficit schizophrenia different courses of positive symptoms are associated with different severity degrees and different patterns of negative symptoms.

One single-time-point kidney uptake from OctreoScan correlates with number of desintegrations measured over 72 hours and calculated for the 6.7 hours half-life nuclide (177)Lu.

Aim In somatostatin receptor-targeted therapy, renal toxicity is an expected side effect, and therefore pretherapeutic dosimetry based on a measured kinetics is preferable. In contrast, a convenient one single-time-point scan might also reveal relevant information on expected dose to organs. However, very early time points might not reflect the true retention by the renal cortex and therefore be of limited value to predict dose for the long-lived 177Lu. Patients and Methods Dosimetry with 111In-octreotide was performed in 24 patients, and the number of disintegrations (ND) were calculated for 177Lu. Uptake values for each time point were correlated with ND. Results The fitting algorithm was best with biexponential equations in 18 patients. Mean biologic half-life of the alpha component was 6 hours (+/−12 hours) and for the beta component 82 hours (+/−38 hours). For the early time points, correlation with ND was generally poor. For later time points, correlation increased markedly after 4 hours (4 hours: r = 0.83, 72 hours: r = 0.93) and were also capable of predicting dosimetry to some extent. Conclusion In conclusion, thorough quantification of the 4 hours single-time-point scans seems to be enough to predict the expected renal dose for radionuclide therapies to some degree.

Primäre Negativsymptomatik und Verlauf psychiatrischer Störungen

Schon vor der Ara der Negativsymptomatik war die Vorhersage von defizitaren Symptomen bei psychotischen Patienten im Einzelfall nicht moglich. Eine Zusammenfassung wichtiger Verlaufstudien findet man bei Harding (1988). Die Negativsymptomatik ist ein relativ neues Gebiet zur Erforschung von schizophrenen Defiziten und erweckte durch Operationalisierung und Quantifizierbarheit neue Hoffnung auf diesem Gebiet. Die Zusammenhange zwischen Positiv- und Negativsympotmatik haben zunehmend an Aufmerksamkeit gewonnen und bleiben ein umstrittenes Gebiet (Fenton et al. 1991). Langschnittuntersuchungen konzentrierten sich bislang vorwiegend auf den Beginn der Symptomatik (Pfohl et al. 1982), ihre Verlaufsart (Gerbaldo et al. 1995), ihre Pravalenz (McCreadi et al. 1989) oder ihre Stabilitat (Marneros et al. 1995) wahrend der letzten 10 Tage (Harvey et al. 1984) 7, 2 oder 5 Jahre. Die Minussymptomatik ist als fluktuierend (Wing und Brown 1970), zunehmend (Biehl et al. 1989), oder abnehmend (Pogue-Geile et al. 1985) beschrieben worden. Andere Studien berichten uber keine Assoziation zwischen positiver und Defizitsymptomatik (Fenton et al. 1994), Dauer der Storung, Hostitalisierungsdauer oder Episodendauer (Kay 1989). Trotzdem wurde der Gesamtdauer der psychotischen Symptomatik bislang wenig Aufmerksamkeit gewidmet. Die potentielle Rolle solcher Studien wurde bereits betont (Carpenter et al. 1988). Der Zusammenhang zwischen der Dauer der psychotischen Symptomatik, der Episodenzahl, und des Defizitsyndroms wurde von uns funf Jahre nach Entlassung untersucht.