[Show abstract][Hide abstract] ABSTRACT: The ability of integrated (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to distinguish between benign and malignant incidental non-secreting adrenal masses was evaluated in cancer patients. Results were compared with those of CT and shift magnetic resonance imaging (MRI). A total of 1832 cancer patients who had undergone FDG PET/CT scans were retrospectively evaluated. Visual interpretation, tumour maximum standardized uptake value (SUV(max)), liver SUV(max) and tumour/liver SUV(max) ratios were correlated with the findings of CT, shift MRI and final diagnosis (based on biopsy or clinical/radiological follow-up). A total of 109 adrenal masses were found: 49 were malignant and 60 were benign on final diagnosis. A tumour/liver SUV(max) ratio threshold of 1.0 was more accurate in differentiating the tumour type than tumour SUV(max) or visual interpretation alone. Diagnostic accuracy of CT and shift MRI (92 - 97%) was similar to that for FDG PET/CT (94 - 97%). In conclusion, FDG PET/CT accurately characterizes adrenal tumours, with excellent sensitivity and specificity. Use of 1.0 as the threshold for the tumour/liver SUV(max) ratio seems to be promising for distinguishing benign from malignant adrenal masses in cancer patients.
The Journal of international medical research 04/2010; 38(2):633-44. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Salivary gland dysfunction with xerostomia is a major clinical problem without a causal therapy in most cases. The development of an animal model for scintigraphic assessment of salivary gland function has great clinical relevance for the investigation of promising new diagnostic and therapeutic strategies for chronic salivary gland diseases. This study reports the first experiences with scintigraphic analyses of salivary gland function in a rat model.
Anatomical and scintigraphic studies were performed for topographic differentiation of major salivary glands of Wistar rats. (⁹⁹m)technetium pertechnetate salivary gland scanning was performed, appropriate regions of interest were determined and the gland-to-background ratio was examined for the evaluation of salivary gland function.
The quantitative analysis of salivary gland scintigraphy revealed a reliable comparison of major salivary glands on both sides with the gland-to-background ratio ranging from 1.26 to 1.94 with an average of 1.51.
This model seems to be appropriate for functional studies in an experimental setting.
In vivo (Athens, Greece) 01/2010; 24(5):681-5. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nuclear medicine imaging is now well accepted for the localization of septic foci. But in patients the results of infection scintigraphy, radiology and ultrasound remain unsatisfactory in the diagnosis of fever of unknown origin (FUO). In contrast to septic infections, patients with FUO - mostly in elderly patients - tend to have such conditions as occult tumours, atypical pneumonia, hematoblastosis, malignant lymphomas. (18)F(Fluor-18)-Fluordeoxyglucose-PET ((18)F-FDG PET) has made it possible to localize symptomatically occult changes with a high diagnostic accuracy and to achieve differentiation between benign and malignant changes.
[Show abstract][Hide abstract] ABSTRACT: This study describes the physicobiological characterization of PEI- and PEG-PEI polyplexes containing partially 2'-OMe modified 25/27mer dicer substrate siRNAs (DsiRNAs) and their in vivo behavior regarding biodistribution and systemic bioavailability after pulmonary application as well as their ability to knock down gene expression in the lung. Biophysical characterization included circular dichroism of siRNA in polyplexes, condensation efficiency of polymers and in vitro stability. After in vivo application, biodistribution and kinetics of radiolabeled polyplexes were quantified and recorded over time in three-dimensional SPECT images and by end point scintillation counting. The influence on lung tissue and on the humoral and cellular immunosystem was investigated, and finally knockdown of endogenous gene expression in the lung was determined qualitatively. While all of the polymers used in our study were proven to effectively condense siRNA, stability of the complexes depended on the PEG grafting degree. Interestingly, PEI 25 kDa, which showed the least interaction with mucin or surfactant in vitro, performed poorly in vivo. Our nuclear imaging approach enabled us to follow biodistribution of the instilled nanocarriers over time and indicated that PEGylated nanocarriers are more suitable for lung application. While moderate proinflammatory effects were attributed to PEI25k-PEG(2k)(10) nanocarriers, none of the treatments caused histological abnormalities. Our preliminary in vivo knockdown experiment suggests that PEG-PEI/siRNA complexes are promising nanomedicines for pulmonary siRNA delivery. These results encouraged us to further investigate possible adverse effects and to quantify in vivo gene silencing in the lung after intratracheal instillation of PEG-PEI/siRNA complexes.
