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PURPOSE To determine whether interim F-FDG PET or interim diffusion-weighted magnetic resonance imaging (DWI) can predict the end-of-treatment (EOT) outcome after immunotherapy in patients with FDG-avid extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). MATERIALS AND METHODS Patients with untreated MALT lymphoma prospectively underwent whole-body F-FDG PET/CT and DWI before treatment (baseline), and after three cycles (interim) of rituximab-based immunotherapy. Maximum and mean standardized uptake values (SUVmax, SUVmean), and minimum and mean apparent diffusion coefficients (ADCmin, ADCmean), were measured for up to three target lesions per patient. Rates of change between baseline and interim examinations (ΔSUVmax, ΔSUVmean, ΔADCmin, and ΔADCmean) were compared, using ANOVAs, between the four end-of-treatment (EOT, after six cycles of immunotherapy) outcomes: complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). RESULTS Fifteen patients with 25 lesions were included. Lesion-based post hoc tests showed significant differences between CR and PR for ΔSUVmax (P < 0.001), ΔSUVmean (P < 0.001), and ΔADCmin (P = 0.044), and between CR and SD for ΔSUVmax (P < 0.001), ΔSUVmean (P < 0.001), ΔADCmin (P = 0.021), and ΔADCmean (P = 0.022). No lesion showed PD at EOT. CONCLUSIONS Both quantitative interim F-FDG PET and interim DWI may possibly be useful to predict complete remission at end-of-treatment in MALT lymphoma patients after immunotherapy.

Purpose To assess the influence of reconstruction algorithms for positron emission tomography (PET) based volume quantification. The specifically detected activity in the threshold defined volume was investigated for different reconstruction algorithms as a function of volume size and signal to background ratio (SBR), especially for volumes smaller than 1 ml. Special attention was given to the Siemens specific iterative reconstruction algorithm TrueX. Methods Measurements were performed with a modified in-house produced IEC body phantom on a Siemens Biograph 64 True Point PET/CT scanner (Siemens, Medical Systems) for six different SBRs (2.1, 3.8, 4.9, 6.7, 8.9, 9.4 and without active background (BG)). The phantom consisted of a water-filled cavity with built-in plastic spheres (0.27, 0.52, 1.15, 2.57, 5.58 and 11.49 ml). The following reconstruction algorithms available on the Siemens Syngo workstation were evaluated: Iterative OSEM (OSEM) (4 iterations, 21 subsets), iterative TrueX (TrueX) (4 iterations, 21 subsets) and filtered backprojection (FBP). For the threshold based volume segmentation the software Rover (ABX, Dresden) was used. Results For spheres larger than 2.5 ml a constant threshold (standard deviation (SD) 10%) level was found for a given SBR and reconstruction algorithm and therefore a mean threshold for the largest three spheres was calculated. This threshold could be approximated by a function inversely proportional to the SBR. The threshold decreased with increasing SBR for all sphere sizes. For the OSEM algorithm the threshold for small spheres with 0.27, 0.52 and 1.15 ml varied between 17% and 44% (depending on sphere size). The threshold for the TrueX algorithm was substantially lower (up to 17%) than for the OSEM algorithm for all sphere sizes. The maximum activity in a specific volume yielded the true activity for the OSEM algorithm when using a SBR independent correction factor C, which depended on sphere size. For the largest three volumes a constant factor C = 1.10 ± 0.03 was found. For smaller volumes, C increased exponentially due to the partial volume effect. For the TrueX algorithm the maximum activity overestimated the true activity. Conclusion The threshold values for PET based target volume segmentation increased with increasing sphere size for all tested algorithms. True activity values of spheres in the phantom could be extracted using experimentally determined correction factors C. The TrueX algorithm has to be used carefully for quantitative comparison (e.g. follow-up) and multicenter studies.

Introduction Recently, first applications of microfluidic principles for radiosyntheses of positron emission tomography compounds were presented, but direct comparisons with conventional methods were still missing. Therefore, our aims were (1) the set-up of a microfluidic procedure for the preparation of the recently developed adenosine A 3 -receptor tracers [ 18 F]FE@SUPPY [5-(2-[ 18 F]fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate] and [ 18 F]FE@SUPPY:2 [5-ethyl-2,4-diethyl-3-((2-[ 18 F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate] and (2) the direct comparison of reaction conditions and radiochemical yields of the no-carrier-added nucleophilic substitution with [ 18 F]fluoride between microfluidic and conventional methods. Methods For the determination of optimal reaction conditions within an Advion NanoTek synthesizer, 5–50 μl of precursor and dried [ 18 F]fluoride solution were simultaneously pushed through the temperature-controlled reactor (26°C–180°C) with defined reactant bolus flow rates (10–50 μl/min). Radiochemical incorporation yields (RCIYs) and overall radiochemical yields for large-scale preparations were compared with data from conventional batch-mode syntheses. Results Optimal reaction parameters for the microfluidic set-up were determined as follows: 170°C, 30-μl/min pump rate per reactant (reaction overall flow rate of 60 μl/min) and 5-mg/ml precursor concentration in the reaction mixture. Applying these optimized conditions, we observed a significant increase in RCIY from 88.2% to 94.1% ( P n ≥11) for [ 18 F]FE@SUPPY and that from 42.5% to 95.5% ( P n ≥5) for [ 18 F]FE@SUPPY:2 using microfluidic instead of conventional heating. Precursor consumption was decreased from 7.5 and 10 mg to 1 mg per large-scale synthesis for both title compounds, respectively. Conclusion The direct comparison of radiosyntheses data applying a conventional method and a microfluidic approach revealed a significant increase of RCIY using the microfluidic approach.

