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Aims: Nuclear imaging may have an increasing role in the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to compare prospectively the Gallium-67 citrate ((67)Ga) scintigraphy results with those obtained by positron emission tomography (PET) using (11)C-acetate in patients with HCC., Methods: We prospectively analysed 21 patients (mean age, 64+/-11 years) with histopathologically verified HCC undergoing (11)C-acetate PET and (67)Ga scintigraphy. (67)Ga scans were not performed in three of these 21 patients due to the exacerbation of the disease. Whole-body (11)C-acetate PET were performed following intravenous injection of 850 MBq of (11)C-acetate. For (67)Ga scintigraphy, whole-body, planar and single photon emission computed tomography imaging acquisitions were performed after intravenous application of a mean dose of 189 MBq (67)Ga., Results: (67)Ga scintigraphy found abnormalities only in 10 of 18 patients (56%) and detected 22 of 46 clinically involved sites (48%); it was false-positive in two patients. (11)C-acetate PET found abnormalities in 14 of 18 patients (78%) and detected 36 of 46 clinical lesions (78%); it was false-positive in one patients. In one patient with left supraclavicular lymph node metastases, neither the (67)Ga scintigraphy nor the conventional computed tomography have shown the lesions, which were clearly demonstrated by the (11)C-acetate PET., Conclusion: Our results indicate significantly higher sensitivity and specificity of (11)C-acetate PET than (67)Ga scan in detection of HCC lesions. This study suggests that imaging with (11)C-acetate PET might play a potential role in the diagnostic workup of patients with HCC.

This work describes a microdosing study with an investigational, carbon 11-labeled antiamyloid drug, 1,1'-methylene-di-(2-naphthol) (ST1859), and positron emission tomography (PET) in healthy volunteers (n = 3) and patients with Alzheimer's disease (n = 6). The study aimed to assess the distribution and local tissue pharmacokinetics of the study drug in its target organ, the human brain. Before PET studies were performed in humans, the toxicologic characteristics of ST1859 were investigated by an extended single-dose toxicity study according to guidelines of the Food and Drug Administration and European Medicines Agency, which are relevant for clinical trials with a single microdose. After intravenous bolus injection of 341 +/- 21 MBq [(11)C]ST1859 (containing <11.4 nmol of unlabeled ST1859), peripheral metabolism was rapid, with less than 20% of total plasma radioactivity being in the form of unchanged parent drug at 10 minutes after administration. In both the control and patient groups, uptake of radioactivity into the brain was relatively fast (time to reach maximum concentration, 9-17 minutes) and pronounced (maximum concentration [standardized uptake value], 1.3-2.2). In both healthy volunteers and patients, there was a rather uniform distribution of radioactivity in the brain, including both amyloid-beta-rich and -poor regions, with slow washout of radioactivity (half-life, 82-185 minutes). In conclusion, these data provide important information on the blood-brain barrier penetration and metabolism of an investigational antiamyloid drug and suggest that the PET microdosing approach is a useful method to describe the target-organ pharmacokinetics of radiolabeled drugs in humans.

Purpose: 11beta-Hydroxylase is a key enzyme in the biosynthesis of adrenocortical steroid hormones and is a suitable target for the imaging of the adrenal cortex. [(11)C]Metomidate (MTO), [(11)C]etomidate (ETO) and desethyl-[(18)F]fluoroethyl-etomidate (FETO) are potent inhibitors of this enzyme and are used for PET imaging of adrenocortical pathologies. The aims of this study were (1) to evaluate and compare the metabolic stability of MTO, ETO and FETO against esterases and (2) to investigate the metabolic pattern of FETO in vivo., Methods: In vitro assays were performed using different concentrations of MTO, ETO and FETO with constant concentrations of carboxylesterase. Human in vivo studies were performed with human blood samples drawn from the cubital vein. After sample clean-up, the serum was analysed by HPLC methods., Results: In vitro assays showed Michaelis-Menten constants of 115.1 mumol for FETO, 162.0 mumol for MTO and 168.6 mumol for ETO. Limiting velocities were 1.54 mumol/min (FETO), 1.47 mumol/min (MTO) and 1.35 mumol/min (ETO). This implies insignificantly decreased esterase stability of FETO compared with MTO and ETO. In vivo investigations showed a rapid metabolisation of FETO within the first 10 min (2 min: 91.41%+/-6.44%, n=6; 10 min: 23.78%+/-5.54%, n=4) followed by a smooth decrease in FETO from 20 to 90 min (20 min: 11.23%+/-3.79% n=4; 90 min: 3.68%+/-3.65%, n=4). Recovery rate was 61.43%+/-3.19% (n=12)., Conclusion: In vitro experiments demonstrated that FETO stability against esterases is comparable to that of ETO and MTO. The metabolic profile showed that FETO kinetics in humans are fast.

Purpose: To assess the clinical value of computed tomography (CT) and magnetic resonance imaging (MRI) image fusion with 11C-acetate (AC) positron emission tomography (PET) imaging for detection and exact location of clinically occult recurrences., Patients and Methods: Fifty prostate cancer patients with elevated/increasing serum prostate-specific antigen levels after radical therapy underwent whole-body AC PET. Uptake was initially interpreted as normal, abnormal, or equivocal. In case of abnormal or equivocal uptake, additional conventional imaging techniques, such as CT, MRI, and bone scans, were performed. To precisely define the anatomic location of abnormal uptake and to improve characterization of equivocal lesions, a software-assisted image fusion (CT-PET, MRI-PET) was performed and evaluated as site-by-site analysis of 51 abnormal (n = 37) or equivocal (n = 14) sites of all 50 patients. In 17 patients, additional histopathologic evaluation was available., Results: In five (10%), 13 (26%), and 32 (64%) of the 50 patients, AC PET studies demonstrated AC uptake judged as normal, equivocal, and abnormal, respectively. Image fusion changed characterization of equivocal lesions as normal in five (10%) of 51 sites and abnormal in nine (18%) of 51 sites. It precisely defined the anatomic location of abnormal uptake in 37 (73%) of 51 sites. AC PET findings did influence patient management in 14 (28%) of 50 patients., Conclusion: Retrospective fusion of AC PET and CT/MRI is feasible and seems to be essential for final diagnosis. This is particularly true in patients with AC uptake in the prostate region.

Purpose: Functional imaging of the adrenal cortex by means of PET may play an important clinical role. Recently, we presented the synthesis and first evaluation of a novel 11beta-hydroxylase inhibitor, [(18)F]FETO, in rats displaying high tracer accumulation in the adrenals. In this study, we aimed to investigate for the first time the potency of [(18)F]FETO as a PET tracer for the adrenal cortex in humans., Methods: An average preparation yielded 1-2 GBq of [(18)F]FETO ready to use. Ten healthy volunteers aged 24-57 years (five male and five female) were included in the study. After i.v. administration of 365 MBq [(18)F]FETO (246-391 MBq), dynamic images were acquired in 2D standard mode in 14 frames over 45 min. Afterwards, whole-body scanning was performed. In addition to visual interpretation, semi-quantitative analysis using standardised uptake values (SUVs) was conducted., Results: [(18)F]FETO distribution was similar in all scanned volunteers. Visually, pronounced accumulation of [(18)F]FETO was found in the adrenals, whereas moderate uptake was observed-at least in some of the subjects-for liver, renal calices, gallbladder, stomach walls and pancreas. Kidney and bowels showed only faint uptake. Median SUVs for the right and left adrenal glands were 15.6 (10.0-28.6) and 15.7 (10.3-35.9), respectively. The reference tissue (liver) displayed a median SUV of 2.5 (2.2-4.6)., Conclusion: [(18)F]FETO is a valuable tracer for adrenocortical PET imaging, combining the longer half-life of( 18)F with a high 11beta-hydroxylase selectivity. In accordance with our findings in rats, FETO PET revealed very high accumulation in the adrenal glands in healthy volunteers.