[Show abstract][Hide abstract] ABSTRACT: ReO(4)(-) has similar kinetics regarding the sodium iodide symporter (NIS) to I(-) and TcO(4)(-) in NIS-expressing tissue. We investigated the therapeutic potential of (186)ReO(4)(-) in NIS-transfected neuroendocrine tumour tissue.
For experiments, the stably NIS-transfected pancreatic neuroendocrine cancer cell line Bon1C was used. NIS-mediated internalization and externalization experiments in vitro and a biodistribution study in nude mice bearing Bon1C xenografts were performed. A therapy study was also conducted consecutively in nude mice xenografted with Bon1C in which the mice were injected intravenously with Na(186)ReO(4).
In vitro studies showed exponential internalization and efflux kinetics of (186)ReO(4)(-) in the cell line. The biodistribution study showed high uptake of (186)ReO(4)(-) in NIS-expressing tumours. Tumour growth inhibition was significant after injection of (186)ReO(4) in two groups of animals treated with activity levels below the determined maximum tolerable activity as compared to controls.
These results indicate that the use of (186)ReO(4)(-) in the treatment of NIS-expressing neuroendocrine tumours is feasible and support the concept of using NIS as a therapeutic target for (186)ReO(4)(-).
European Journal of Nuclear Medicine 06/2009; 36(11):1767-73. · 4.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The diagnostic accuracy of infection scintigraphy with (99m)Tc-labelled monoclonal antibody Fab' fragments (sulesomab) was studied in patients with suspected total knee arthroplasty (TKA) infection. Images from 26 patients were evaluated by two independent readers and compared with a quantitative interpretation of time-activity courses. Microbiological examinations and joint aspiration results were used as reference standards. Histologically, aseptic TKA loosening occurred in two patients and severe, moderate or mild septic loosening in four, nine and 11 patients, respectively. Diagnostic accuracy for severe infection was 100% for both readers, whereas for moderate infection accuracy decreased by 12% and 12% for readers one and two, respectively. For mild infection a further decrease of approximately 61% and 52% occurred for readers one and two, respectively. Quantitative evaluation gave significantly better results over visual interpretation with a diagnostic accuracy of 100% for severe infection and decreased by only 10% and 15% in patients with moderate and mild infection, respectively. Quantitative evaluation of (99m)Tc-Fab' fragments is highly sensitive and specific for diagnostic imaging of infection in patients with septically-loosened TKA.
The Journal of international medical research 02/2009; 37(1):54-67. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal neuroendocrine tumors (NET) are mostly malignant tumors with a low incidence of 0.002–0.76 per 100,000 people
per year. They are less malignant than adenocarcinomas of the gastrointestinal tract, most of them are highly differentiated,
and they show slow growing patterns. Therefore, the term “carcinoid” was introduced by Oberndorfer in 1907 to distinguish
this tumor entity from the more aggressive adenocarcinomas. Nowadays, to avoid confusion in the terminology, the nomenclature
of NET should follow the WHO classification (Solcia et al., 2000). Older classifications, such as the well-known one from Williams and Sandler (1963) include tumors with different
clinical and pathological features in the same group (such as ”foregut”) and, therefore, should not be used.
[Show abstract][Hide abstract] ABSTRACT: HintergrundZiel der vorliegenden Studie war die Bewertung der diagnostischen Treffsicherheit nuklearmedizinischer Untersuchungstechniken
bei Patienten mit schmerzhafter Knieprothese.
Material und MethodenZwischen 2003 und 2007 wurden 87 Patienten mit schmerzhafter Knieprothese sowohl mit der 99mTc-Dreiphasenskelettszintigraphie (99mTc-Dreiphasen-DPD; n=120) als auch mit 99mTc-anti-Granulozyten-Antikörpern (Behring-Werke 250/183; n=20) untersucht.
ErgebnisseAusgewertet wurden 87 Patienten mit 94 Knieprothesen mit Verdacht auf septische Prothesenlockerung. Sensitivität, Spezifität,
positiver und negativer prädiktiver Wert sowie die diagnostische Genauigkeit mit der 99mTc-Dreiphasen-DPD zur Unterscheidung zwischen septischer und aseptischer Knieprothesenlockerung betrugen 100, 85, 55, 100,
73 und bei BW 250/183 91, 66, 76, 85, 80%. Ein signifikanter Zugewinn an diagnostischer Genauigkeit mit entsprechend 94, 88,
89, 95 und 89% (p <0,001) konnte erreicht werden, wenn beide Methoden kombiniert ausgewertet wurden.