Introduction Carboxylesterases (CES) play a very important role in the hydrophilic biotransformation of a huge number of structurally diverse drugs and especially play a leading part in the catabolic pathway of carboxylesters or thioesters. Hence, the aim of the present study was the comparison of the in vitro stability of methyl- and ethylesters with fluoroethylesters. Methods We incubated methyl 3β-(4-iodophenyl)tropane-2β-carboxylate (β-CIT)/2-fluoroethyl 3β-(4-iodophenyl)tropane-2β-carboxylate (FE@CIT), methyl 1-(1-phenylethyl)-1 H -imidazole-5-carboxylate (MTO)/ethyl 1-(1-phenylethyl)-1 H -imidazole-5-carboxylate (ETO)/2-fluoroethyl 1-(1-phenylethyl)-1 H -imidazole-5-carboxylate (FETO), ethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4 H -benzo-[f]imidazo[1,5-a]-[1,4]diazepine-3-carboxylate (FMZ)/2-fluoroethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4 H -benzo-[f]imidazo[1,5-a]-[1,4]diazepine-3-carboxylate (FFMZ), methyl 1-phenylethyl-4-( N -propanoylanilino)piperidine-4-carboxylate (CFN)/2-fluoroethyl 1-phenylethyl-4-( N -propanoylanilino)piperidine-4-carboxylate (FE@CFN) and methyl 2,4-diethyl-3-methylsulfanylcarbonyl-6-phenylpyridine-5-carboxylate [(Me) 2 @SUPPY]/2-fluorethyl 2,4-diethyl-3-ethylsulfanylcarbonyl-6-phenylpyridine-5-carboxylate (FE@SUPPY) under physiological conditions. The enzymatic reactions were stopped at different time points and analyzed by a standard protocol. Results The Michaelis–Menten constants ( K M ) and limiting velocities ( V max ) are comparable. The statistical K M values were as follows: β-CIT/FE@CIT, P >.05; MTO/FETO, P >.06; ETO/FETO, P >.09; FMZ/FFMZ, P >.05; CFN/FE@CFN, P >.9; (Me) 2 @SUPPY/FE@SUPPY, P >.07. Conclusion We found no statistical difference in stability against CES in vitro. These findings support the strategy to translate C-11-methyl-/ethylesters into their longer-lived F-18-fluoroethyl analogues.

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 (18)F-fluoroazomycin-arabinoside ((18)FAZA ).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 cm(3) (+/- 67, SD). Dynamic and static (18)FAZA -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.Five patients had visually identifiable tumours on (18)FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five (18)FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten (18)FAZA-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).PET imaging with (18)FAZA 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 (18)FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance.

Objective The authors report imaging findings in a series of 16 patients with MCC, a rare tumour which is often managed primarily by a dermatologist. To our knowledge, no equivalent series of MCC has been described in the nuclear medicine literature. Material and Methods In this IRB-approved retrospective noncomparative case series 16 patients with biopsy-proven Merkel cell carcinoma were included between January 1999 and October 2007. Twenty-nine whole body PET scans (18F-FDG n = 24, 18F-FDOPA n = 5) in 16 patients were retrospectively reviewed with regard to tracer uptake in six anatomical sites per patient. For 127/144 of FDG-PET evaluated regions and 68/144 of regions depicted by conventional imaging methods, a valid standard of reference could be obtained. A combined standard of reference was applied, which consisted of histopathology (lymphadenectomy or biopsy) or clinical or radiological follow-up for at least 12 months. Results: the mean FDG uptake over the clinicopatholigical verified FDG avid areas was 4.7 SUV (1.5–9.9 SUV). The region based assessment of diagnostic value, in consideration of the standard of reference, resulted in a sensitivity of 85.7% and a specificity of 96.2% of FDG-PET (n = 127) and in a combined sensitivity of 95.5% and a specificity of 89.1% for morphological imaging methods (n = 68). Differences between methods did not reach statistical significance (p = 1.00, p = 0.18). Conclusions FDG-PET is a highly useful whole body staging method of comparable value compared to conventional imaging methods with restricted field of view. The lessons learned from case series are discussed.

