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The current study aimed to determine the optimum diagnostic imaging technique out of magnetic resonance imaging (MRI), 18F‑fludeoxyglucose positron emission tomography/computed tomography ([18F] FDG‑PET/CT, otherwise known as PET/CT) and [18F] FDG‑PET/MRI (otherwise known as PET/MRI) for the pelvic lymph node staging (N‑staging) of untreated cervical carcinoma (CC). A total of 27 patients were included in the present study. All patients had undergone pre‑treatment with PET/CT and MRI ≤45 days prior to undergoing a lymphadenectomy. The results from PET (separated from PET/CT), MRI and the statistically combined results of (virtual) PET/MRI were compared to those from histological analyses (the gold standard). A per‑patient‑based analysis of the detection of pelvic lymph node metastases indicated that PET/MRI had a sensitivity of 64%. The specificity of PET/CT and MRI were 69 and 62%, respectively. The positive predictive value (PPV) was 69 and 64% for PET/CT and MRI, respectively. The negative predictive value (NPV) was 64 and 62% for PET/CT and MRI, respectively. The sensitivity of the PET‑guided PET/MRI and the MRI‑guided PET/MRI was 64% for both. The specificity of the PET‑guided PET/MRI and the MRI‑guided PET/MRI was 77 and 62%, respectively. The PPV was 75% for PET‑guided PET/MRI and 64% for MRI‑guided PET/MRI, and the NPV was 67 and 62%, respectively. PET/CT and the virtual PET/MRI exhibited the same low sensitivity (64%). PET/MRI exhibited slightly better results than PET/CT regarding specificity (77 vs. 69%, respectively), PPV (75 vs. 69%, respectively) and NPV (67 vs. 64%, respectively). The results of the present study suggested that PET/CT and MRI are not optimal diagnostic modalities, and that PET/MRI does not necessarily lead to better results than PET/CT, in the pelvic N‑staging of CC. [ABSTRACT FROM AUTHOR]

Background: The association of subclinical hypothyroidism (SCH) with increased risk for cardiovascular disease is still controversial. This study aimed to examine coronary vascular reactivity by positron emission tomography (PET) in asymptomatic patients with SCH before and after levothyroxine (LT4) supplementation. Methods: Ten patients (7 women and 3 men; mean age 43±15 years) with untreated autoimmune SCH, defined by elevated levels of thyroid-stimulating hormone (mean TSH: 16.9±11.3 μU/mL), normal levels of free thyroxine (0.9±0.1 μg/mL), free triiodothyronine (3.2±0.4 pg/mL), and positive thyroid peroxidase antibodies were studied. Eight euthyroid subjects with similar low-risk cardiovascular risk profile served as controls. Myocardial blood flow (MBF) and coronary flow reserve (CFR) were quantitatively assessed with rest/stress N-13 ammonia PET at baseline and after 6 months of LT4 replacement therapy (given only to patients). Results: At baseline, stress MBF and CFR corrected (c) for rate pressure product (RPP) and myocardial vascular resistance (MVR) during stress were significantly reduced in SCH compared with controls (stress MBF: 2.87±0.93 vs. 4.79±1.16 mL/g/min, p=0.003; CFR: 2.6±0.73 vs. 4.66±1.38, p=0.004; MVR: 40.14±18.76 vs. 20.47±6.24 mmHg/mL/min, p=0.02). Supplementation therapy with LT4 normalized TSH in all subjects and was associated with an increase in CFR (2.6±0.73 vs. 3.81±1.19, p=0.003) and with a tendency toward a decrease in MVR. Differences in CFR between SCH and controls were also seen after correction of resting MBF for RPP. Conclusions: In asymptomatic subjects with SCH due to thyroid autoimmunity, coronary microvascular function is impaired and improves after supplementation with LT4. This may partially explain the increased cardiovascular risk attributed to SCH. [ABSTRACT FROM AUTHOR]

Background. The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer 18F-fluoroazomycin-arabinoside (18FAZA ). Material and methods. Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm3 (+/− 67, SD). Dynamic and static 18FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/− concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk. Results. Five patients had visually identifiable tumours on 18FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five 18FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten 18FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/−12, SD). Conclusion. PET imaging with 18FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of 18FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance. [ABSTRACT FROM AUTHOR]