SchlussfolgerungBeide Methoden alleine haben einen hohen negativen prädiktiven Aussagewert, aber die Kombination beider Methoden ergänzen
sich, sodass ein signifikanter Zugewinn an diagnostischer Genauigkeit und positivem prädiktivem Aussagewert zum spezifischen
Nachweis einer Knieprothesenlockerung erreicht werden kann.
RationaleThe aim of the present study was to calculate the overall diagnostic accuracy of nuclear medical imaging in patients with
painful knee arthroplasty.
Material and methodsThis retrospective study of all patients (n=87) where a 99mTc-triple phase bone scintigraphy (TPBS; n=120) and 99mTc-anti-granulocyte scintigraphy (BW 250/183; n=20) for a painful knee arthroplasty was performed between 2003 and 2007.
ResultsA total of 87 patients with 94 knee arthroplasties were examined to detect septic and aseptic loosening and to differentiate
between them. The sensitivity, specificity, the positive and negative predictive value and accuracy of TPBS for the detection
of septic knee arthroplasty loosening was 100%, 85%, 55%, 100%, 73% and for BW 250/183 was 91%, 66%, 76%, 85%, 80% for sepsis,
respectively. A significant increase in diagnostic accuracy with 94%, 88%, 89%, 95% und 89% (p <0.001) could be achieved when
both methods were used in combination.
ConclusionBoth methods alone have high negative predictive values, but the combination of both is complementary and significantly increases
the diagnostic accuracy and positive predictive value for final diagnosis of knee arthroplasty loosening.
Der Radiologe 12/2008; 49(1):59-67. · 0.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 99mTc-tetrofosmin single photon emission computed tomography (SPECT) is routinely used in the evaluation of coronary artery disease. A variety of different tumors, however, also demonstrate 99mTc-tetrofosmin uptake. We report six patients found with unexpected mediastinal and thoracic tumor uptake during Tc-tetrofosmin myocardial perfusion scintigraphy (MPS).
We investigated 2,155 patients with Tc-tetrofosmin MPS during 2006-2007. One thousand four hundred and eighty-six of these patients had no coronary history and were sent to our department due to newly developed thoracic complaint such as chest pain, dyspnea and others. Six hundred and sixty-nine patients had coronary history. All patients underwent 99mTc-tetrofosmin exercise study. Patients with unexpected extracardiac Tc-tetrofosmin findings during MPS were referred to PET/CT for further diagnostic investigation. Region of interest (ROI; 99mTc-tetrofosmin) and SUVmax (2-[F]fluoro-2-deoxy-D-glucose, F-FDG) were estimated and the results were compared with histological findings.
Abnormal mediastinal and/or thoracic activities were visualized in six of the 2,155 patients with 99mTc-tetrofosmin images. Subsequently, the patients underwent resection of a thymoma (n=2), nonsmall cell lung cancer (n=1) and breast cancer (n=3). In the patients with breast cancer one was a male patient with ductal, invasive breast cancer. Benign thymomas showed high 99mTc-tetrofosmin ROI >4.0 and low F-FDG SUVmax <2.0, whereas low 99mTc-tetrofosmin ROI <2.0 were found in nonsmall cell lung cancer and breast cancer and high F-FDG SUVmax >2.5 in these malignant tumors.
During Tc-tetrofosmin SPECT exercise stress tests performed in patients with suspected coronary artery disease, much more attention must be given to unexpected extracardiac uptakes. With 99mTc-tetrofosmin a large variety of different unknown tumors can be detected during MPS.