Objectives: Various studies indicate that serotonin regulates impulsivity and the inhibitory control of aggression. Aggression is also known to be modified by sex hormones, which exert influence on serotonergic neurotransmission. The present study aimed to elucidate potential interactions between human aggression, the inhibitory serotonergic 5‐HT(1A) receptor, and sex hormones. Experimental Design: Thirty‐three healthy volunteers (16 women, aged 26.24 ± 5.5 yr) completed a validated questionnaire incorporating five dimensions of aggression. Subsequently, all subjects underwent positron emission tomography with the radioligand [carbonyl‐(11)C]WAY‐100635 to quantify 5‐HT(1A) binding potentials (BP(ND)s) in the prefrontal cortex, limbic areas, and midbrain. Also, plasma levels of testosterone, 17ß‐estradiol and sex hormone‐binding globulin (SHBG) were measured. Relations between aggression scores, regional 5‐HT(1A) BP(ND)s, and hormone levels were analyzed using correlations, multivariate analyses of variance, and linear regressions. Principal Observations: Statistical analyses revealed higher 5‐HT(1A) receptor BP(ND)s in subjects exhibiting higher aggression scores in prefrontal (all P < 0.041) and anterior cingulate cortices (P = 0.016). More aggressive subjects were also characterized by lower SHBG levels (P = 0.015). Moreover, higher SHBG levels were associated with lower 5‐HT(1A) BP(ND)s in frontal (P = 0.048) and cingulate cortices (all P < 0.013) and in the amygdala (P = 0.03). Conclusions: The present study provides first‐time evidence for a specific interrelation between the 5‐HT(1A) receptor distribution, sex hormones, and aggression in humans. Our findings point to a reduced down‐stream control due to higher amounts or activities of frontal 5‐HT(1A) receptors in more aggressive subjects, which is presumably modulated by sex hormones. Hum Brain Mapp 30:2558–2570, 2009. © 2008 Wiley‐Liss, Inc.

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-HT(1A)) receptor.Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [carbonyl-(11)C]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-HT(1A) receptor BP(ND) 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-HT(1A) receptor BP(ND) was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BP(ND) 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-HT(1A) receptor BP(ND) 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-HT(1A) 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-HT(1A) receptor expression.

Introduction Changes of the adenosine A 3 receptor subtype (A3AR) expression have been shown in a variety of pathologies, especially neurological and affective disorders, cardiac diseases and oncological and inflammation processes. Recently, 5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (FE@SUPPY) was presented as a high-affinity ligand for the A3AR with good selectivity. Our aims were the development of a suitable labeling precursor, the establishment of a reliable radiosynthesis for the fluorine-18-labeled analogue [ 18 F]FE@SUPPY and a first evaluation of [ 18 F]FE@SUPPY in rats. Methods [ 18 F]FE@SUPPY was prepared in a feasible and reliable manner by radiofluorination of the corresponding tosylated precursor. Biodistribution was carried out in rats, and organs were removed and counted. Autoradiography was performed on rat brain slices in the presence or absence of 2-Cl-IB-MECA. Results Overall yields and radiochemical purity were sufficient for further preclinical and clinical applications. The uptake pattern of [ 18 F]FE@SUPPY found in rats mainly followed the described mRNA distribution pattern of the A3AR. Specific uptake in brain was demonstrated by blocking with a selective A3AR agonist. Conclusion We conclude that [ 18 F]FE@SUPPY has the potential to serve as the first positron emission tomography tracer for the A3AR.

Pregraduate medical curricula are currently undergoing a reform process that is moving away from a traditional discipline-related structure and towards problem-based integrated forms of teaching. Imaging sciences, with their inherently technical advances, are specifically influenced by the effects of paradigm shifts in medical education. The teaching of diagnostic radiology should be based on the definition of three core competencies: in vivo visualization of normal and abnormal morphology and function, diagnostic reasoning, and interventional treatment. On the basis of these goals, adequate teaching methods and e-learning tools should be implemented by focusing on case-based teaching. Teaching materials used in the fields of normal anatomy, pathology, and clinical diagnosis may help diagnostic radiology to play a central role in modern pregraduate curricula.

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.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.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).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.

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.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.[(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).[(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.

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.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.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.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.

SummaryMetabolic imaging with 2-[fluorine-18]-fluoro- 2-deoxy-D-glucose (FDG) is actually considered as the best method to detect and quantitatively assess myocardial tissue viability. The aim of this study was to investigate the accuracy of FDG gamma camera positron emission tomography (GCPET) imaging equipped with one inch NaI crystals in comparison to FDG dedicated PET (dPET) imaging as a „gold standard“ in phantom and clinical studies. Patients, methods: Nineteen patients with coronary artery disease (CAD) underwent both imaging modalities. Phantom and clinical GCPET imaging were performed with a dual-headed, coincidence based gamma camera equipped with 1 inch thick NaI crystals and an x-ray tube (XCT) for attenuation correction (AC), as well as with a dedicated PET scanner with AC. 99mTc tetrofosmin single-photon emission tomography (SPET) studies were performed for assessment of myocardial perfusion, with AC. Results: Phantom studies showed a significant relation in segmental activity between FDG imaging with AC using GCPET and dPET (r = 0.91, p