The higher prevalence rates of depression and anxiety disorders in women compared to men have been associated with sexual dimorphisms in the serotonergic system. The present positron emission tomography (PET) study investigated the influence of sex on the major inhibitory serotonergic receptor subtype, the serotonin-1A (5-HT1A) receptor. Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [ carbonyl-11C]WAY-100635. Effects of age or gonadal hormones were excluded by restricting the inclusion criteria to young adults and by controlling for menstrual cycle phase. The 5-HT1A receptor BPND was quantified using (1) the ‘gold standard’ manual delineation approach with ten regions of interest (ROIs) and (2) a newly developed delineation method using a PET template normalized to the Montreal Neurologic Institute space with 45 ROIs based on automated anatomical labeling. The 5-HT1A receptor BPND was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BPND values in every region investigated, with a borderline significant sex difference in the hypothalamus ( p = 0.012, uncorrected). There was a high intersubject variability of the 5-HT1A receptor BPND within both sexes compared to the small mean differences between men and women. To conclude, when measured in the follicular phase, women do not differ from men in the 5-HT1A receptor binding. To explain the higher prevalence of affective disorders in women, further studies are needed to evaluate the relationship between hormonal status and the 5-HT1A receptor expression. [ABSTRACT FROM AUTHOR]

Purpose and Methods: Regional overexpression of the multidrug transporter P-glycoprotein (P-gp) in epileptic brain tissue may lower target site concentrations of antiepileptic drugs and thus contribute to pharmacoresistance in epilepsy. We used the P-gp substrate R-[11C]verapamil and positron emission tomography (PET) to test for differences in P-gp activity between epileptogenic and nonepileptogenic brain regions of patients with drug-resistant unilateral temporal lobe epilepsy (n = 7). We compared R-[11C]verapamil kinetics in homologous brain volumes of interest (VOIs) located ipsilateral and contralateral to the seizure focus. Results: Among different VOIs, radioactivity was highest in the choroid plexus. The hippocampal VOI could not be used for data analysis because it was contaminated by spill-in of radioactivity from the adjacent choroid plexus. In several other temporal lobe regions that are known to be involved in seizure generation and propagation ipsilateral influx rate constants K1 and efflux rate constants k2 of R-[11C]verapamil were descriptively increased as compared to the contralateral side. Parameter asymmetries were most prominent in parahippocampal and ambient gyrus ( K1, range: −3.8% to +22.3%; k2, range: −2.3% to +43.9%), amygdala ( K1, range: −20.6% to +31.3%; k2, range: −18.0% to +38.9%), medial anterior temporal lobe ( K1, range: −8.3% to +14.5%; k2, range: −14.5% to +31.0%) and lateral anterior temporal lobe ( K1, range: −20.7% to +16.8%; k2, range: −24.4% to +22.6%). In contrast to temporal lobe VOIs, asymmetries were minimal in a region presumably not involved in epileptogenesis located outside the temporal lobe (superior parietal gyrus, K1, range: −3.7% to +4.5%; k2, range: −4.2% to +5.8%). In 5 of 7 patients, ipsilateral efflux ( k2) increases were more pronounced than ipsilateral influx ( K1) increases, which resulted in ipsilateral reductions (10%–26%) of R-[11C]verapamil distribution volumes (DV). However, for none of the examined brain regions, any of the differences in K1, k2 and DV between the epileptogenic and the nonepileptogenic hemisphere reached statistical significance (p > 0.05, Wilcoxon matched pairs test). Conclusions: Even though we failed to detect statistically significant differences in R-[11C]verapamil model parameters between epileptogenic and nonepileptogenic brain regions, it cannot be excluded from our pilot data in a small sample size of patients that regionally enhanced P-gp activity might contribute to drug resistance in some patients with temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GIST has been shown to over-express c-KIT (CD117), the receptor tyrosine kinase. Imatinib (STI571 or Glivec) is a new type of tyrosine kinase inhibitor that selectively inhibits various tyrosine kinases and has been successfully used to treat GIST. In this study we have compared the results of F-18 FDG PET with those of CT in patients with GIST before and early after the treatment with Imatinib. Methods: The performance of CT and FDG PET imaging in the staging and follow-up of GIST lesion was retrospectively evaluated and compared in 15 patients with 67 suspicious lesions. All patients were examined before and after treatment with Imatinib. Findings of CT and FDG PET were compared on both patient- and lesion-based basis for the whole group and for anatomic locations. Results: Overall 67 lesions were detected in both pre-therapeutic FDG PET and CT imaging. In the pre-treatment studies there was no significant difference between detected lesions on FDG PET and CT (p = 0.19). However, after treatment with Imatinib (follow-up interval of 30 ± 16 days), FDG PET predicted response to therapy earlier than CT in 18% of lesions and 14% of patients, respectively. There was no significant difference in the density of malignant lesions by means of Hounsfield unit (HU) in the baseline PET in comparison to the early post-therapeutic investigations (93 ± 16 vs. 90 ± 22). Conclusion: For treatment monitoring of Imatinib in GIST patients, FDG PET gives more precise information of active state of disease compared with CT. [ABSTRACT FROM AUTHOR]