Purpose: Although polyphosphonates (PPs) were introduced as bone imaging agents in nuclear medicine in the early 1970s, the mechanisms involved in their uptake still remain unclear. Suggested mechanisms range from mineral adsorption with disputed binding to the organic phase, over incorporation into the mineralisation process to a combination of both mechanisms. Thus, our investigations aimed to: (1) evaluate adsorption parameters of (99m)Tc-MDP, (153)Sm-EDTMP and (18)F-fluoride on mineralising osteoblast cultures, (2) correlate the radiotracer binding measured in the cell cultures with binding values from our previously presented mineral model and (3) compare binding with cell number., Methods: Primary osteoblasts were obtained by sequential digestion of foetal mice calvariae. The cells were incubated with 0.3 mumol of radiolabelled PPs or 25 MBq (18)F-fluoride for 120 min. Gamma signals from labelled samples were detected with a Millennium Hawkeye SPECT camera or with a dedicated Advance full-ring PET scanner and the binding percentages were calculated., Results: From days 8 to 15 of culture, the percent binding of all evaluated tracers increased significantly, whereas the protein concentration showed insignificant changes. Additional comparisons of the binding values with our recently published pre-vivo model revealed remarkable agreement, suggesting solely bone-forming minerals to be responsible for radiotracer binding., Conclusion: This study provides evidence that binding of the evaluated radiotracers is not associated with osteoblast numbers but only with the concentration of bone-forming minerals. The presented correlations substantiate our recently presented pre-vivo model for the evaluation of bone-seekers: mechanisms associated with the uptake of bone-seekers are irreversible and mineral-associated processes.

Nucleophilic aromatic substitution is a challenging task in radiochemistry. Therefore, a thorough evaluation and optimisation of this step is needed to provide a satisfactory tool for the routine preparation of [(18)F]fluorinated aromatic amino acids. Two methods, already proposed elsewhere, were evaluated and improved. The yields for the radiofluorination were increased whereas activity loss during solid phase extraction was observed. Radiochemical yields for the two methods were 92.7+/-5.5% (method 1) and 92.1+/-12.3% (method 2) for conversion and 11.1+/-2.8% (method 1) and 34.8+/-0.6% (method 2) for purification, respectively. In total, we demonstrate an optimised method for the preparation of this important class of [(18)F]fluorinated synthons for PET.

The present study focused on the preparation of novel bone tracers containing yttrium as radionuclide or carrier. Moreover, these preparations were comparatively evaluated in vitro on the basis of a recently presented pre vivo model comprising binding studies on synthetic and human bone powder. It was shown that among the therapeutic radionuclides, no carrier added [(90)Y]-EDTMP exceeded [(188)Re]-EDTMP while yielding lower binding values than [(153)Sm]-EDTMP. Furthermore, the authors investigated the influence of "foreign" carriers added to [(90)Y]-EDTMP, [(99m)Tc]-EDTMP and [(111)In]-EDTMP by the method of cross-complexation. The findings reveal a new paradigm: a carrier more foreign to the complexed radionuclide causes a higher binding increase on human bone matrices in vitro than a more "related" carrier.

The upgrade of a gamma camera from a 5/8" to a 1" thick crystal, the latter with StarBrite technology, prompted to the investigation of changes in performance parameters for planar scintigraphy and SPECT as well as for PET in coincidence mode. For planar and SPECT parameters, the performance was measured according to NEMA Standard Protocol NU1-2001. No changes were found in terms of intrinsic uniformity, intrinsic spatial resolution, linearity, energy resolution, system resolution, and tomographic system resolution. The only change was an increase of system sensitivity for higher energy gamma rays. For the PET scanner in coincidence mode, the image quality of the camera was determined according to NEMA NU2-2001. Visually and in terms of contrast values there was a significant improvement of image quality. Changes in image quality relevant for clinical use were tested by evaluation of planar patient scans acquired within a short time with two gamma cameras of the same type, different only in crystal thickness (5/8" and 1"). No statistically significant difference was found between corresponding scans. For planar and SPECT imaging, the gamma camera with 1" thick detector and StarBrite technology demonstrated the same performance of a camera with a 5/8" crystal. For PET in coincidence mode the new detector proved clearly superior.

The measurement of basal serum calcitonin (CT) in patients with evidence of Hashimoto's thyroiditis (HT) has been proposed in a recent study demonstrating an increased prevalence of elevated basal and stimulated CT. The aim of this study was to evaluate the frequency and relevance of elevated CT levels in HT. The basal sera CT were measured in 568 consecutive HT patients using a chemiluminescent immuno-assay. Whenever the serum CT was > 10 pg/ml, a pentagastrin (PG) stimulation test was performed. Two patients with abnormal/pathological PG tests were identified. Total thyroidectomy and lymph node dissection revealed for the first patient medullary thyroid carcinoma (MTC) and for the second patient C cell hyperplasia (CCH), together with papillary thyroid carcinoma. Our data showed a low prevalence of MTC and its premalignant condition CCH in HT patients; nevertheless, the patient with MTC presented lymph node metastasis. The fact that both cases presented without evidence of nodular thyroid disease highlights the persistent diagnostic dilemma of CT screening programs.

Purpose: Radioiodine-negative thyroid cancer presents diagnostic and therapeutic difficulties, warranting the implementation of new imaging and treatment strategies. The purpose of this study was twofold. First, we investigated in vitro the binding characteristics of 111In-DOTA-lanreotide (111In-DOTA-LAN) and 111In-DOTA-D: Phe1-Tyr3-octreotide (111In-DOTA-TOC) to cells derived from differentiated thyroid cancer (DTC). Second, we evaluated the value of somatostatin receptor (SSTR) scintigraphy with these radioligands, as compared with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), for the detection of tumour lesions in DTC patients., Methods: Binding of 111In-DOTA-LAN and 111In-DOTA-TOC to cells isolated from surgically removed thyroid tissue was evaluated in vitro by performing saturation and displacement studies. Eighteen DTC patients with elevated thyroglobulin (12 radioiodine-negative, six radioiodine-positive) were investigated with 111In-DOTA-LAN, 111In-DOTA-TOC and 18F-FDG PET scans., Results: Large numbers of SSTR binding sites for 111In-DOTA-LAN and 111In-DOTA-TOC were found on the cells investigated. Both SSTR radioligands exhibited a high binding affinity for these SSTR binding sites. 111In-DOTA-LAN and 111In-DOTA-TOC scintigraphy detected 37 and 33 lesions, respectively, in 17 (94%) patients each, whereas 18F-FDG PET revealed 30 lesions in 15 (83%) patients. Uptake of both SSTR radioligands was found in several radioiodine-negative sites. No striking differences in lesion imaging by 111In-DOTA-LAN and 111In-DOTA-TOC were found. In both radioiodine-negative and radioiodine-positive patients, more lesions were SSTR-positive/18F-FDG-negative than were 18F-FDG-positive/SSTR-negative., Conclusion: Adding a SSTR scan with these radioligands to the diagnostic work-up increases the diagnostic capacity in DTC, and should be considered particularly in radioiodine-negative patients with elevated thyroglobulin levels.

