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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]

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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]

Abstract: Functional information provided by PET tracers together with the superior image quality and the better data quantification by PET technology had a changing effect on the significance of nuclear medicine in medical issues. Recently introduced hybrid PET/CT systems together with the introduction of novel PET radiopharmaceuticals have contributed to the fact that nuclear medicine has become a growing diagnostic impact on endocrinology. In this review imaging strategies, different radiopharmaceuticals including the basic mechanism of their cell uptake, and the diagnostic value of PET and PET/CT in endocrine tumours except differentiated thyroid carcinomas will be discussed. [Copyright &y& Elsevier]

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]

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]

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: 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: 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]

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]

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]

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]

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]

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 article reports on imaging of adrenocortical metastases with the 11 β-hydroxylase inhibitor [11C]metomidate. It presents a positron emission tomography images taken from a 50-year-old patient with metastatic adrenocortical carcinoma. The interpretation of the findings are presented.

Abstract: 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 A3-receptor tracers [18F]FE@SUPPY [5-(2-[18F]fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate] and [18F]FE@SUPPY:2 [5-ethyl-2,4-diethyl-3-((2-[18F]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 [18F]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 [18F]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<.0001, n≥11) for [18F]FE@SUPPY and that from 42.5% to 95.5% (P<.0001, n≥5) for [18F]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. [Copyright &y& Elsevier]

Abstract: Introduction: Recently, [18F]FE@SUPPY and [18F]FE@SUPPY:2 were introduced as the first positron emission tomography (PET) tracers for the adenosine A3 receptor. Thus, aim of the present study was the metabolic characterization of the two adenosine A3 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 [18F]FE@SUPPY was intact compared to 33.1% of [18F]FE@SUPPY:2; 30 min pi 30.3% intact [18F]FE@SUPPY was found compared to 15.6% [18F]FE@SUPPY:2. In brain, [18F]FE@SUPPY:2 formed an early hydrophilic metabolite, whereas metabolism of [18F]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 [18F]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 [18F]FE@SUPPY. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Introduction: Changes of the adenosine A3 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 [18F]FE@SUPPY and a first evaluation of [18F]FE@SUPPY in rats. Methods: [18F]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 [18F]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 [18F]FE@SUPPY has the potential to serve as the first positron emission tomography tracer for the A3AR. [Copyright &y& Elsevier]

Abstract: Introduction: The objectives of this study were to develop a simple preparation method for [68Ga]-EDTMP and to evaluate the applicability of [68Ga]-EDTMP as a potential positron emission tomography (PET) bone imaging agent using pre vivo, ex vivo and in vivo models. Methods: [68Ga]-EDTMP was prepared using [68Ga]-gallium chloride eluted from the 68Ge/68Ga 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 [18F]-fluoride. Results: [68Ga]-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 [18F]-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 [68Ga]-EDTMP over [18F]-fluoride is not apparent and the future clinical prospect of [68Ga]-EDTMP remains speculative. [Copyright &y& Elsevier]

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

[11C]Flumazenil, a highly selective benzodiazepine antagonist is the most extensively used GABAA ligand for PET so far. To overcome half life disadvantages of 11C a [18F]-labeled flumazenil derivative, 2′-[18F]fluoroflumazenil (FFMZ) was developed and biologically evaluated with respect to the GABAA 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 [3H]flumazenil binding from membrane GABAA receptors with an IC50value (3.5 nM) comparable to that of Flumazenil (2.8 nM). The presented data confirm the potential of [18F]FFMZ for PET imaging of the GABA-ergic system. [Copyright &y& Elsevier]