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T M Behr

Publications and source records attributed to T M Behr.

At least 19 recordsLinked to original sources
PubMed2006

Decrease of (99m)Tc-uptake in autonomous thyroid tissue in Germany since the 1970s. Clinical implications for radioiodine therapy.

AIM: The clinical relevance of thyroidal autonomy, i.e. the risk of a patient to become hyperthyroid after exposure to iodine, can be estimated by measurement of the thyroidal (99m)Tc uptake under suppression of TSH (TcTUs). The upper tolerable limit has been set to 2% some 25 years ago. Considering the increase in nutritional iodine uptake over the last 15 years, we wanted to find out if the TcTUs per ml of autonomous volume may have changed. PATIENTS, METHODS: We performed a pilot study in 1166 randomly chosen patients from 1980-2003 with different kinds of benign thyroid disorders to determine changes in TcTU or TcTUs over time. A second analysis was performed in 1063 patients from 1987-2004 with unifocal autonomy (UFA). In these patients, the volume of the autonomous tissue can be determined precisely thus allowing for exact determination of TcTUs per ml of autonomous volume. RESULTS: The pilot study demonstrated that the TcTUs or the TcTU has been falling over the last 25 years in all benign thyroid disorders (p < 0.01). The total thyroid volume has also been decreasing in all disorders. In the second analysis of UFA only, 500 from the 1063 patients fulfilled the inclusion criteria. In these patients, the TcTUs per ml of autonomous volume has fallen from an average of 0.48% to an average of 0.28%. These results are statistically significant as determined by ANOVA testing (p = 0.032). CONCLUSION: As the TcTUs in relation to autonomous volume has dropped by approximately 40% over the last 25 years, the upper limit for a normal TcTUs should be reduced to 1-1.4%, dependent on regional factors.

Biological Transport↗
PubMed2006

What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. PATIENTS, METHODS: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). RESULTS: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n = 143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n = 44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p > 0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76 +/- 80.6 Gy versus 125.6 +/- 46.3 Gy; p < 0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2 +/- 101.7 Gy versus 125.6 +/- 46.3 Gy; p = 0.0097). CONCLUSIONS: TcTUsbased determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm.

Dose-Response Relationship, Radiation↗
PubMed2004

Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT.

REM sleep behaviour disorder (RBD) and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular Parkinson's disease. To investigate the hypothesis that these two clinical features in combination are an indicator of evolving alpha-synucleinopathy, olfactory function was assessed in RBD. We studied 30 patients (18 male, 12 female; mean age 48 +/- 14 years, range 19-78 years) with clinical (idiopathic, n = 6; symptomatic, n = 13, mostly associated with narcolepsy) or subclinical (n = 11, associated with narcolepsy) RBD according to standard criteria and 30 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. RBD patients had a significantly higher olfactory threshold (P = 0.0001), lower discrimination score (P = 0.003), and lower identification score (P = 0.001). Compared with normative data, 97% of the RBD patients had a pathologically increased olfactory threshold, 63% an impaired odour discrimination score, and 63% a decreased identification score. On neurological examination, signs of parkinsonism were newly found in five patients with clinical RBD (not associated with narcolepsy), who usually had a long history of 'idiopathic' RBD. Four of the five patients fulfilled the UK Brain Bank criteria for the clinical diagnosis of Parkinson's disease. The underlying nigrostriatal degeneration of clinical Parkinson's disease was confirmed by I-123-FP-CIT SPECT in one patient and early nigrostriatal degeneration was identified by SPECT in a further two patients with 'idiopathic' clinical RBD out of 11 RBD patients who agreed to undergo SPECT studies. Our study shows that RBD patients have a profound impairment of olfactory function. Five patients with clinical RBD not associated with narcolepsy had clinical or imaging signs of nigrostriatal degeneration. This new clinical finding correlates with the neuropathological staging of Parkinson's disease (stages 1-3) as proposed by Braak. In stage 1, the anterior olfactory nucleus or the olfactory bulb is affected (along with the dorsal motor nucleus of the glossopharyngeal and vagal nerves). In stage 2, additional lesions consistently remain confined to the medulla oblongata and pontine tegmentum, which are critical areas for RBD. Midbrain lesions are found only in stage 3, in particular degeneration of dopaminergic neurons in the substantia nigra pars compacta. Thus, 'idiopathic' RBD patients with olfactory impairment might present with stage 2 preclinical alpha-synucleinopathy. Since narcoleptic patients are not known to have an increased risk of developing parkinsonism, the pathophysiology and clinical relevance of hyposmia in RBD/narcolepsy patients requires further research.