Background and Objective: Single nucleotide polymorphisms in the human multidrug-resistance gene ABCB1 have been reported to be associated with altered expression and function of P-glycoprotein, an efflux transporter, expressed at the blood-brain barrier. To test whether certain ABCB1 haplotypes contribute to interindividual differences in central nervous system drug distribution, brain distribution of a model P-glycoprotein substrate, the calcium channel inhibitor verapamil, was measured by positron emission tomography (PET) in 2 groups of healthy volunteers., Methods: Ten homozygous carriers (cases) of the TTT haplotype (3435T, 1236T, and 2677T) and 10 controls homozygous for the wild-type CGC haplotype (3435C, 2677G, and 1236C) were administered a mean intravenous bolus of 412 +/- 114 MBq carbon 11-labeled verapamil containing less than 15 nmol of unlabeled verapamil. PET imaging of brain tissue and venous blood sampling were performed for 1 hour after dosing., Results: As a measure of brain penetration, the ratio of PET area under the time-radioactivity curve (AUC) to plasma AUC was calculated from time-radioactivity curves, with a mean ratio of 1.1 +/- 0.3 (SD) (95% confidence interval, 0.9-1.3) for cases and 1.1 +/- 0.2 (95% confidence interval, 0.9-1.2) for controls, respectively (P = .96). Mean brain AUC values were 31.2 +/- 3.9 and 35.7 +/- 5.7 for the TTT and CGC haplotype, respectively (P = .11). Plasma AUCs were not significantly different., Conclusion: No difference in the brain distribution of [(11)C]verapamil could be detected in healthy volunteers differing in ABCB1 haplotypes.

Objective: Cytokines produced by cytotoxic T cells or autoantibodies lead to thyroid cell damage and/or cell death in Hashimoto's thyroiditis (HT). Anti-TPO autoantibodies (TPOAb) are the most frequently represented autoantibodies in the sera of patients with HT. Data describing the quantitative correlation between TPOAb titre and cytokine pattern are missing so far. To our knowledge this is the first study systematically evaluating the correlation of possible parameters of disease activity such as changes in CD4 and CD8 T-cell cytokine production and of TPOAb titre., Methods: Twenty-four consecutive patients (aged 29-58) with verified HT under levothyroxine therapy were included in the present study. The patients were divided into two groups. Group I: 12 HT patients with a high TPOAb titre (> 1000 U/ml), group II: 12 HT patients with a low TPOAb titre (< 100 U/ml). All patients underwent intracellular cytokine detection in CD4 and CD8 T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry. Twelve healthy volunteers matched in sex and age consisted the control group (group III)., Results: T cells from patients with a high TPOAb titre (group I) had significantly higher percentages of cells producing IFN-gamma compared to healthy donors (group III). A detailed analysis of cytokine production patterns revealed that this was accompanied by an increased frequency of single IFN-gamma positive cells, i.e. cells not expressing other cytokines tested, such as IL-2, IL-4, IL-5, IL-6, IL-10, IL-13 or TNF-beta. Similarly, patients in group I also showed higher percentages of TNF-alpha positive cells than healthy donors (group III). In this case, cells expressing TNF-alpha alone as well as cells coexpressing TNF-alpha and IFN-gamma were found at significantly higher frequencies. On the other hand, cytokine production patterns of patients with a low TPOAb titre (group II) showed significant difference neither to patients of group I nor to healthy donors (group III)., Conclusion: Taken together, we were able for the first time to demonstrate that high TPOAb titre correlates with increased frequencies of T cells producing Th/Tc1 cytokines, probably responsible for thyroid cell damage and/or death in Hashimoto's thyroiditis.

Background: Measurement of myocardial blood flow (MBF) by dynamic nitrogen 13 ammonia (NH(3)) positron emission tomography (PET) uses tracer kinetic modeling to analyze time-activity curves. We compared 2 commonly used models with 2 compartments (2C) and 3 compartments (3C) for quantification of MBF and coronary flow reserve (CFR)., Methods and Results: Seventy-seven patients underwent NH(3) PET at rest and during hyperemia. Time-activity curves for blood pool and myocardial segments were obtained from short-axis images of dynamic sequences. Model fitting of the 2C and 3C models was performed to estimate regional MBF. MBF values calculated by 2C and 3C models were 0.98 +/- 0.31 mL.min(-1).g(-1) and 1.11 +/- 0.37 mL.min(-1).g(-1), respectively, at rest (P < .0001) and 2.79 +/- 1.18 mL.min(-1).g(-1) and 2.46 +/- 1.02 mL.min(-1).g(-1), respectively, during hyperemia (P < .01), resulting in a CFR of 3.02 +/- 1.31 and 2.39 +/- 1.15 (P < .0001), respectively. Significant correlation was observed between the 2 models for calculation of resting MBF (r = 0.78), hyperemic MBF (r = 0.68), and CFR (r = 0.68)., Conclusion: Measurements of MBF and CFR by 2C and 3C models are significantly related. However, quantification of MBF and CFR significantly differs between the methods. This difference needs to be considered when normal values are established or when measurements obtained with different methods need to be compared.

Aim: In advanced seminoma the management of residuals after completion of chemotherapy is controversial. Some centres routinely perform surgery for lesions > or =3 cm diameter, others recommend surgery solely if the residual fail to shrink or show even growth. This study prospectively investigates whether FDG PET can improve the prediction of viable tumour in post-chemotherapy seminoma residuals., Materials and Methods: After an expansion of a previous study population, 54 patients from eight centres with metastatic seminoma and a CT-documented mass after chemotherapy were included in the study. Six patients were excluded from evaluation because of protocol violations. After PET, the patients underwent either surgery or were followed clinically. On follow-up the lesions were considered to be non-viable when there was unequivocal shrinking, or when the lesion remained morphologically stable for at least 24 months. Any lesion growth was assumed to be malignant. PET results were compared to CT discrimination (< or > or =3 cm) of the residual masses., Results: Fifty-two PET scans were evaluable. After adequate chemotherapy, there were 74 CT-documented residual masses ranging in size from 1 to 11 cm (median, 2.2 cm). Their dignities were confirmed histologically in 13 lesions, or by follow-up CT in 61 lesions. Four of forty-seven lesions <3 cm and 11/27 lesions > or =3 cm were viable. PET was true positive in one lesion <3 cm and in 11 lesions > or =3 cm, false negative in three lesions <3 cm, and true negative in 59 lesions (43 lesions <3 cm). No PET scan was false positive. In detecting viability the sensitivity and specificity was 73% (95% CI, 44-88), and 73% (59-83), respectively, for CT (< or > or =3 cm); and 80% (51-95), and 100% (93-100), respectively, for PET (specificity, P < 0.001)., Conclusion: In post-chemotherapy seminoma residuals, a positive PET is highly predictive for the presence of viable tumour. The specificity of PET is significantly higher than that of CT when using a > or =3 cm cut-off. A negative PET scan is excellent for the exclusion of disease in lesions > or =3 cm, with a somewhat higher sensitivity than CT (n.s.). PET can contribute to the management of residual seminoma lesions, especially in terms of avoiding unnecessary additional treatment for patients with lesions > or =3 cm.