A one-pot radiosynthesis method to prepare the new fluorine-18-labelled fluoropyridine derivatives 5-[18F]fluoro-2-pyridinamine and 6-[18F]fluoro-2-pyridinamine in two to three reaction steps was developed. The first step consisted of no-carrier-added nucleophilic aromatic substitution of commercially available halogen-substituted 2-pyridinecarboxamide or 2-pyridinecarbonitrile derivatives with K[18F]F-K222 in DMSO at 150–180°C. The [18F]fluoride incorporation yields ranged from 67 to 98% for all studied precursor molecules. It is remarkable that 5-bromo-2-pyridinecarbonitrile gave almost quantitative [18F]fluoride incorporation at the meta-position (5-position) of the pyridine ring after only 5 min of heating at 150°C. After base-catalysed hydrolysis of the [18F]fluorinated pyridinecarbonitriles into their corresponding carboxamides, the latter were transformed in a Hofmann-type rearrangement reaction into the respective amines by treatment of crude reaction mixtures with bromine and aqueous base (20–30% conversion yield). Reaction mixtures were purified by reversed-phase semipreparative HPLC followed by strong cation exchange solid-phase extraction to afford 5-[18F]fluoro-2-pyridinamine and 6-[18F]fluoro-2-pyridinamine in non-decay-corrected radiochemical yields of 6–10% in a total synthesis time of 83–112 min. The preparation of 5-[18F]fluoro-2-pyridinamine is one of very few examples demonstrating the feasibility of nucleophilic meta-[18F]fluorination of a pyridine derivative. Both 5-[18F]fluoro-2-pyridinamine and 6-[18F]fluoro-2-pyridinamine are new potentially useful radiolabelled synthons for radiopharmaceutical chemistry. Copyright © 2006 John Wiley & Sons, Ltd.

In advanced seminoma the management of residuals after completion of chemotherapy is controversial. Some centres routinely perform surgery for lesionsor =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.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 (oror =3 cm) of the residual masses.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 lesions3 cm and 11/27 lesionsor =3 cm were viable. PET was true positive in one lesion3 cm and in 11 lesionsor =3 cm, false negative in three lesions3 cm, and true negative in 59 lesions (43 lesions3 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 (oror =3 cm); and 80% (51-95), and 100% (93-100), respectively, for PET (specificity, P0.001).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 aor =3 cm cut-off. A negative PET scan is excellent for the exclusion of disease in lesionsor =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 lesionsor =3 cm.

1,1′-Methylene-di-(2-naphthol) (ST1859), a candidate drug for the treatment of Alzheimer's disease, was radiolabelled with carbon-11 with the aim to perform PET microdosing studies in humans. The radiosynthesis was automated in a commercial synthesis module (Nuclear Interface PET tracer synthesizer) and proceeded via reaction of [11C]formaldehyde with 2-naphthol. [11C]formaldehyde was prepared by catalytic dehydrogenation of [11C]methanol (conversion yield: 48±11% (n = 19)) employing a recently developed silver-containing ceramic catalyst. Starting from 69±3 GBq of [11C]carbon dioxide (n = 19), 4±1 GBq of [11C]ST1859 (decay-corrected to the end of bombardment), readily formulated for intravenous administration, could be obtained in an average synthesis time of 38 min. The specific radioactivity of [11C]ST1859 at the end of synthesis exceeded 32 GBq/µmol. Copyright © 2005 John Wiley & Sons, Ltd.

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.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.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.Taken together, our results indicate that [18F]ciprofloxacin is not suited as a bacteria-specific infection imaging agent for PET.

[(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.

Recently, two fluorine-18 labelled derivatives of flumazenil were described: 5-(2′-[18F]fluoroethyl)-5-desmethylflumazenil (ethyl 8-fluoro-5-[18F]fluoroethyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a] [1,4]diazepine-3-carboxylate; [18F]FEFMZ) and 3-(2′-[18F]fluoro)-flumazenil (2′-[18F]fluoroethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a]-[1,4]diazepine-3-carbo- xylate; [18F]FFMZ). Since the biodistribution data of the latter were superior to those of the former we developed a synthetic approach for [18F]FFMZ starting from a commercially available precursor, thereby obviating the need to prepare a precursor by ourselves. The following two-step procedure was developed: First, [18F]fluoride was reacted with 2-bromoethyl triflate using the kryptofix/acetonitrile method to yield 2-bromo-[18F]fluoroethane ([18F]BFE). In the second step, distilled [18F]BFE was reacted with the tetrabutylammonium salt of 3-desethylflumazenil (8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a] [1,4]diazepine-3-carboxylic acid) to yield [18F]FFMZ. The synthesis of [18F]FFMZ allows for the production of up to 7 GBq of this PET-tracer, enough to serve several patients. [18F]FFMZ synthesis was completed in less than 80 min and the radiochemical purity exceeded 98%. Copyright © 2003 John Wiley & Sons, Ltd.