Adult↗
PubMed2004

Case report: drug interference with MIBG uptake in a patient with metastatic paraganglioma.

Metaiodobenzylguanidine (MIBG) labelled with iodine-131 ((131)I) has become a well established therapeutic tool for inoperable metastastic tumours of paraganglioma. There are different pharmacological substances known to interfere with MIBG-uptake which may result in a false negative MIBG scan. We present the case of a 26-year-old male polytoxicomanic patient with metastatic paraganglioma, who underwent MIBG therapy. During earlier therapies, MIBG uptake in the metastatic lesions was very high. A post-therapeutic whole-body scan subsequent to recent (131)I-MIBG therapy failed to detect the vast majority of metastatic lesions-except for two. (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed metastases with a similar distribution to the initial MIBG scan. The possible reasons for the discrepancy in the findings of the MIBG scans and the (18)F-FDG-PET scan are discussed with special emphasis on drug intake prior to MIBG administration, increased MIBG turn-over and unknown drug mixture interference with MIBG uptake.

3-Iodobenzylguanidine↗
PubMed2004

Development and clinical application of peptide-based radiopharmaceuticals.

Peptide-based radiopharmaceuticals have been introduced into clinical work more than a decade ago. The first and most successful imaging agent to date is the somatostatin analog octreotide. It is used for somatostatin receptor scintigraphy and also receptor-mediated peptide-radiotherapy of neuroendocrine tumors. For in vivo use as radiopharmaceutical, the natural peptide is modified in order to enhance the metabolic stability and to allow stable labeling with a so-called residualizing label. This means, that a radiometal chelator complex bound to a modified peptide stable in serum is internalized into the target cells via a specific receptor. The peptide then undergoes lysosomal degradation leaving the radiometal-chelator complex trapped inside the cell, leading to a high target to background ratio. The successful development of new radiopeptides is thus dependent on modifications of a given natural peptide while preserving the binding affinity for the target receptor(s) at the same time. Other peptides than somatostatin are under development for use as radiopeptides such as Minigastrin, GLP-1, VIP, Substance P, or Neurotensin. Some show very favorable results in clinical trials, like Minigastrin for example. Furthermore, there is increasing interest in peptide-binding sites other than the "classical" receptors for regulatory peptides specifically over-expressed by (neuroendocrine) tumors. In this paper, we provide an overview of the biochemical and radiochemical aspects of radiopeptide development, the current state of clinical use of radiopeptides for diagnosis and therapy of tumors, the current state of development of new compounds, and future developments.

Clinical Trials as Topic↗
PubMed2003

LeukoScan for imaging infection in different clinical settings: a retrospective evaluation and extended review of the literature.