At present, most data available on PET imaging of brain tumors using amino acids are based on l-[S-methyl-11C]methionine (MET). This radiopharmaceutical accurately delineates tumor extent, sometimes even better than CT. Since MET is playing such an important role for PET, a potent preparation method for this radiotracer allowing frequent syntheses for PET routine is desirable. Therefore, a simple disposable synthesis module was conceived without HPLC purification. Using a solid supported [11C]methylation on Al2O3 leads to the simplification of the preparation requiring only filtration for separation of precursor and MET. The presented method is able to produce high purity MET in excellent yields enough to serve several consecutive patients.

In the last decade radiolabeled tropane analogs based on beta-CIT have proven indispensable for the imaging of the dopamine transporter. However, further improvements in their pharmacodynamic and pharmacokinetic features are desirable. An important improvement, yielding in higher affinity to the dopamine transporter (DAT) vs. serotonin transporter (SERT), can be achieved by a simple replacement of the carboxylic methyl ester group in beta-CIT by a fluoroethyl ester. The preparation and ex vivo evaluation of this new beta-CIT-analog ([18F]FE@CIT) is presented here. Precursor and standard were prepared from beta-CIT and analyzed by spectroscopic methods. Yields of precursor and standard preparation were 61% and 42%, respectively. [18F]FE@CIT was prepared by distillation of [18F]bromofluoroethane ([18F]BFE) and reaction with (1R-2-exo-3-exo)8-methyl-3-(4-iodo-phenyl)-8-azabicyclo[3.2.1] octane-2-carboxylic acid. After 10 min at 150 degrees C the product was purified using a C-18 SepPak. The radiosynthesis evinced radiochemical yields of >90% (based on [18F]BFE), the specific radioactivity was >416 GBq/micromol. An average 30 microAh cyclotron irradiation yielded more than 2.5 GBq [18F]FE@CIT. For the ex vivo bioevaluation, 20 male Sprague-Dawley rats were sacrificed at 5, 15, 30, 60, and 120 min after injection. Organs were removed, weighed, and counted. For autoradiographic experiments, transverse brain slices of about 100 microm were prepared. The ex vivo evaluation showed highest brain uptake in striatal regions, followed by thalamus and cerebellum. The highest striatum to cerebellum ratio was 3.73 and the highest thalamus to cerebellum ratio was 1.65. Autoradiographic images showed a good and differentiated uptake in striatal regions with a good target-to-background ratio.

Purpose: The suitability of the 18F-labelled fluoroquinolone antibiotic ciprofloxacin ([18F]ciprofloxacin) for imaging of bacterial infections with positron emission tomography (PET) was assessed in vitro and in vivo., Methods: For the in vitro experiments, suspensions of various E. coli strains were incubated with different concentrations of [18F]ciprofloxacin (0.01-5.0 microg/ml) and radioactivity retention was measured in a gamma counter. For the in vivo experiments, 725 +/- 9 MBq [18F]ciprofloxacin was injected intravenously into four patients with microbiologically proven bacterial soft tissue infections of the lower extremities and time-radioactivity curves were recorded in infected and uninfected tissue for 5 h after tracer injection., Results: Binding of [18F]ciprofloxacin to bacterial cells was rapid, non-saturable and readily reversible. Moreover, bacterial binding of the agent was similar in ciprofloxacin-resistant and ciprofloxacin-susceptible clinical isolates. These findings suggest that non-specific binding rather than specific binding to bacterial type II topoisomerase enzymes is the predominant mechanism of bacterial retention of the radiotracer. PET studies in the four patients with microbiologically proven bacterial soft tissue infections demonstrated locally increased radioactivity uptake in infected tissue, with peak ratios between infected and uninfected tissue ranging from 1.8 to 5.5. Radioactivity was not retained in infected tissue and appeared to wash out with a similar elimination half-life as in uninfected tissue, suggesting that the kinetics of [18F]ciprofloxacin in infected tissue are governed by increased blood flow and vascular permeability due to local infection rather than by a binding process., Conclusion: Taken together, our results indicate that [18F]ciprofloxacin is not suited as a bacteria-specific infection imaging agent for PET.

Unlabelled: The aim of this study was to compare nonfluoroscopic electroanatomic mapping (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of myocardial viability. In particular, we sought to elucidate differences of electromechanical properties between the perfusion/metabolism mismatch as an indicator of a potentially reversible ischemic injury and the perfusion/metabolism match indicating irreversibly damaged myocardial tissue., Methods: Twenty-one patients with coronary artery disease underwent NOGA mapping of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and resting 201Tl SPECT of myocardial perfusion., Results: Electrical activity was 10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in hypoperfused segments with maintained glucose metabolism (perfusion/metabolism mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused segments with a perfusion/metabolism match and nonviable segments showed significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P < 0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage: r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P < 0.0001)., Conclusion: In hypoperfused myocardium, electrical activity by NOGA mapping is more closely related to PET metabolic activity than to SPECT myocardial perfusion. As NOGA mapping does not differentiate hypoperfused myocardium with enhanced glucose utilization from normal myocardium, results from NOGA mapping need to be correlated with results from perfusion imaging to identify hypoperfused, yet viable, myocardium and to stratify patients for revascularization procedures.

Purpose: (11)C-metomidate (MTO), a marker of 11beta-hydroxylase, has been suggested as a novel positron emission tomography (PET) tracer for adrenocortical imaging. Up to now, experience with this very new tracer is limited. The aims of this study were (1) to evaluate this novel tracer, (2) to point out possible advantages in comparison with( 18)F-fluorodeoxyglucose (FDG) and (3) to investigate in vivo the expression of 11beta-hydroxylase in patients with primary aldosteronism., Methods: Sixteen patients with adrenal masses were investigated using both MTO and FDG PET imaging. All patients except one were operated on. Five patients had non-functioning adrenal masses, while 11 had functioning tumours(Cushing's syndrome, n=4; Conn's syndrome, n=5; phaeochromocytoma, n=2). Thirteen patients had benign disease, whereas in three cases the adrenal mass was malignant (adrenocortical cancer, n=1; malignant phaeochromocytoma, n=1; adrenal metastasis of renal cancer, n=1)., Results: MTO imaging clearly distinguished cortical from non-cortical adrenal masses (median standardised uptake values of 18.6 and 1.9, respectively, p<0.01). MTO uptake was slightly lower in patients with Cushing's syndrome than in those with Conn's syndrome, but the difference did not reach statistical significance. The expression of 11beta-hydroxylase was not suppressed in the contralateral gland of patients with Conn's syndrome, whereas in Cushing's syndrome this was clearly the case. The single patient with adrenocortical carcinoma had MTO uptake in the lower range., Conclusion: MTO could not definitely distinguish between benign and malignant disease. FDG PET, however, identified clearly all three study patients with malignant adrenal lesions. We conclude: (1) MTO is an excellent imaging tool to distinguish adrenocortical and non-cortical lesions; (2) the in vivo expression of 11beta-hydroxylase is lower in Cushing's syndrome than in Conn's syndrome, and there is no suppression of the contralateral gland in primary aldosteronism; (3) for the purpose of discriminating between benign and malignant lesions, FDG is the tracer of choice.