Fluoroquinolones are an important class of antibiotic agents with a broad spectrum of antibacterial activity. Labelling of fluoroquinolones with fluorine-18 is of interest for the performance of pharmacokinetic measurements and the visualization of bacterial infections in humans with positron emission tomography. A two-step radiosynthetic pathway to prepare fluorine-18-labelled ciprofloxacin (1-cyclopropyl-6-[18F]fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid) has previously been developed. In the present work this approach was applied to the preparation of the structurally related compounds [18F]norfloxacin (1-ethyl-6-[18F]fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid) and [18F]pefloxacin (1-ethyl-6-[18F]fluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-quinoline-3-carboxylic acid). The first step of the radiosynthesis consisted of a 18F for 19F exchange reaction on a 7-chloro-substituted precursor molecule, followed by coupling reactions with the amines piperazine or 1-methylpiperazine. Starting from 51–58 GBq of [18F]fluoride 1.9–2.0 GBq of [18F]norfloxacin or [18F]pefloxacin, ready for intravenous injection, could be obtained in a synthesis time of 130 min (3.5–3.8% overall radiochemical yield). Moreover, the preparation of [18F]levofloxacin ((-)-(S)-9-[18F]fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylicacid) was attempted but failed to afford the desired product in practical amounts. Copyright © 2003 John Wiley & Sons, Ltd.

Ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid), a widely-prescribed antibiotic, was labeled with fluorine-18 with the aim to perform positron emission tomography studies in humans for pharmacokinetic measurements. Due to a lack of chemical activation of ciprofloxacin for a direct nucleophilic exchange reaction a novel two-step synthetic approach, which employed an activated 6-fluoro-7-chloro substituted precursor molecule, was developed. The radiosynthesis yielded, starting from 52.5 ± 11.3 GBq of [ 18 F]fluoride, 1.3 ± 0.6 GBq (n = 13) [ 18 F]ciprofloxacin ready for intravenous administration in about 130 min synthesis time. A series of analytical tests was performed in order to prove the identity of the radiolabeled compound and its suitability for human applications.

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

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for follow-up.

Zusammenfassung Tomographische Rekonstruktionsmethoden fur die Positronen-Emissions-Tomographie lassen sich in zwei grose Klassen einteilen: Neben der traditionell verwendeten gefilterten Ruckprojektion werden auf statistischen Modellen beruhende iterative Algorithmen eingesetzt. In dieser Arbeit wird die Leistungsfahigkeit unterschiedlicher Algorithmen zur Bildrekonstruktion durch Anwendung objektiver Evaluierungskriterien abseits rein visueller Beurteilungsmasstabe verglichen. Als Vergleichskriterien werden die Bildparameter mittlerer quadratischer Fehler, Standardabweichung, Signal-zu-Rausch-Verhaltnis und Kontrastwiedergabe-Vermogen verwendet. Als Rekonstruktionsmethoden stehen die klassische gefilterte Ruckprojektion, der Maximum Likelihood Expectation Maximization-Algorithmus, die zur Gruppe der Bayesschen Verfahren gehorige Maximum a-Posteriori-Methode und Beschleunigungsalgorithmen basierend auf der Verwendung von Ordered Subsets und High Overrelaxation Parameter zur Verfugung. Diese Algorithmen werden anhand eines mathematischen Hirnphantoms und eines physikalischen Kugelphantoms evaluiert. Die Mehrzahl der durchgefuhrten Experimente zeigt eine in den verwendeten Parametern quantifizierbare Uberlegenheit der iterativen Methoden gegenuber der gefilterten Ruckprojektion.

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.

Poorly differentiated insular thyroid carcinoma is now classified as a separate entity among other tumors of the thyroid gland. Its histologic pattern and its clinical course are regarded as intermediate between well differentiated and anaplastic thyroid cancer. Insular carcinoma accumulates I-131, but no data exist regarding its fluorodeoxyglucose (FDG) positron emission tomographic (PET) uptake. The authors report F-18 FDG PET, Tc-99m MIBI, and radioiodine imaging features in a 63-year-old patient with metastatic insular thyroid carcinoma. After total thyroidectomy (for poorly differentiated insular carcinoma pT3a), the patient was referred for radioiodine ablation. No signs of recurrence were present until 16 months later, when thyroglobulin levels increased. An I-131 scan showed a single lesion in the right lung, and further radioiodine treatment was administered (cumulative dose [530 mCi], 19,610 MBq I-131). Three years after the initial diagnosis, FDG-PET and Tc-99m MIBI scans were performed within 5 days during thyroxine treatment. After that, thyroxine substitution was withdrawn; 6 weeks later, an I-131 whole-body scan was performed. Both radioiodine and MIBI images showed increased tracer uptake in the known lung lesion. However, FDG PET showed a normal tracer distribution. Magnetic resonance and computed tomographic imaging confirmed a 12-mm lesion in the right upper lobe. These findings support the concept of the "flip-flop phenomenon" in insular thyroid carcinoma, an alternating pattern of metastases with either I-131 or FDG-uptake. Despite poorly differentiated histologic findings, glucose metabolism was not increased in this patient with an insular tumor.