PURPOSE: The aim of the current study was to determine the overall diagnostic accuracy of Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments (LeukoScan) for the routine detection of bone and soft tissue infections in a retrospective evaluation. PATIENTS AND METHODS: 138 patients (63 men, 75 women; mean age, 58.29 +/- 25.38 years) with fever of unknown origin and possible endocarditis (n = 59), infection of arthroplastic joints (n = 20), arthritis (n = 16), peripheral (n = 15) and central bone infections (n = 14), soft tissue infection (n = 6), appendicitis (n = 4), pericarditis (n = 2), or vascular graft infection (n = 2) underwent imaging after injection of 555 to 925 MBq (15 to 25 mCi) Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments (LeukoScan). RESULTS: True-positive results were found in 63 of 81 lesions. The overall sensitivity and specificity were 76% and 84%, respectively. In arthritis, seven of seven foci could be detected, whereas false-negative results were found in infections of the femoral bone in three of nine lesions and in periprosthetic infections of long bones in three of eight lesions. Good results were found in five of six soft-tissue infections, in four of six patients with endocarditis, in three of four atypical cases of appendicitis, in two of two infected vascular grafts, and in one of one patient with pericarditis. Subacute and chronic infections of the spine always showed photopenic areas in eight of eight patients. If photopenic lesions were included as diagnostic criteria, the sensitivity and specificity were 88% and 67%, respectively. CONCLUSIONS: Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments can be used for imaging acute infections of peripheral bones and soft tissues. False-negative results are likely in patients with chronic infections. Sensitivity can be increased while decreasing specificity by including photopenic lesions in the spine as diagnostic criteria for localizing disease.

Adult↗
PubMed2002

18F-FDG hybrid PET in patients with suspected spondylitis.

This study investigated the value of fluorine-18 2'-deoxy-2-fluoro- D-glucose (FDG) imaging with a double-headed gamma camera operated in coincidence (hybrid PET) detection mode in patients with suspected spondylitis. Comparison was made with conventional nuclear medicine imaging modalities and magnetic resonance imaging (MRI). Sixteen patients with suspected spondylitis (nine male, seven female, mean age 59 years) prospectively underwent FDG hybrid PET (296 MBq) and MRI. For intra-individual comparison, the patients were also imaged with technetium-99m methylene diphosphonate (MDP) (555 MBq) ( n=13) and/or gallium-67 citrate (185 MBq) ( n=11). For FDG hybrid PET, two or three transverse scans were performed. Ratios of infected (target) to non-infected (background) (T/B) vertebral bodies were calculated. MR images were obtained of the region of interest. Patients found positive for spondylitis with MRI and/or FDG hybrid PET underwent surgical intervention and histological grading of the individual infected foci. Twelve out of 16 patients were found to be positive for spondylitis. Independent of the grade of infection and the location in the spine, all known infected vertebrae ( n=23, 9 thoracic, 12 lumbar, 2 sacral) were detected by FDG hybrid PET. T/B ratios higher than 1.45+/-0.05 (at 1 h p.i.) were indicative of infectious disease, whereas ratios below this value were found in cases of degenerative change. FDG hybrid PET was superior to MRI in patients who had a history of surgery and suffered from a high-grade infection in combination with paravertebral abscess formation ( n=2; further computed tomography was needed) and in those with low-grade spondylitis ( n=2, no oedema) or discitis ( n=2, mild oedema). False-positive 67Ga citrate images ( n=5: 2 spondylodiscitis, 1 aortitis, 1 pleuritis, 1 pulmonary tuberculosis) and 99mTc-MDP SPET ( n=4: 1 osteoporosis, 2 spondylodiscitis, 1 fracture) were equally well detected by FDG hybrid PET and MRI. No diagnostic problems were seen in the other patients ( n=5). In this study, FDG hybrid PET was superior to MRI, 67Ga citrate and (99m)Tc-MDP, especially in patients with low-grade spondylitis (as compared with MRI), adjacent soft tissue infections (as compared with 67Ga citrate) and advanced bone degeneration (as compared with 99mTc-MDP).

Adult↗
PubMed2002

Follow-up of perfusion defects in pulmonary perfusion scanning after pulmonary embolism: are we too careless?