Unlabelled: Nuclear medicine plays an important role in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with (111)In-labeled somatostatin receptor analogs is a standard procedure for the detection and staging of NET. Based on the ability of NETs to store biogenic amines, this study evaluated whether 6-(18)F-fluoro-L-DOPA ((18)F-FDOPA) is a suitable PET tracer for NETs., Methods: Twenty-three patients with histologically verified NETs in advanced stages were consecutively enrolled in the study. All patients underwent PET with (18)F-FDOPA, CT, and SRS within 6 wk. In patients with discrepancies between nuclear medicine and radiologic methods, follow-up investigations were performed by CT, MRI, and ultrasound. (18)F-FDOPA PET with attenuation correction was done 30 and 90 min after injection from the neck to the upper legs. SRS was performed with (111)In-DOTA-D-Phe(1)-Tyr(3)-octreotide at 6 and 24 h. All images were read without knowledge of the results of the other modalities. In every patient, the following regions were evaluated separately: bones, mediastinum, lungs, liver, pancreas, and others, including the abdominal and supraclavicular lymph nodes, spleen, and soft- tissue lesions. The findings were confirmed by clinical examination. The nuclear medicine methods were compared against morphologic imaging, which was considered as gold standard., Results: The most frequently involved organs or regions were the liver (prevalence, 70%) and bone (52%), followed by mediastinal foci (31%), the lungs (22%), and the pancreas (13%). Fifty-two percent of patients had various lymphatic lesions. (18)F-FDOPA was most accurate in detecting skeletal lesions (sensitivity, 100%; specificity, 91%) but was insufficient in the lung (sensitivity, 20%; specificity, 94%); SRS yielded its best results in the liver (sensitivity, 75%; specificity, 100%); however, it was less accurate than PET in all organs. In about 40%, initial CT failed to detect bone metastases shown by PET that were later on verified by radiologic follow-up., Conclusion: (18)F-FDOPA PET performs better than SRS in visualizing NETs and may even do better than CT for bone lesions. SRS is essential to establish the usefulness of therapy with somatostatin analogs, yet is less accurate than (18)F-FDOPA PET for staging.

An increased uptake of bone-seeking radiopharmaceuticals into malignant bone lesions could further improve the diagnostic accuracy of routine bone scanning. The tracers used in clinical routine for bone scanning are methylene-diphosphonate (MDP), dicarboxypropane-diphosphonate (DPD) and ethylenediaminetetramethylene-phosphonate (EDTMP). MDP and DPD are usually labelled with 99mTc for diagnostic use, whereas EDTMP is labelled with 153Sm for therapeutic purposes. This study aimed to compare, for the first time, bone scanning with an improved preparation of 99mTc-EDTMP (by the addition of rhenium) (carrier-added) with 99mTc-DPD. Twenty malignant bone lesions were investigated in 10 patients. The ratios of bone lesion to soft tissue (BL/ST) and of bone lesion to normal bone (BL/NB) were compared 3 h after the injection of either compound. Quantitative analysis demonstrated a significant (P<0.05) difference in BL/ST ratio in favour of 99mTc-DPD. The BL/NB ratio was not significantly different. Visual image analysis resulted in a clinically comparable interpretation of imaging studies with the use of 99mTc-DPD and carrier-added 99mTc-EDTMP. These preliminary data support the concept of carrier addition to increase bone uptake by the modification of the complex structure of 99mTc-EDTMP. However, any advantage over conventional 99mTc-based tracers for bone scintigraphy in clinical use needs to be demonstrated in controlled trials.

Routine measurement of serum calcitonin (CT) has been recently proposed for all patients with neoplastic thyroid disease to detect clinically occult medullary thyroid carcinoma (MTC). Data on the prevalence of elevated CT levels in nonneoplastic thyroid disease or in healthy subjects have not been reported to date. Four hundred and fourteen consecutive patients with suspected thyroid disease and 362 healthy controls underwent thyroid examination with measurement of basal serum CT. Whenever serum CT was 10 pg/ml or more, a pentagastrin (PG) stimulation test was performed. Twenty-eight of 414 patients (6.8%) showed elevated basal serum CT levels, 15 of them with nonneoplastic thyroid disease, and the remaining 13 subjects with neoplastic thyroid disease. Four patients with abnormal PG testing (stimulated CT, > or = 100 pg/ml) were identified. Three of them had biochemical and sonographical evidence of thyroiditis. Elevated basal CT levels were significantly more frequent in patients with Hashimoto's thyroiditis (HT; P < 0.05). One female patient with HT had a 5-mm nodule, which was classified as MTC. None of the 6 out of 362 healthy controls with elevated basal CT (1.7%) presented an abnormal PG test. Our data suggest that basal CT measurements can be of use in the detection/screening of MTC not only in subjects with neoplastic thyroid disorders, but also in patients with immunological evidence of HT. They also confirm earlier reports on the essential value of PG stimulation testing, even when basal plasma CT levels are only modestly elevated, with regard to establishing the diagnosis of MTC or its premalignant associated conditions (micro-MTC and neoplastic C cell hyperplasia).

[(11)C]Flumazenil, a highly selective benzodiazepine antagonist is the most extensively used GABA(A) ligand for PET so far. To overcome half life disadvantages of (11)C a [(18)F]-labeled flumazenil derivative, 2'-[(18)F]fluoroflumazenil (FFMZ) was developed and biologically evaluated with respect to the GABA(A) receptor. Organ with the highest uptake was the pituitary gland. Brain uptake was high and followed the order cortex>thalamus>cerebellum>rest brain. Fluoroflumazenil displaced [(3)H]flumazenil binding from membrane GABA(A) receptors with an IC(50)value (3.5 nM) comparable to that of Flumazenil (2.8 nM). The presented data confirm the potential of [(18)F]FFMZ for PET imaging of the GABA-ergic system.