Nuclear Medicine Communications 11/2008; 29(11):963-9. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Active as well as passive immunization against beta-amlyoid (Abeta) has been proposed as a treatment to lower cerebral amyloid burden and stabilize cognitive decline in Alzheimer's disease (AD). To clarify the mechanism of action underlying passive immunization, the in vivo distribution (and sites of degradation) of peripherally administered radiolabeled human and mouse anti-Abeta antibodies were analyzed in a transgenic mouse model of AD. In APP23 mice, a model in which mutated human amyloid precursor protein is overexpressed, the biodistribution of intravenously applicated (111)indium-conjugated affinity-purified human polyclonal autoantibodies (NAbs-Abeta) was compared to that of monoclonal anti-Abeta(1-17) (6E10), anti-Abeta(17-24) antibodies (4G8) and anti-CD-20 (Rituximab), a non-Abeta targeting control. Blood clearance half-lives were 50+/-6h for Rituximab, 20-30h for NAbs-Abeta, 29+/-5h for 4G8 and 27+/-3h for 6E10. Blood activity was higher for 6E10 at 4h as compared to 4G8, Rituximab and NAbs-Abeta. At the 96h time point, Rituximab had the highest blood activity among the antibodies tested. As expected, all antibodies displayed hepatobiliary clearance. Additionally, NAbs-Abeta was excreted in the urinary tract. Liver and kidney uptake of NAbs-Abeta increased over time and was higher than in the monoclonal antibodies at 48h/96h. The brain-to-blood radioactivity ratio for NAbs-Abeta at later time points (>48h) was higher than that of 6E10, 4G8 and Rituximab. In addition, the distribution varied, with highest values found in the hippocampus. Our data indicate a cerebral accumulation of human NAbs-Abeta in the APP23 model. Further studies with human immunoglobulins and particularly with those that recognize different Abeta-epitopes are required in order to delineate in more detail the mode of action of NAbs-Abeta.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to calculate the overall diagnostic accuracy of nuclear medical imaging in patients with painful knee arthroplasty.
This retrospective study of all patients (n=87) where a (99m)Tc-triple phase bone scintigraphy (TPBS; n=120) and (99m)Tc-anti-granulocyte scintigraphy (BW 250/183; n=20) for a painful knee arthroplasty was performed between 2003 and 2007.
A total of 87 patients with 94 knee arthroplasties were examined to detect septic and aseptic loosening and to differentiate between them. The sensitivity, specificity, the positive and negative predictive value and accuracy of TPBS for the detection of septic knee arthroplasty loosening was 100%, 85%, 55%, 100%, 73% and for BW 250/183 was 91%, 66%, 76%, 85%, 80% for sepsis, respectively. A significant increase in diagnostic accuracy with 94%, 88%, 89%, 95% und 89% (p <0.001) could be achieved when both methods were used in combination.
Both methods alone have high negative predictive values, but the combination of both is complementary and significantly increases the diagnostic accuracy and positive predictive value for final diagnosis of knee arthroplasty loosening.
Der Radiologe 08/2008; 49(1):59-67. · 0.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the diagnostic value of fine-needle aspiration cytology (FNAC) before thyroidectomy in an endemic goiter region.
One hundred patients with preoperative FNAC of thyroid nodules who underwent thyroidectomy were recruited. FNAC were classified into five groups. 0, no thyroid cells; 1, normal thyroid cells; 2, degenerative thyroid cells without evidence of malignacy; 3, follicular or oncocytary neoplasia; and 4, malignant thyroid cells. FNAC was compared with postoperative histopathological diagnoses.
Only 76% of the FNAC allowed an adequate cytological examination. In 15 patients (15%), carcinomas were found in the postoperative histopathological diagnosis (including four follicular carcinomas). In the 48 patients of FNAC groups 3 and 4, nine carcinomas (18.7%) were found (including four follicular carcinomas). In the 28 patients of groups 1 and 2, there was only one papillary carcinoma (3.5%). In the 24 patients of group 0, there were two papillary, two follicular, and one anaplastic carcinomas (total of 20.8%). The sensitivity, specificity, and likelihood ratio (LR) of the FNAC for benign nodules were 90%, 40.9%, 0.24, respectively. The LR for malignant nodules was 13.2, and that for follicular neoplasia was 0.55.
Despite the high prevalence of carcinoma in an endemic goiter region, FNAC disappointed its diagnostic expectation. The lower specificity of FNAC may be caused by a higher prevalence of thyroid nodules in an endemic goiter region or by the absence of a specialized cytopathologist.