Background: Since Nichols Institute Diagnostics (NID) ended production of their automated calcitonin immunoassay, evaluation of an alternative calcitonin assay was necessary. Methods: Calcitonin measured by the NID procedure was compared with a test from Diagnostic Products Corporation (DPC). Calcitonin was also measured by assays from DiaSorin (DS) and Scantibodies (SC). Results: In 187 samples, detection failed either by NID (39%) or DPC (96%) assay; in 35% of samples, the tests agreed for non-measurable calcitonin. The regression line DPC=0.78×NID−0.3 (r=0.998) fitted results from 236 samples with detectable calcitonin. A linear relationship, albeit with scattering at low concentrations, was observed. Importantly, stimulation by pentagastrin above basal calcitonin concentrations yielded similar results with both assays. Comparisons (DPC=0.80×DS−3.4 and DPC=0.81×SC−1.1) confirmed an aberrant calibration of the DPC test. To overcome the method bias, we propose a multiplication factor of 0.8 to convert NID to DPC results. Conclusions: Apparently due to non-specific effects, the DS and SC assays produced calcitonin results in samples from completely thyroidectomized patients, while the DPC assay correctly failed to detect calcitonin. Thus, the DPC assay on an Immulite® 2000 analyzer may be used as a more accurate substitute for NID if the different calibration is noted. Clin Chem Lab Med 2007;45:662–6. [ABSTRACT FROM AUTHOR]

Previous studies have investigated the occupancy of the serotonin reuptake transporter (SERT) after clinical doses of citalopram and other selective serotonin reuptake inhibitors. In the present study, the occupancies of SERT after multiple doses of escitalopram and citalopram were compared using the radioligand [123I]ADAM and single photon emission computed tomography (SPECT). Fifteen healthy subjects received escitalopram 10 mg/day ( n = 6) or citalopram 20 mg/day ( n = 9) for a total of 10 days. SERT occupancies in midbrain were determined with SPECT and [123I]ADAM at three different time points: at baseline (no medication) and at 6 and 54 h after last drug intake. At 6 h after the last dose, mean SERT occupancies were 81.5 ± 5.4% (mean±SD) for escitalopram and 64.0 ± 12.7% for citalopram ( p < 0.01). At 54 h after the last dose, mean SERT occupancies were 63.3 ± 12.1% for escitalopram and 49.0 ± 11.7% for citalopram ( p < 0.05). The plasma concentrations of the S-enantiomer were of the same magnitude in both substances. For both drugs, the elimination rate of the S-enantiomer in plasma was markedly higher than the occupancy decline rate in the midbrain. The significantly higher occupancy of SERT after multiple doses of escitalopram compared to citalopram indicates an increased inhibition of SERT by escitalopram. The results can also be explained by an attenuating effect of R-citalopram on the occupancy of S-citalopram at the SERT. [ABSTRACT FROM AUTHOR]

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 (67Ga) scintigraphy results with those obtained by positron emission tomography (PET) using 11C-acetate in patients with HCC. Methods: We prospectively analysed 21 patients (mean age, 64±11 years) with histopathologically verified HCC undergoing 11C-acetate PET and 67Ga scintigraphy. 67Ga scans were not performed in three of these 21 patients due to the exacerbation of the disease. Whole-body 11C-acetate PET were performed following intravenous injection of 850 MBq of 11C-acetate. For 67Ga scintigraphy, whole-body, planar and single photon emission computed tomography imaging acquisitions were performed after intravenous application of a mean dose of 189 MBq 67Ga. Results: 67Ga 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. 11C-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 67Ga scintigraphy nor the conventional computed tomography have shown the lesions, which were clearly demonstrated by the 11C-acetate PET. Conclusion: Our results indicate significantly higher sensitivity and specificity of 11C-acetate PET than 67Ga scan in detection of HCC lesions. This study suggests that imaging with 11C-acetate PET might play a potential role in the diagnostic workup of patients with HCC. [ABSTRACT FROM AUTHOR]