Unlabelled: This study presents and evaluates a model-based image analysis method to calculate from gated cardiac (18)F-FDG PET images diastolic and systolic volumes, ejection fraction, and myocardial mass of the left ventricle. The accuracy of these estimates was delineated using measurements obtained by MRI, which was considered the reference standard because of its high spatial resolution., Methods: Twenty patients (18 men, 2 women; mean age +/- SD, 59 +/- 12 y) underwent electrocardiography-gated cardiac PET and MRI to acquire a set of systolic and diastolic short-axis images covering the heart from apex to base. For PET images, left ventricular radius and wall thickness were estimated by model-based nonlinear regression analysis applied to the observed tracer concentration along radial rays. Endocardial and epicardial contours were derived from these estimates, and left ventricular volumes, ejection fraction, and myocardial mass were calculated. For MR images, an expert manually drew contours., Results: Left ventricular volumes by PET and MRI were 101 +/- 60 mL and 112 +/- 93 mL, respectively, for end-systolic volume and 170 +/- 68 mL and 189 +/- 99 mL, respectively, for end-diastolic volume. Ejection fraction was 44% +/- 13% by PET and 46% +/- 18% by MRI. The left ventricular mass by PET and MRI was 196 +/- 44 g and 200 +/- 46 g, respectively. PET and MRI measurements were not statistically significant. A significant correlation was observed between PET and MRI for calculation of end-systolic volumes (r = 0.93, SEE = 23.4, P < 0.0001), end-diastolic volumes (r = 0.92, SEE = 26.7, P < 0.0001), ejection fraction (r = 0.85, SEE = 7.4, P < 0.0001), and left ventricular mass (r = 0.75, SEE = 29.6, P < 0.001)., Conclusion: Model-based analysis of gated cardiac PET images permits an accurate assessment of left ventricular volumes, ejection fraction, and myocardial mass. Cardiac PET may thus offer a near-simultaneous assessment of myocardial perfusion, metabolism, and contractile function.

Objectives: Hashimoto's encephalitis is a term which describes encephalopathy associated with autoimmune thyroiditis, but it is not based on evidence, whether Hashimoto's encephalitis is a distinct clinical entity by itself. In previously reported cases of Hashimoto's encephalitis, abnormal brain perfusion studies have been reported. The aim of this study was to evaluate the prevalence of brain perfusion abnormalities in euthyroid patients with autoimmune thyroiditis., Methods: 99mTc Ethyl cystein dimer (ECD) single photon emission computed tomography (SPECT) studies were performed in a study group of 41 euthyroid patients with autoimmune thyroiditis and a matched control group of 35 healthy individuals. All study participants had a normal neurological investigation and a detailed neurological history taking. Individuals with known or suspected morphological brain abnormalities were excluded from the study. Zung's Self-Rating Anxiety Scale (SAS) and Zung's Self-Rating Depression Scale (SDS) were used to detect depression and mood disorders. Automatic quantification of perfusion was performed with both a voxel-based analysis as well as a volume-of-interest (VOI) based analysis of 46 predefined cortical and subcortical regions. The findings from both groups were compared to a reference template., Results: In the voxel-based analysis, there was a significant difference between patients and controls in the mean volume of perfusion defects deviating 2SD below the normal values (21.8 ml vs. 10.4 ml; P = 0.02). Hyperperfused areas, however, did not differ significantly between study patients and controls. A significant correlation of the perfusion defects with time since diagnosis of autoimmune thyroiditis was seen (r = 0.42). In the VOI-based analysis, abnormal regions were more frequent in the study group when compared to controls (P < 0.01) However, no topographic pattern was apparent. Regarding neurological findings, no significant difference was found between study patients and controls. However, both the SAS and SDS scores differed significantly between the two groups, but there was neither a correlation between the two scores and perfusion abnormalities nor an association with depression in our study group., Conclusions: These findings of impaired brain perfusion in patients with autoimmune thyroiditis further strengthen the hypothesis of a possible cerebral involvement in autoimmune thyroiditis in individual cases. The presence of cerebral hypoperfusion suggests a cerebral vasculitis as the most likely pathogenetic model.

Objective: Statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and widely used to treat hyperlipidaemia. Apart from their direct lipid-lowering effects, statins may also influence lipid metabolism through modulation of low-density lipoprotein (LDL) receptors. Basophils and mast cells have been reported to express LDL receptors and have been implicated in atherogenesis. The aim of this study was to investigate the effects of statins on the interactions of 125I-LDL with purified primary human blood basophils, a human basophil cell line, KU812, and a human mast cell line, HMC-1., Methods: Direct binding experiments were carried out with the primary basophils and KU812 as well as HMC-1 cells before and after pretreatment of the cells with atorvastatin, simvastatin, or cerivastatin. The effects of these three statins on the LDL-uptake and degradation as well as on thymidine incorporation in the cells were also studied., Results: Primary basophils, HMC-1 and KU812 cells expressed two classes of LDL binding sites. Exposure to atorvastatin, simvastatin or cerivastatin increased significantly ( P<0.05) the number of 125I-LDL binding sites on primary basophils and HMC-1 as well as KU812 cells. The effects of the statins were dose dependent. The statins also enhanced the uptake and degradation of LDL in primary basophils, HMC-1 and KU812 cells. The increase in the number of LDL binding sites induced by statins was abolished by mevalonic acid (200 micromol/l). Statins had no effect on the thymidine incorporation into the cells in an unstimulated condition., Conclusion: Our results provide evidence for the upregulation of LDL binding sites on human basophils and mast cells by statins. We hypothesise that effects of statins on the lipid metabolism might also involve basophils and mast cells.

11beta-Hydroxylase (CYP11B1, P45011beta) plays an important role in the biosynthesis of cortisol and aldosterone and has been shown to be a good target for the in vivo imaging of adrenocortical incidentalomas in nuclear medicine. [11C]Metomidate (MTO), a potent inhibitor of this enzyme, is used for positron emission tomography (PET) imaging of adrenocortical pathology. The synthesis of (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 2-[18F]fluoroethylester (FETO), a close analogue to MTO and etomidate (ETO), has been presented recently, and the present investigation aimed to characterise the in vivo distribution of FETO. Since ETO is a well-known anaesthetic drug acting via the GABAergic system, the interaction of FETO with GABAA receptors was also evaluated. Eighteen male Sprague-Dawley rats were injected with 1.73-3.06 MBq of FETO into a tail vein after venodilatation in a 40 degrees C water bath. Rats were sacrificed by exsanguination from the abdominal aorta under deep ether anaesthesia after 10 (n=6), 30 (n=6) or 60 min (n=6); organs were removed, weighed and counted. For binding experiments, rat cerebellar membranes were incubated for 90 min at 4 degrees C in TC-50 buffer, 150 mM NaCl and 2 nM of [3H]flunitrazepam in the absence or presence of 10 microM diazepam or various concentrations of ETO, MTO and FETO. In vivo evaluation evinced very high uptake in the adrenal glands (7.52%+/-1.19% ID/g at 30 min), followed by lung (1.18%+/-0.19% ID/g, 10 min), liver (0.59%+/-0.13% ID/g, 10 min) and duodenum (0.7%+/-0.29% ID/g, 60 min). No defluorination nor fluoroethyl-ester cleavage was observed. When brain regions were compared with the thalamus (the reference region), highest relative uptake was seen in the cortex (2.34), followed by "rest brain" (2.13) and cerebellum (1.96). FETO and ETO were able to increase the binding of [3H]flunitrazepam with similar potencies and to a comparable extent. It is concluded that FETO shows characteristics suitable for the imaging of adrenocortical pathology with PET. Binding experiments on GABA receptors demonstrate a comparable effect of FETO and ETO. Hence, FETO possibly could also be used to elucidate the function, dynamics and kinetics of narcotic drugs with PET.