Introduction Recently, [ 18 F]FE@SUPPY and [ 18 F]FE@SUPPY:2 were introduced as the first positron emission tomography (PET) tracers for the adenosine A 3 receptor. Thus, aim of the present study was the metabolic characterization of the two adenosine A 3 receptor PET tracers. Methods In vitro carboxylesterase (CES) experiments were conducted using incubation mixtures containing different concentrations of the two substrates, porcine CES and phosphate-buffered saline. Enzymatic reactions were stopped by adding acetonitrile/methanol (10:1) after various time points and analyzed by a high-performance liquid chromatography (HPLC) standard protocol. In vivo experiments were conducted in male wild-type rats; tracers were injected through a tail vein. Rats were sacrificed after various time points ( n =3), and blood and brain samples were collected. Sample cleanup was performed by an HPLC standard protocol. Results The rate of enzymatic hydrolysis by CES demonstrated Michaelis–Menten constants in a micromolar range (FE@SUPPY, 20.15 μM, and FE@SUPPY:2, 13.11 μM) and limiting velocities of 0.035 and 0.015 μM/min for FE@SUPPY and FE@SUPPY:2, respectively. Degree of metabolism in blood showed the following: 15 min pi 47.7% of [ 18 F]FE@SUPPY was intact compared to 33.1% of [ 18 F]FE@SUPPY:2; 30 min pi 30.3% intact [ 18 F]FE@SUPPY was found compared to 15.6% [ 18 F]FE@SUPPY:2. In brain, [ 18 F]FE@SUPPY:2 formed an early hydrophilic metabolite, whereas metabolism of [ 18 F]FE@SUPPY was not observed before 30 min pi Conclusion Knowing that metabolism in rats is several times faster than in human, we conclude that [ 18 F]FE@SUPPY should be stable for the typical time span of a clinical investigation. As a consequence, from a metabolic point of view, one would tend to decide in favor of [ 18 F]FE@SUPPY.

Tariquidar, a potent, nontoxic, third-generation P-glycoprotein (P-gp) inhibitor, is a possible reversal agent for central nervous system drug resistance. In animal studies, tariquidar has been shown to increase the delivery of P-gp substrates into the brain by severalfold. The aim of this study was to measure P-gp function at the human blood-brain barrier (BBB) after tariquidar administration using PET and the model P-gp substrate (R)-(11)C-verapamil. METHODS: Five healthy volunteers underwent paired (R)-(11)C-verapamil PET scans and arterial blood sampling before and at 2 h 50 min after intravenous administration of tariquidar (2 mg/kg of body weight). The inhibition of P-gp on CD56-positive peripheral lymphocytes of each volunteer was determined by means of the (123)Rh efflux assay. Tariquidar concentrations in venous plasma were quantified using liquid chromatography/mass spectrometry. RESULTS: Tariquidar administration resulted in significant increases (Wilcoxon test for paired samples) in the distribution volume (DV, +24% +/- 15%) and influx rate constant (K(1), +49% +/- 36%) of (R)-(11)C-verapamil across the BBB (DV, 0.65 +/- 0.13 and 0.80 +/- 0.07, P = 0.043; K(1), 0.034 +/- 0.009 and 0.049 +/- 0.009, P = 0.043, before and after tariquidar administration, respectively). A strong correlation was observed between the change in brain DV after administration of tariquidar and tariquidar exposure in plasma (r = 0.90, P = 0.037). The mean plasma concentration of tariquidar achieved during the second PET scan (490 +/- 166 ng/mL) corresponded to 100% inhibition of P-gp function in peripheral lymphocytes. CONCLUSION: Tariquidar significantly increased brain penetration of (R)-(11)C-verapamil-derived activity due to increased influx. As opposed to peripheral P-gp function, central P-gp inhibition appeared to be far from complete after the administered tariquidar dose.

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood–brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. Methods: A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). Results: After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 ± 0.81 vs. 0.30 ± 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose–response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 ± 9.5 mg/kg. Conclusion: Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.

Purpose (R)-[C-11]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[C-11]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[C-11]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers.Methods Arterial blood samples were collected from eight patients undergoing (R)-[C-11]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[C-11]verapamil by using an assay that measures polar N-demethylation metabolites by solid-phase extraction and lipophilic N-dealkylation metabolites by HPLC.Results Peripheral metabolism of (R)-[C-11]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R)-[C-11]verapamil fraction in plasma: 29.4 +/- 3.9 min for patients versus 40.8 +/- 5.0 min for healthy volunteers; p Conclusions Faster metabolism of (R)-[C-11]verapamil in epilepsy patients may be caused by hepatic cytochrome P450 enzyme induction by antiepileptic drugs. Based on these data caution is warranted when using an averaged arterial input function derived from healthy volunteers for the analysis of patient data. Moreover, our data illustrate how antiepileptic drugs may decrease serum levels of concomitant medication, which may eventually lead to a loss of therapeutic efficacy.