Persisting perfusion defects may still be found in pulmonary perfusion scintigraphy months or years after pulmonary embolism. The aim of this study was to investigate the rate of persisting perfusion defects and the pattern of scintigraphic follow-up of patients after pulmonary embolism. Only those patients were included into our study who received pulmonary perfusion scintigraphy between 1991 and 1999, and who had perfusion defects including at least one whole segment. These perfusion defects were considered as persisting perfusion defects if unchanged over at least 1 year. From 3640 patients examined, 451 (12.4%) had perfusion defects meeting the criteria of this study. Of those, 129 (28.6%) received a scintigraphic follow-up. In 62 patients (48.1%), a reperfusion of the defects was found. In 38 patients (29.5%), the defects persisted within a follow-up period of up to 12 weeks. However, no pulmonary perfusion scintigraphy was performed thereafter. Out of the 129 patients receiving a scintigraphic follow-up, only 29 (22.5%) had a follow-up over more than 1 year, 19 of those had persisting perfusion defects. It is concluded that our data show an inadequate scintigraphic follow-up of patients with pulmonary embolism which may lead to unnecessary anticoagulant treatment if persisting perfusion defects are misinterpreted as fresh pulmonary embolism. In many cases, there was no further follow-up even if reperfusion of the defects was lacking in early follow-up.

Adult↗
PubMed2001

Hypertensive end-organ damage and premature mortality are p38 mitogen-activated protein kinase-dependent in a rat model of cardiac hypertrophy and dysfunction.

BACKGROUND: Numerous pathological mediators of cardiac hypertrophy (eg, neurohormones, cytokines, and stretch) have been shown to activate p38 MAPK. The purpose of the present study was to examine p38 MAPK activation and the effects of its long-term inhibition in a model of hypertensive cardiac hypertrophy/dysfunction and end-organ damage. METHODS AND RESULTS: In spontaneously hypertensive stroke-prone (SP) rats receiving a high-salt/high-fat diet (SFD), myocardial p38 MAPK was activated persistently during the development of cardiac hypertrophy and inactivated during decompensation. Long-term oral treatment of SFD-SP rats with a selective p38 MAPK inhibitor (SB239063) significantly enhanced survival over an 18-week period compared with the untreated group (100% versus 50%). Periodic echocardiographic analysis revealed a significant reduction in LV hypertrophy and dysfunction in the SB239063-treatment groups. Little or no difference in blood pressure was noted in the treatment or vehicle groups. Basal and stimulated (lipopolysaccharide) plasma tumor necrosis factor-alpha concentrations were reduced in the SB239063-treatment groups. In vitro vasoreactivity studies demonstrated a significant preservation of endothelium-dependent relaxation in animals treated with the p38 MAPK inhibitor without effects on contraction or NO-mediated vasorelaxation. Proteinuria and the incidence of stroke (53% versus 7%) were also reduced significantly in the SB239063-treated groups. CONCLUSIONS: These results demonstrate a crucial role for p38 MAPK in hypertensive cardiac hypertrophy and end-organ damage. Interrupting its function with a specific p38 MAPK inhibitor halts clinical deterioration.

Animals↗
PubMed2001

Somatostatin receptor scintigraphy in the management of cerebral malignant ectomesenchymoma: a case report.

A 10-year-old girl presented with a cerebral malignant ectomesenchymoma (MEM), a very unusual tumour with undifferentiated mesenchymal as well as ectodermal elements. Somatostatin receptor scintigraphy (SRS) was performed during the diagnostic workup. The recurrent residual tumour mass was exactly visualized with SRS, and was negative after successful treatment of the patient. The potential application of SRS in initial staging, follow-up and therapy planning in MEM is discussed. This is the first application of SRS in MEM.

Brain Neoplasms↗
PubMed2001

(99m)Tc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat model.