[Show abstract][Hide abstract] ABSTRACT: The differentiation of septic and aseptic total knee arthroplasty (TKA) loosening often generates major difficulties. Nuclear medicine imaging of infection has proven to have a high potential. Therefore, we evaluated the diagnostic accuracy of 99m Tc-DPD triple-phase bone scintigraphy (TPBS) in combination with 99mTc-labelled antigranulocyte antibody (BW 250/183) for the differentiation of septic and aseptic TKA loosening. Eighty seven patients with 94 TKA were investigated between 2003 and 2007. TPBS was classified as abnormal when an increased blood supply and increased bone uptake around the TKA was visible. BW 250/183 was considered positive for infection, when the activity around the TKA increased from 4 hr to 24 hr by more than 10% as compared with normal bone marrow images after injection of the radioabelled monoclonal anti- granulocyte antibody. TPBS was true positive for septic and aseptic loosening in all patients, whereas false positive results for septic loosening were found in 9/20 cases (n=45%). False positive results with TPBS were correctly diagnosed by a negative BW 250/183 scan. These results suggest that TPBS is highly sensitive for the diagnosis of TKA loosening, whereas BW 250/183 allows for a specific diagnosis of periprosthetic infection. The combination of both is complementary and increases in diagnostic accuracy significantly (p
The Open Medical Imaging Journal. 01/2008; 2(1):24-31.
[Show abstract][Hide abstract] ABSTRACT: Single photon emission computed tomography (SPECT) using [(123)I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinson's disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [(123)I]FP-CIT binding indeed correlates with the striatal dopamine transporter protein level. It is unclear, however, if there is a stable relationship between the striatal [(123)I]FP-CIT binding and other functionally important parameters of the nigrostriatal system, such as the striatal dopamine levels and the number of dopaminergic neurons in the substantia nigra. To assess this question experimentally, we studied two different mouse models of PD, namely a mild 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication paradigm, to model mild nigrostriatal damage and the intrastriatal 6-hydroxydopamine paradigm to model more advanced nigrostriatal damage. Our data demonstrate that the striatal [(123)I]FP-CIT binding measured by SPECT in vivo precisely predicts the striatal dopamine concentrations, but does not necessarily correlate with the nigral dopaminergic cell number. Thus, the present work underscores that FP-CIT SPECT does only allow judging the integrity of the striatal dopaminergic nerve terminals, but not the nigral dopaminergic cells in PD. This finding may have significant impact on the use of [(123)I]FP-CIT SPECT as a surrogate marker for clinical trials aimed at measuring neuroprotection.
[Show abstract][Hide abstract] ABSTRACT: There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of radioisotope therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects.
Biodistribution studies and in vivo therapy experiments were performed in nude mice carrying stably NIS-expressing neuroendocrine tumor xenografts following i.v. injection of (131)I and (99m)Tc pertechnetate. To show the usefulness of NIS as an imaging reporter gene, (99m)Tc pertechnetate uptake was imaged in vivo using a clinical gamma camera in combination with a custom-made single pinhole collimator, followed by SPECT/small animal MRI data coregistration.
NIS-expressing neuroendocrine tumors strongly accumulated (131)I and (99m)Tc pertechnetate, as did thyroid, stomach, and salivary gland. The volume of NIS-expressing neuroendocrine tumors decreased significantly after therapeutic administration of (131)I or (99m)Tc pertechnetate, whereas control tumors continued to grow. NIS-mediated uptake of (99m)Tc pertechnetate could be imaged in vivo at high resolution with a clinical gamma camera equipped with a custom-made single pinhole collimator. High-resolution functional and morphologic information could be combined in a single three-dimensional data set by coregistration of SPECT and small animal MRI data. Lastly, we demonstrated a therapeutic effect of (99m)Tc pertechnetate on NIS-expressing neuroendocrine tumors in cell culture and, for the first time, in vivo, thought to be due to emitted Auger and conversion electrons.
NIS-expressing neuroendocrine tumors efficiently concentrate radioisotopes, allowing for in vivo high-resolution small animal SPECT imaging as well as rendering possible successful radioisotope therapy of neuroendocrine tumors.
European journal of nuclear medicine and molecular imaging 06/2007; 34(5):638-50. · 5.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Somatostatin receptor scintigraphy (SRS) is a valuable method for the detection of somatostatin receptor-positive lesions. Most gastrinomas (over-)express the somatostatin receptor subtype 2 which can be targeted by In-111 labeled Octreotide. Different studies show a high sensitivity of SRS for the localization and staging of gastrinomas. SRS seems to be superior to other non-invasive imaging modalities and has been proven to significantly contribute to patient management. However, the sensitivity depends on the size and exact localization of the tumors. Smaller lesions and lesions located in the duodenum show a significantly lower sensitivity. In any case, SRS belongs to the routine imaging procedure for gastrinomas for localization and staging and can also be used for evaluation of the tumor progression.
Wiener klinische Wochenschrift 02/2007; 119(19-20):593-6. · 0.81 Impact Factor