Since the late 1980s, cocaine analogues based on the phenyltropane structure, such as [(11)C]CFT and [(123)I]beta-CIT have been used for the imaging of the dopamine transporter. FE@CIT (fluoropropyl ester) and FP-CIT (N-fluoropropyl derivative) are further analogues. The aim of this study was to (1) evaluate and compare the metabolic stability of beta-CIT, FP-CIT and FE@CIT against carboxyl esterases and (2) evaluate selectivity of [(18)F]FE@CIT compared to [(123)I]beta-CIT and [(123)I]FP-CIT using autoradiography.In vitro enzymatic hydrolysis assays were performed using different concentrations of beta-CIT, FE@CIT and FP-CIT with constant concentrations of carboxyl esterase. Autoradiography was performed on coronal 20-microm rat brain sections incubated with different radioactivity concentrations of [(123)I]beta-CIT, [(123)I]FP-CIT or [(18)F]FE@CIT and, additionally, with 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile [serotonin transporter (SERT)] and nisoxetine [norepinephrine transporter (NET)] for blocking experiments.In vitro assays showed Michaelis-Menten constants of 175 micromol (beta-CIT), 183 micromol (FE@CIT) and 521 micromol (FP-CIT). Limiting velocities were 0.1005 micromol/min (beta-CIT), 0.1418 micromol/min (FE@CIT) and 0.1308 micromol/min (FP-CIT). This indicates a significantly increased stability of FP-CIT, whereas carboxyl esterase stability of beta-CIT and FE@CIT showed no significant difference. Autoradiographic analyses revealed a good correlation between dopamine transporter (DAT)-rich regions and the uptake pattern of FE@CIT. Blocking experiments showed a higher DAT selectivity for [(18)F]FE@CIT than for the other two tracers.We found that (1) the metabolic stability of FE@CIT was comparable to that of beta-CIT, whereas FP-CIT showed higher resistance to enzymatic hydrolysis; and (2) the overall uptake pattern of [(18)F]FE@CIT on brain slices was comparable to that of [(123)I]beta-CIT and [(123)I]FPCIT. After blocking of NET and SERT binding, a significantly higher DAT selectivity was observed for [(18)F]FE@CIT. Hence, [(18)F]FE@CIT may be of interest for further clinical application.

Introduction The translation of 11 C-labeled compounds into their respective 18 F-labeled derivatives is an important tool in the rapid development of positron emission tomography (PET) tracers. Thus, our aim was the development of a general method for the preparation of 18 F-fluoroethylated compounds that (a) is applicable to a variety of precursors, (b) can be performed in a fully automated commercially available synthesizer and (c) enables this rapid translation of 11 C-methylated tracers into their 18 F-fluoroethylated analogs sharing the same precursor molecules. Methods Ten methods for the preparation and purification of different 18 F-fluoroethylating agents were compared. Subsequently, five 18 F-labeled PET tracers were synthesized under fully automated conditions. Results Radiochemical yields ranged from 34.4% to 60.8%, and time consumption ranged from 20 to 55 min for all methods. Use of 1-bromo-2-[ 18 F]fluoroethane and distillation evinced as the method of choice. Conclusions We were able to develop a general method for the preparation of a variety of 18 F-fluoroethylated molecules. The provided tool is solely based on commercially available resources and has the potential to simplify and accelerate innovative PET tracer development in the future.

Introduction The objectives of this study were to develop a simple preparation method for [ 68 Ga]-EDTMP and to evaluate the applicability of [ 68 Ga]-EDTMP as a potential positron emission tomography (PET) bone imaging agent using pre vivo, ex vivo and in vivo models. Methods [ 68 Ga]-EDTMP was prepared using [ 68 Ga]-gallium chloride eluted from the 68 Ge/ 68 Ga generator and commercially available Multibone kits. Binding affinity to bone compartments was evaluated using a recently established pre vivo model. In vivo (microPET) and ex vivo experiments were performed in mice, and the results of which were compared with those obtained with [ 18 F]-fluoride. Results [ 68 Ga]-EDTMP was accessible via simple kit preparation and predominantly accumulated in bone tissue in vivo, ex vivo and pre vivo. Binding to mineral bone was irreversible, and low binding was observed in organic bone. In vivo microPET evaluation revealed predominant uptake in bone with renal excretion. Compared with [ 18 F]-fluoride, the uptake was lower and the PET image quality was reduced. Conclusions From the present evaluation, apart from the autonomy for PET centers without an onsite cyclotron, the advantage of [ 68 Ga]-EDTMP over [ 18 F]-fluoride is not apparent and the future clinical prospect of [ 68 Ga]-EDTMP remains speculative.

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.

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).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).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.

(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.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).MTO imaging clearly distinguished cortical from non-cortical adrenal masses (median standardised uptake values of 18.6 and 1.9, respectively, p0.01). 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.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.

Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[(18)F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean+/-SD), were 2.05+/-0.91 for MET and 2.04+/-0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of (18)F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging.

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.

Planar scintimammography (SMM) with 99 Tc m -sestamibi ( 99 Tc m -MIBI) has proved to be a useful method in the evaluation of breast lesions. The aim of our study was to determine the diagnostic value of planar and single photon emission tomograpic (SPET) SMM in different age groups. We investigated women with breast lesions for which the surgeon recommended biopsy or careful follow-up. Seventy consecutive patients underwent supine planar SMM, while supine SPET was performed in 68 of the patients. Twenty-seven carcinomas in 23 patients and 35 benign lesions in 31 patients were confirmed histologically. In the remaining 16 patients, the findings were classified as benign at follow-up. The carcinomas and benign lesions had a mean (± s.D.) diameter of 25 ± 17 and 17 ± 11 mm respectively (P < 0.05). A sensitivity/ specificity of 67/96% and 88/91% was obtained with the planar and SPET techniques respectively. The accuracy of both techniques was 90%. In patients aged 40 years or less, SPET increased the sensitivity from 50 to 100% (P < 0.01), whereas it decreased the specificity and accuracy from 94 to 81% and 91 to 81% respectively (N.s.). In patients aged 41-50 years, the sensitivity increased from 63 to 100% (P < 0.01), whereas there was a small decrease in specificity and an increase in accuracy (from 91 to 89% and 86 to 91% respectively; N.S.). We conclude that, in younger patients, a negative SPET SMM study indicates the need for careful follow-up rather than biopsy. However, the addition of SPET in supine scintimammography does not change the overall accuracy significantly.