INTRODUCTION: In the present study, (99m)Tc-radiolabelled E-selectin binding peptide ((99m)Tc-IMP-178) was investigated for its potential to image acute pyogenic osteomyelitis in a new animal model. Intraindividual comparisons were performed using an irrelevant peptide ((99m)Tc-IMP-100) to demonstrate specificity. METHODS: An acute pyogenic osteomyelitis was induced by injecting 0.05 ml of 5% sodium morrhuate and 5x10(8) CFU of Staphylococcus aureus into the medullary cavity of the right tibia in 16 rats. Sixteen additional rats served as untreated controls. Whole-body imaging of pyogenic (n=4) and untreated (n=4) animals was performed continuously during the first 8 h (12 MBq i.v. of (99m)Tc-IMP-178 and (99m)Tc-IMP-100 for control), and one further single image was acquired after 16 h p.i. Tissue biodistribution studies were performed in 12 rats with an acute pyogenic osteomyelitis and in 12 untreated rats 1, 4 and 24 h after injection. Data of the histological/radiological and haematological investigations were obtained in all animals. RESULTS: Histopathologically, 15 of 16 treated rats (93%) developed an acute pyogenic osteomyelitis showing a major infiltration of the bone marrow by polymorphonuclear leukocytes as well as the formation of sequestra. Haematologically, the number of leukocytes increased by 100%, the lymphocytes by 11% and the granulocytes decreased by 39%. After i.v. injection, (99m)Tc-IMP-178 rapidly cleared from the body resulting in good scintigraphic target-to-background (T/B) ratios. The highest uptake of the tracer in the pyogenic bone was observed at 60 min p.i. (0.43+/-0.02% ID.g-1 for (99m)Tc-IMP-178 and 0.30+/-0.02% ID.g-1 for (99m)Tc-IMP-100), resulting in a higher osteomyelitis-to-healthy collateral ratio with T/B of 2.40+/-0.65 ((99m)Tc-IMP-178) compared with 1.85+/-0.48 ((99m)Tc-IMP-100). No adverse reactions were seen after injection of (99m)Tc-IMP-178. CONCLUSIONS: (99m)Tc-IMP-178 allows imaging of an acute osteomyelitic lesions, presumably by interaction of (99m)Tc-IMP-178 with activated upregulated vascular endothelium.

Acute Disease↗
PubMed2001

Imaging tumors with peptide-based radioligands.

Regulatory peptides are small, readily diffusable and potent natural substances with a wide spectrum of receptor-mediated actions in humans. High affinity receptors for these peptides are (over-) expressed in many neoplasms, and these receptors may represent, therefore, new molecular targets for cancer diagnosis and therapy. This review aims to give an overview of the peptide-based radiopharmaceuticals which are presently already commercially available or which are in advanced stages of their clinical testing so that their broader availability is anticipated soon. Physiologically, these peptides bind to and act through G protein-coupled receptors in the cell membrane. Historically, somatostatin analogs are the first class of receptor binding peptides having gained clinical application. 111In-DTPA-[D-Phe1]-octreotide is the first and only radiopeptide which has obtained regulatory approval in Europe and the United States to date. Extensive clinical studies involving several thousands of patients have shown that the major clinical application of somatostatin receptor scintigraphy is the detection and the staging of gastroenteropancreatic neuroendocrine tumors (carcinoids). In these tumors, octreotide scintigraphy is superior to any other staging method. However, its sensitivity and accuracy in other, more frequent neoplasms is limited. Radiolabeled vasoactive intestinal peptide (VIP) has been shown to visualize the majority of gastrointestinal adenocarcinomas, as well as some neuroendocrine tumors, including insulinomas (the latter being often missed by somatostatin receptor scintigraphy). Due to the outstanding diagnostic accuracy of the pentagastrin test in detecting the presence, persistence, or recurrence of medullary thyroid cancer (MTC), we postulated the expression of the corresponding (ie. cholecystokinin [CCK-] -B) receptor type in human MTC. This receptor is also widely expressed on human small-cell lung cancer. Indeed, 111In-labeled DTPA derivatives of gastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and patients. A variety of further peptide-based radioligands, e.g. among many others, gastrin-releasing peptide/bombesin, neurotensin, substance-P, pan-somatostatin (somatostatin derivatives which bind to all five receptor subtypes) or glucagon-like peptide-1 (glp-1) analogs (the latter for the specific detection of insulinomas), is currently under development. Summarizing, radiolabeled regulatory peptides have opened new horizons in nuclear oncology for diagnosis (and potential internal radionuclide therapy). Future work will probably reveal a multitude of novel potentially clinically useful peptide-based radioligands.

Humans↗