Aim Recombinant human thyrotropin (rhTSH) is a new option for diagnostic follow-up in patients with differentiated thyroid cancer (DTC). Iodine kinetics after administration of rhTSH is controversially discussed. The aim of our study was to compare the time course of radioiodine in tumour and normal tissue during periods of TSH elevation in patients in a hypothyroid state (HS) following hormone withdrawal, with those under euthyroidism (ES) after the administration of rhTSH. Patients and methods We investigated four patients who had undergone near-total thyroidectomy and were suffering from metastatic disease. Dosimetric calculations were performed using tumour and whole-body uptake, and background measurements from 123-iodine scans performed 0, 4, 24 and 48 h after the application of 123I. Results All patients had lesser uptake of 123I under rhTSH stimulation than after hormone withdrawal. The median maximum TG (thyroglobulin) levels were 733·1 ng/ml with HS and 548·0 ng/ml with ES. The median half-life in tumour tissue was 39·8 h (mean 65·9, range 11·5–194·0) with HS and 21·9 h (mean 38·7, range. 8·7–113·9) with ES. The median uptake dose in per cent in tumour tissue was 0·08 (mean 0·15, range 0·04–0·6) with HS and 0·05 (mean 0·08, range 0·03–0·2) with ES. Furthermore, the cumulative activity in metastatic tissue was lower after rhTSH than during hypothyroidism, with considerable variations between individual lesions. Conclusion In our small group of DTC patients with metastatic disease, the effectiveness of radioiodine therapy following rhTSH was anticipated to be less than that in individuals who were hypothyroid after levothyroxine (L-T4) withdrawal. Endogenous TSH stimulation of metastatic thyroid cancer with radioiodine should not be performed without prior target tumour lesion dosimetry with 123I. [ABSTRACT FROM AUTHOR]

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 [11C]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.Clinical Pharmacology & Therapeutics (2006) 80, 216–227; doi: 10.1016/j.clpt.2006.05.007 [ABSTRACT FROM AUTHOR]

Purpose: 11β-Hydroxylase is a key enzyme in the biosynthesis of adrenocortical steroid hormones and is a suitable target for the imaging of the adrenal cortex. [11C]Metomidate (MTO), [11C]etomidate (ETO) and desethyl-[18F]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 µmol for FETO, 162.0 µmol for MTO and 168.6 µmol for ETO. Limiting velocities were 1.54 µmol/min (FETO), 1.47 µmol/min (MTO) and 1.35 µmol/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. [ABSTRACT FROM AUTHOR]

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 11β-hydroxylase inhibitor, [18F] FETO, in rats displaying high tracer accumulation in the adrenals. In this study, we aimed to investigate for the first time the potency of [18F]FETO as a PET tracer for the adrenal cortex in humans. Methods: An average preparation yielded 1-2 GBq of [18F]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 [18F] 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: [18F]FETO distribution was similar in all scanned volunteers. Visually, pronounced accumulation of [18F] 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: [18F]FETO is a valuable tracer for adrenocortical PET imaging, combining the longer half-life of 18F with a high 11β-hydroxylase selectivity. In accordance with our findings in rats, FETO PET revealed very high accumulation in the adrenal glands in healthy volunteers. [ABSTRACT FROM AUTHOR]

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 99mTc-MDP, 153Sm-EDTMP and 18F-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 µmol of radiolabelled PPs or 25 MBq 18F-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. [ABSTRACT FROM AUTHOR]

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-DPhe¹-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-DOTATOC 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-DOTALAN 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. [ABSTRACT FROM AUTHOR]

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. 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). T cells from patients with a high TPOAb titre (group I) had significantly higher percentages of cells producing IFN-γ 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-γ 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-β. Similarly, patients in group I also showed higher percentages of TNF-α positive cells than healthy donors (group III). In this case, cells expressing TNF-α alone as well as cells coexpressing TNF-α and IFN-γ 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). 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. [ABSTRACT FROM AUTHOR]

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 [11C]verapamil could be detected in healthy volunteers differing in ABCB1 haplotypes. [Copyright &y& Elsevier]