The aim of this prospective study was to evaluate the diagnostic utility of a technetium-99m sestamibi dual-phase protocol enhanced by single-photon emission tomography (SPET) and semiquantitative analysis in comparison to established preoperative staging procedures in patients with primary hyperparathyroidism. Twenty-eight (50%) out of 56 patients had superimposed thyroid disease, and 12 patients had previously undergone neck surgery. Visual and semiquantitative analysis of planar 99mTc-sestamibi dual-phase imaging, SPET of the delayed phase, ultrasonography, and thallium-201 chloride-technetium-99m pertechnetate subtraction scintigraphy was further correlated with the histopathological examination of the surgical specimens. 99mTc-sestamibi dual-phase imaging achieved the highest sensitivity for side localization and precise localization compared with 201Tl-99mTc subtraction scintigraphy and ultrasonography, but the differences reached statistical significance only in comparison to ultrasonsography. Semiquantitative analysis did not enhance sensitivity. Adenoma detection by 99mTc-sestamibi dual-phase imaging was only correlated to serum calcium levels and osteocalcin, not to cell density or oxyphil cell count (SPET yielded additional information for the exact topographical localization of the parathyroid tumour in 22 (39%) patients with superimposed thyroid disease or previous neck surgery but did not enhance the overall detection rate.

Cutaneous recurrence after resection of gastric cancer is relatively rare. The authors describe a patient with cutaneous metastasis as the first sign of relapse 4 months after resection of a primary gastric cancer. F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) was performed after normal results were obtained with conventional staging and revealed a cutaneous metastasis on the patient's back and a second cutaneous lesion in the abdominal wall, which were verified by biopsy. In addition, the F-18 FDG-PET images disclosed abdominal lymph node involvement. This case illustrates the ability of F-18 FDG PET to detect metastatic tumor spread in unexpected sites as clinically inapparent cutaneous metastases in gastric cancer.

Purpose. Tc-99m tetrofosmin launched for myocardial studies has recently also shown a good detectability for several tumors. Data on PNET imaging by Tc-99m tetrofosmin are not yet available. Patient and method. In the case of a 21-year-old man suffering from pelvis PNET, Tc-99m tetrofosmin scintigraphy was performed additionally to CT and MRI. Results. The gluteal and iliac tumor masses were visualized by Tc-99m tetrofosmin according to the CT and MRI results. Discussion. Imaging with Tc-99m tetrofosmin could provide additional information to the available conventional radiological imaging modalities for diagnosis of PNET, and could be a useful tool for the restaging of the primary tumor.

The aim of the study was to determine the practicability of 18F-FLT in tumours of the head and neck area in terms of visualization, a possible correlation between FLT uptake and proliferation fraction as determined by Ki-67 immunostaining, and if tumoural FLT-uptake has a prognostic meaning, as determined by a correlation to patient survival time. Results were compared to 18F-FDG. Patients, methods: 20 patients with previously untreated lesions of the head and neck area, which were clinically highly suspicious to be malignant, underwent PET scans with 18F-FLT and 18F-FDG, a CT of the head and neck area, and a biopsy. Tumour tracer uptake was determined by standardized uptake value (SUV) normalized to body weight and /non-tumor ratios (T/N). 18F-FDG and 18F-FLT uptake were compared with histopathologic and immunohistochemical results. Results: 19 patients had malignant tumours; one patient had a benign cystadenoma (so called Warthin’s tumour) of the parotid gland. One negative lesion turned out to be a malignant T1 stage squamous cell carcinoma in both PET scans, the Warthin's tumour was false positive with 18F-FDG but showed only faint uptake with 18F-FLT, resulting in a sensitivity of 95 % for both tracers. Of all lesions, maximum SUVs of 18F-FLT ranged from 1.53 to 11.70 (mean ± SD 5.81 ± 2.28) those of FDG from 2.63 to 16.50 (mean ± SD 8.91 ± 3.58), p < 0.001. 18F-FLT-T/N ranged from 0.94 to 5.85 (mean ± SD, 3.18 ± 1.21), 18F-FDG-T/N was from 0.92 to 7.50 (mean ± SD, 3.6 ± 1.74), n.s. The mean survival time was 18 months in a maximum follow up time of 36 months. A significant correlation between both PET tracers and survival was detected, but no correlation between the amount of Ki-67 positive cells and FLT. Conclusion: In head and neck cancer in the primary setting 18F-FLT does not provide additional visual information in comparison to 18F-FDG.18F-FLT uptake is inversely correlated with patient survival, as well as 18F-FDG.