Goals: When thyroid and other cancers are "cured" it is often assumed that the patients are able to resume their normal lives. This was a cross-sectional study to evaluate health-related quality of life (HRQOL) and to identify rehabilitation needs of patients with non-metastatic thyroid cancer under thyroxine supplementation therapy., Patients and Methods: Included in the study were 150 consecutive patients with differentiated thyroid cancer (age 52 +/- 14 years, range 25-83 years; male/female 39/111). All patients had a history of total thyroidectomy followed by radioiodine ablation, were free of metastatic disease and under levothyroxine treatment. The mean period since the diagnosis of thyroid cancer was 5.5 +/- 6 years (range 0-23 years). Health-related quality of life was evaluated using the SF-36 Health Survey. The findings were compared with sex- and age-matched reference values., Results: "Role-emotional" and "Vitality" were significantly lower ( P<0.001 and P<0.005, respectively) in the group as a whole ( n = 150). In the subgroup of patients with a recent (less than 1 year) diagnosis of thyroid cancer ( n = 51), however, the following subscales were significantly lower: "Mental Health" ( P<0.01), "Role-emotional" ( P<0.001), "Role-physical" ( P<0.005), "Social functioning" ( P<0.005) and "Vitality" ( P<0.001). Multiple regression analysis identified a significant positive correlation between "Mental Health", "Physical functioning", "Vitality", "Role-emotional" and "Social functioning" with the time since initial diagnosis, and there was also a positive correlation between "Physical functioning", "Bodily pain" and "Role-emotional" with male gender., Conclusions: These findings indicate that "Vitality", "Role-physical", "Mental Health", "Role-emotional" and "Social functioning" are significantly impaired during the first year after diagnosis. Thereafter, quality of life improves correlating with the time since initial diagnosis. However, "Vitality" and "Role-emotional" remain permanently impaired in thyroid cancer patients. A multidisciplinary rehabilitation concept should include psychological support and an early start to exercise to improve physical performance of these patients leading to better HRQOL and to help them fulfill their social role earlier.

Somatostatin receptor (SSTR) scintigraphy and gallium-67 citrate ((67)Ga) scintigraphy have been used for visualisation of Hodgkin's lymphoma and non-Hodgkin's lymphoma. However, experience with B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type is very limited. The aim of this study was to prospectively compare the (67)Ga scintigraphy results with those obtained by (111)In-DOTA- dPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOCT) and (111)In-DOTA-lanreotide ((111)In-DOTA-LAN) scintigraphy in patients with proven MALT-type lymphoma. Comparative scintigraphic examinations using (67)Ga, (111)In-DOTA-TOCT and (111)In-DOTA-LAN were performed in 18 patients (11 female and 7 male, median age 64+/-15 years) with histologically verified MALT-type lymphomas of various origin. Planar and single-photon emission tomography imaging acquisitions were performed after injection of a mean dose of 185+/-26 MBq (67)Ga and 165+/-20 MBq (111)In-DOTA-TOCT or (111)In-DOTA-LAN. All scintigraphic results were correlated with other conventional examinations including gastroscopy, colonoscopy, endosonoscopy, ophthalmologic investigation, CT of the thorax and abdomen and bone marrow biopsy. This comparative study showed that (67)Ga scintigraphy found abnormalities in 10 of 16 patients (63%) and detected 18 of 31 clinically involved sites (58%), but was false positive in three patients. (111)In-DOTA-TOCT found abnormalities in 9 of 15 patients (60%) and detected 15 of 27 clinical lesions (56%); it was false positive in two patients. (111)In-DOTA-LAN scintigraphy showed abnormalities in 7 of 11 patients (64%) and found 12 of 22 clinical lesions (55%). False-positive (111)In-DOTA-LAN scan results were found in two patients. For supra-diaphragmatic lesions, (67)Ga scintigraphy detected 12 of 16 sites (75%). (111)In-DOTA-TOCT scintigraphy revealed 7 of 15 lesions (47%). (111)In-DOTA-LAN showed 6 of 12 positive sites (50%). For infra-diaphragmatic involvement, the sensitivities of (67)Ga, (111)In-DOTA-TOCT and (111)In-DOTA-LAN were 40%, 67% and 60%, respectively. It is concluded that MALT-type lymphoma can be visualised by (67)Ga, (111)In-DOTA-TOCT and (111)In-DOTA-LAN scintigraphy. Although there were no statistically significant differences in patient-related and site-related sensitivities when using (67)Ga compared with (111)In-DOTA-TOCT and (111)In-DOTA-LAN, the sensitivity of (67)Ga tended to be superior to that of (111)In-DOTA-TOCT and (111)In-DOTA-LAN for supra-diaphragmatic lesions but inferior for infra-diaphragmatic involvement. In selected cases, the combination of (67)Ga and (111)In-DOTA-LAN or (111)In-DOTA-TOCT may increase the diagnostic efficiency in patients with MALT-type lymphoma.

PET with (R)-[O-methyl-11C] metomidate ([11C] MTO) is an attractive method for the characterisation of adrenal masses discriminating lesions of adrenal cortical origin from noncortical lesions. [11C] MTO was prepared by the reaction of [11C] methyliodide with the corresponding free acid. Three purification methods have been compared. The method of choice uses preparative HPLC with a ready-to-use weak acidic solvent.

Introduction: Several variables of health-related human behaviour have been analysed with regard to a possible association with lunar phases. The aim of this study was to evaluate a possible relation between the lunar cycle and the number of requests for appointments at an outpatient clinic. This variable has not been studied hitherto., Methods: We analysed a total number of 11,413 requests for appointments at our thyroid outpatient clinic during one year. Access to this clinic is not restricted, and all patients with known or suspected thyroid disease living in the area of Vienna may ask for an appointment. During the study period, 8,852 patients requested a follow-up appointment, and 2561 patients asked for a new appointment. We analysed a possible cyclic pattern in these requests using a nonlinear regression model based on both groups of patients., Results: A cosinus curve with a period of 29.531 days (the mean length of a lunar cycle) was significantly associated with the number of requests for both follow-up appointments (p = 0.007) and new appointments (p = 0.001). Requests for follow-up appointments had their highest peaks three days after the full moon, whereas requests for new appointments were most frequent five days afterwards., Conclusion: Our findings suggest that lunar phases may affect patients' requests for appointments at a thyroid outpatient clinic. To the best of our knowledge, this is the first study reporting a possible association between health-related behaviour and lunar phases using requests for appointments as a relevant variable. There is a need for more research into the mechanism underpinning this behaviour.