Background: Measurement of myocardial blood flow (MBF) by dynamic nitrogen 13 ammonia (NH3) 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 NH3 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. [Copyright &y& Elsevier]

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 μg/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. [ABSTRACT FROM AUTHOR]

In the last decade radiolabeled tropane analogs based on β-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 β-CIT by a fluoroethyl ester. The preparation and ex vivo evaluation of this new β-CIT-analog ([18F]FE@CIT) is presented here. Precursor and standard were prepared from β-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°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/μmol. An average 30 μAh 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 μm 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. Synapse 55:73-79, 2005. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose. 11C-metomidate (MTO), a marker of 11β-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 18F-fluorodeoxyglucose (FDG) and (3) to investigate in vivo the expression of 11β-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 11β-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 11β-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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

11β-Hydroxylase (CYP11B1, P450[sub11β]) 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. [[sup11]C]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-[[sup18]F]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 GABA[subA] 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°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°C in TC-50 buffer, 150 mM NaCl and 2 nM of [³H]flunitrazepam in the absence or presence of 10 μM 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 re- gions 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. [ABSTRACT FROM AUTHOR]

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 μmol/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. [ABSTRACT FROM AUTHOR]

Somatostatin receptor (SSTR) scintigraphy and gallium-67 citrate ([sup 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 [sup 67]Ga scintigraphy results with those obtained by [sup 111]In-DOTA-dPhe[sup 1]-Tyr[sup 3]-octreotide ([sup 111]In-DOTA-TOCT) and [sup 111]In-DOTA-lanreotide ([sup 111]In-DOTA-LAN) scintigraphy in patients with proven MALT-type lymphoma. Comparative scintigraphic examinations using [sup 67]Ga, [sup 111]In-DOTA-TOCT and [sup 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 [sup 67]Ga and 165±20 MBq [sup 111]In-DOTA-TOCT or [sup 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 [sup 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. [sup 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. [sup 111]In-DOTA-LAN scintigraphy showed abnormalities in 7 of 11 patients (64%) and found 12 of 22 clinical lesions (55%). False-positive [sup 111]In-DOTA-LAN scan results were found in two patients. For supra-diaphragmatic lesions, [sup 67]Ga scintigraphy detected 12 of 16 sites (75%). [sup 111]In-DOTA-TOCT scintigraphy revealed 7 of 15 lesions (47%). [sup 111]In-DOTA-LAN showed 6 of 12 positive sites (50%). For infra-diaphragmatic involvement, the sensitivities of [sup 67]Ga, [sup 111]In-DOTA-TOCT and [sup 111]In-DOTA-LAN were 40%, 67% and 60%, respectively. It is concluded that MALT-type lymphoma can be visualised by [sup 67]Ga, [sup 111]In-DOTA-TOCT and [sup 111]In-DOTA-LAN scintigraphy. Although there were no statistically significant differences in patient-related and site-related sensitivities when using [sup 67]Ga compared with [sup 111]In-DOTA-TOCT and [sup 111]In-DOTA-LAN, the sensitivity of [sup 67]Ga tended to be superior to that of [sup 111]In-DOTA-TOCT and [sup 111]In-DOTA-LAN for supra-diaphragmatic lesions but inferior for infra-diaphragmatic involvement. In selected cases, the combination of [sup 67]Ga and [sup 111]In-DOTA-LAN or [sup 111]In-DOTA-TOCT may increase the diagnostic efficiency in patients with MALT-type lymphoma. [ABSTRACT FROM AUTHOR]

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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 [sup 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... [ABSTRACT FROM AUTHOR]

Examines the superiority of angiotensin converting enzyme (ACE) to angiotensin receptor blockade for renography in renal artery stenosis. Demonstration of renovascular hypertension by captopril renography; Performance of captopril, valsartan, and baseline renography; Evaluation of the alterations in renographic curves after intervention.

Summary 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 131 I. 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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the usefulness of Tc-99m-HIG scintigraphy in patients with Sjögren's syndrome.Methods: Twelve consecutive patients with verified secondary Sjögren's syndrome were included in this prospective study. The control group consisted of seven patients with Lupus erythematosus; none of them showed clinical signs of Sjögren's syndrome. Planar and SPECT images of the head were performed six hours after i.v. administration of Tc-99m HIG.Results: Eleven out of twelve patients with secondary Sjögren's syndrome showed a positive result, while one was false negative. Tracer accumulation in patients with positive scintigraphy varied. All patients of the control group were negative.Conclusion: Our data in a limited number of patients suggest that Tc-99m HIG scintigraphy could be a modality with high sensitivity and specificity for the diagnosis of Sjögren's syndrome and can provide objective information on the severity of the disease. [ABSTRACT FROM AUTHOR]

Since the introduction of a quick intraoperative parathyroid hormone (QPTH) assay, complete removal of hyperfunctioning parathyroid tissue can be proven during surgery. We report on a scintigraphically and biochemically documented patient with persistent primary hyperparathyroidism (PHPT) caused by suppressed hyperfunctioning parathyroid tissue. A left lower enlarged parathyroid gland was resected by minimally invasive open parathyroidectomy. QPTH measurements confirmed complete resection of hyperfunctioning tissue and histology showed a tumorous enlarged left lower parathyroid gland. The patient was normocalcemic until 1 month after surgery, when serum calcium increased again. A MIBI scan 6 months after surgery showed no evidence of hyperfunctioning parathyroid tissue. After an increase of PTH, a third MIBI scan another 3 months later was performed. Increased tracer uptake behind the lower pole of the right thyroid lobe was seen and confirmed by ultrasonography. Another tumorous enlarged parathyroid gland was removed. These findings support the hypothesis that smaller yet abnormal parathyroid glands can be suppressed and may become hypersecretory if left in situ after surgical removal of the larger gland.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: The aim of this paper is to describe the imaging pattern of focal nodular hyperplasia (FNH) by [sup 18]F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Methods: Eight consecutive asymptomatic patients with histologic proof of FNH underwent 18F-FDG PET imaging. The lesions were found incidentally. The 18F-FDG PET imaging was performed with a dedicated PET tomograph after intravenous injection of 300-370 MBq 18F-FDG. The 18F-FDG accumulation in the lesions was (semi)quantified by calculating the standardized uptake value (SUV) and SUV has been corrected for the lean body mass (LBM). Eight patients with liver metastases spread from melanoma (n=2) and colorectal carcinoma (n=6) served as controls. The size of the FNH lesions and of the control group ranged from 2.0 to 8.5 cm (mean 4.83 cm±2.37) and from 1.5 to 6 cm (mean 3.28±1.52), respectively. Results: While in malignant liver lesions the accumulation of 18F-FDG was significantly increased, all FNH lesions showed normal or even decreased accumulation of 18F-FDG. In FNH lesions, SUV ranged between 1.5 and 2.6 (mean 2.12±0.38), whereas all liver metastases showed an increased SUV ranging between 6.20 and 16.00 (mean 10.07±3.79). The SUV corrected for LMB (SUV[sub LBM]) was similar to the SUV and ranged between 0.9 and 2.2 (mean 1.81±0.41) for FNH and between 5.9 and 16.3 (mean 9.15±4.03), respectively. Conclusion: In contrast to liver metastases, there is no increased glucose metabolism in FNH in vivo. The imaging feature of FNH by 18F-FDG-PET imaging is not specific for FNH; however, it may be helpful to differentiate FNH from liver metastases in cancer patients if radiological methods are not diagnostic. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether the hepatic uptake of dialysed technetium-99m labelled low-density lipoprotein (Tc-LDL) reflects the hepatic LDL receptor activity and to what extent the non-LDL receptor-dependent Tc-LDL uptake by non-parenchymal cells relates to the diagnostic utility of quantitative Tc-LDL scintigraphy of the liver. New Zealand White rabbits and Watanabe Heritable Hyperlipidaemic rabbits, which were sacrificed 24 h after simultaneous injection of Tc-LDL and iodine-125 labelled LDL, were clearly discriminated by their hepatic Tc-LDL uptake according to their genetically different hepatic LDL receptor activity. Yet the hepatic Tc-LDL uptake exceeded the I-LDL uptake in all animals. The different hepatic uptake of the tracers was elucidated in the isolated perfused rat liver and was due to rapid intracellular degradation and the release of low molecular catabolites of I-LDL. In contrast, Tc activity was trapped in the liver. Analysis of biliary Tc activity provided evidence for the excretion of Tc-labelled apolipoprotein B. The amount of biliary excreted protein-bound Tc was linked to total hepatic Tc-LDL uptake and presumably reflected LDL receptor-mediated apolipoprotein excretion. Collagenase liver perfusion in Sprague-Dawley rats 90 min following simultaneous injection of Tc- and I-LDL and subsequent cell separation by gradient centrifugation revealed that Tc-LDL and I-LDL had a comparably low uptake into non-parenchymal cells; thus its contribution can be neglected for scintigraphic purposes. Planar scintigraphy was performed in New Zealand White and Watanabe Heritable Hyperlipidaemic rabbits. The different hepatic LDL receptor activities of the two groups were reflected by the slope of the liver/heart ratios over 24 h post injection and correlated well with their respective cumulative hepatic Tc-LDL uptake. Thus, we have been able to show that Tc-LDL scintigraphy using dialysed Tc-LDL can quantitate different genetically determined hepatic LDL receptor activities. The finding of the biliary excretion of Tc-labelled apolipoprotein B deserves further attention for its possible diagnostic utility. [ABSTRACT FROM AUTHOR]