Impairment of the lacrimal glands after external radiation has been well documented, but there are only a few reports on the effects of radioiodine therapy on the lacrimal glands. Long-term effects of high-dose radioiodine therapy on tear secretion have not previously been studied. We investigated 175 eyes of 88 patients with a history of radioiodine therapy for thyroid carcinoma (68 females, 20 males; mean age 55+/-16 years, range 17-81 years) and compared them with a sex- and age-matched control group ( n=39). All patients had been given at least 2.96 GBq iodine-131 (maximal administered activity 22.3 GBq (131)I). An ophthalmological investigation was performed 64+/-71 months (range 3-317 months) after initial radioiodine therapy by a single ophthalmologist. Lacrimal gland function was evaluated with three different function tests. External eye morphology was considered, and detailed ophthalmological history-taking was performed. Patients with factors known to affect lacrimal gland function (contact lenses, autoimmune disorders, history of additional radiation exposure) were excluded from the study. A total of 81 patients (92%) had at least one abnormal function test indicating impaired lacrimal gland function. Schirmer's tear test was decreased (<10 mm/5 min) in 47 of the 88 patients and definitely abnormal (<5 mm/5 min) in 35 patients. A tear film break-up time of <10 s was found in 78 patients, and 62 patients had a definitely abnormal break-up time of <5 s. The lacrimal lipid layer was impaired in 43 patients. The function tests were all significantly altered in the study group as compared with the controls ( P<0.005, P<0.001, P<0.001, respectively). Both subjective symptoms of dry eye ( P<0.01) and changes in the external eye morphology ( P<0.001) were significantly more prevalent in the study group. Our findings suggest that in the majority of patients, lacrimal gland function may be permanently impaired after high-dose radioiodine therapy. All three layers of the tear film are involved and there is a pronounced long-term effect on the tear film stability.

Objective: Systemic mastocytosis is a hematologic neoplasm characterized by abnormal accumulation and growth of mast cells in one or more organ systems. We analyzed five patients with systemic mastocytosis referred for FDG positron emission tomography who had biopsy-proven mast cell infiltrates in various organs., Conclusion: Our findings indicate that FDG positron emission tomography is not useful for staging and follow-up of aggressive systemic mastocytosis.

The lipophilic cationic compound Tc-99m-tetrofosmin has been demonstrated to be a valuable tool for the detection of a variety of tumours. Tc-99m-tetrofosmin uptake by sarcomas in vitro as well as in primary tumours has been reported. Data on the visualisation of metastatic soft tissue sarcomas using this tracer are missing so far. Ten consecutive patients with histopathologically verified metastatic soft tissue sarcoma were included in the present study. Five patients had previously received cytotoxic treatment, the other five patients were chemonaive. All patients underwent whole body planar examination after administration of 500-550 MBq Tc-99m-tetrofosmin, and in case of lung metastases on CT scan, SPECT images were carried out. Non-physiological accumulation of the tracer was considered as a positive result. Scintigraphic results were compared to conventional imaging by means of MRI/CT scanning. Visualisation of distant metastases was achieved in five patients all of whom were chemonaive, while in the chemotherapeutically pretreated patient group (n=5) false negative results were seen. Progressive disease was confirmed by follow-up in all patients. Pulmonary metastases were visualised only in SPECT acquisition and not on planar images. In one patient with diffuse bone marrow infiltration (inflammatory myofibroblastic sarcoma) Tc-99m-tetrofosmin scintigraphy was positive, while CT showed a negative result. According to our results, detection of metastatic soft tissue sarcomas by Tc-99m-tetrofosmin scintigraphy was strongly dependent on the history of previous treatment of the patient. A positive finding before initiation of chemotherapy was not indicative for subsequent therapeutic response. In the staging of chemonaive patients with metastatic soft tissue sarcoma Tc-99m-tetrofosmin may provide some additional information.

Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much more sensitive than valsartan renography in detecting a clinically significant renal artery stenosis. Furthermore, our data suggest that other effects, such as that on the prostaglandin-bradykinin system, are of at least similar importance to ACE inhibition for the high diagnostic sensitivity of captopril renography regarding renovascular hypertension.

Objective: Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This study was performed (1) to analyse retrospectively patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bone metastases on survival., Patients and Design: We analysed 41 consecutive patients with bone metastases from differentiated thyroid carcinoma who had undergone thyroid surgery at Vienna University Hospital since 1966. The median follow-up time was 12 years. There were 24 females and 17 males with a mean age of 60 +/- 12 years. Primary tumour histology was follicular in 35 and papillary in six patients. Radioiodine treatment was performed in 32 with a mean administered activity of 27 +/- 24 GBq 131I. Metastases restricted to the skeleton were found in 22 whereas in 19 individuals additional extraskeletal distant metastases were seen. Twenty-seven patients had multiple bone metastases. In 21 individuals, up to five bone metastases were surgically removed with the intention of cure., Results: Univariate analysis identified total thyroidectomy (P = 0.003), lymph node surgery (P = 0.001), radioiodine therapy (P = 0.036), and the absence of extraskeletal distant metastases (P = 0.017) as significant predictors of survival. Multivariate analysis failed to identify significant prognostic factors. In the subgroup of patients with distant metastases limited to the bones, univariate analysis identified, in addition to thyroid and lymph node surgery, the surgical extirpation of the bone metastases as a significant prognostic factor associated with improved survival (P = 0.025)., Conclusions: These findings indicate that in patients without additional extraskeletal distant metastases, the radical surgical extirpation of bone metastases from differentiated thyroid carcinoma might be associated with improved survival.

Background: The prognosis of systemic vasculitis, for instance Wegener's granulomatosis (WG), was greatly improved by the introduction of immunosuppressive treatment. However, relapses are frequent and predictors are scarce. 111In-leukocytes have been found to indicate unknown manifestations of WG and to predict later relapse. We prospectively investigated the value of 99mTc-Exametazime (99mTc-HMPAO)-labeled leukocytes with regard to specific patterns and for their usefulness in the follow-up of patients with WG., Methods: The vasculitis group consisted of 8 patients with WG and 2 with idiopathic necrotizing glomerulonephritis (ING). Seven patients with different inflammatory diseases served as controls. Leukocyte labeling with 99mTc-HMPAO was done using a slightly modified Hammersmith protocol. Cell viability after labeling was verified in vivo by the exclusion of early lung and splenic uptake and in vitro by means of propidium iodide and FACS analysis. Static gamma camera images from the head, chest, abdomen, and pelvis were obtained up to 18 hours after injection of approximately 300 MBq 99mTc-HMPAO-labeled leukocytes. Scintigrams were analyzed visually; for semiquantitative analysis ROIs were drawn over the nasal region, the right lung, kidneys, and liver., Results: Increased nasal leukocyte accumulation was found in 7/8 patients with WG and in 2/2 patients with ING. Of 2 patients who had a relapse 6 months later, one presented with, and one without nasal uptake. The kidney/liver ratio was higher in controls (0.24 +/- 0.07 vs. 0.37 +/- 0.11, p < 0.05). Distinct to moderate lung uptake was observed in 2 patients with WG and in one with ING. No correlation was found between scintigraphic results, medication, ANCA status or cretinine levels., Conclusion: Nasal leukocyte accumulation is increased in systemic vasculitis, independent of the immunosuppressive treatment and later clinical course. However, this finding is not specific for vasculitis. 99mTc-HMPAO leukocyte scintigraphy failed to indicate or exclude a later relapse and is therefore not suitable as a diagnostic tool in the management of patients with systemic vasculitis.