The goal of the present study was to optimize technetium-99m labelling of low-density lipoprotein (LDL) and to investigate the in vitro and in vivo properties of the tracer to determine whether its application for quantitative scintigraphy of hepatic LDL receptor activity is feasible. LDL labelled with iodine-125 by the iodine monochloride method was used as a reference tracer. Comparison of different assessments of radiochemical purity [trichloro-acetic acid precipitation (%ppTCA), paper chromatography, size-exclusion chromatography and chloroform-methanol extraction] exhibited %ppTCA to be superior as a parameter of tracer quality. In spite of a high radiochemical purity immediately after labelling, modifications of Tc labelling of LDL did not overcome the poor long-term stability of the tracer. Subsequent dialysis in phosphate buffer over about 3 h sufficiently increased the long-term stability in vitro and in vivo. The competitive recognition of dialysed Tc-LDL and I-LDL with native LDL by high-affinity binding sites was demonstrated in human hepatoma cells (HepG2) and human fibroblasts. Biodistribution data of simultaneously injected Tc-LDL and I-LDL in New Zealand White rabbits showed a high uptake of both tracers in tissues with high LDL receptor activity, yet Tc-LDL uptake exceeded I-LDL uptake by two- to sevenfold. In contrast to I-LDL, Tc-LDL showed a higher unspecific uptake into the bone marrow and the spleen, suggesting an additional uptake mechanism probably via the scavenger pathway. Curve deconvolution of plasma clearance in five female New Zealand White rabbits and five male hyperlipidaemic patients again showed a marginally different biokinetic behaviour of Tc-LDL and I-LDL. It is concluded that dialysis of Tc-LDL substantially increases long-term stability, which is essential for quantification purposes, and that the dialysed tracer has retained its biological integrity as it is recognized by the LDL receptor in vitro. It remains to be determined to what extent the estimation of hepatic LDL receptor activity by quantitative Tc-LDL scintigraphy is influenced by the different biokinetic behaviour of Tc-LDL and I-LDL. [ABSTRACT FROM AUTHOR]

The feasibility of using I-heptadecanoic acid (HDA) as a metabolic tracer was studied. Different administration routes of HDA were compared. An intracoronary bolus injection was given to calves ( n=3), and an intravenous injection was given to patients ( n=4). In addition, we examined the influence of 4-h halothane anesthesia in calves and in patients the impact of an insulin (1.5 IU/kg)+ glucose (1.5 g/kg) infusion on the myocardial kinetics of HDA. Data were accumulated with a scintillation probe in calves ( t=50 min) and a gamma camera in patients (t=70 min). In calves after an intracoronary bolus injection of HDA the myocardial time-activity curve could be described by two exponentials. The mean elimination halftime of the initial phase ( t 1/2) was 7.3 min and that of the second phase ( t 1/2) was 35 min. The ratio of the size of the initial and second component at t was 0.93. Halothane anesthesia prolonged the elimination half-times and reduced the component ratio. The biphasic behavior of the myocardial time-activity curve was maintained in patients after intravenous administration of HDA under basal conditions (initial t 1/2=8.4 min). However, during infusion of insulin+glucose the decline in the myocardial activity was prolonged and monoexponential. This data shows that insulin glucose, interfering with fatty acid metabolism, influences the myocardial washout of HDA, and thus support its use as a metabolic tracer. [ABSTRACT FROM AUTHOR]